Polypharmacy prescribing guidance - draft: consultation

8. Hot topics

8.1 Long-term Conditions

8.1.1 Hot Topic: Chronic pain in adults - the use of opioids, gabapentinoids and antidepressants

What is the aim of this hot topic and therapy?

The aim of this hot topic is to ensure that prescribing analgesics in chronic non-malignant pain is safe, effective with ongoing review to reduce and cease analgesic use where appropriate with a person-centred approach.

Chronic pain, also called persistent pain, is defined as persistent or recurring pain that lasts longer than three months despite medication or treatment and is a recognised long-term condition.^[152]

Moderate to severe chronic pain affects one in five people in Scotland. ^[153] Chronic pain can significantly impact an individual’s quality of life, mood and function. Many people living with pain need to be supported and empowered to manage their pain, considering non-pharmaceutical options in the first instance. This reduces the risk of over-medication and side effects which can increase the risk of adverse effects, especially if there is multimorbidity or frailty. Total eradication of pain is unlikely, and evidence reviews frequently consider an intervention effective if it reduces pain by 30% [154] to 50%. [155]

Individuals should have access to personalised information and support with an awareness that chronic pain is a long-term condition. The goal is increased function and improved quality of life.

Is this an essential medicine?

Opioids are not considered essential medicines, but they should not be stopped abruptly (see later sections). Essential medicines are defined as those that may cause rapid symptomatic decline or loss of disease control if discontinued and that should only be stopped on specialist advice.2

Use of the terms “opiate” and “opioid” can cause confusion. Opiates are naturally occurring alkaloids derived from the opium poppy. Opioids are synthetic drugs which produce an opiate like effect. All act at receptors in the body defined as opioid receptors. For the purposes of this hot topic, the term opioid(s) is used to refer to both opioid and opiate based medicines.

Antidepressants and anticonvulsants may also be prescribed for chronic pain alongside management of depression, epilepsy and other conditions. These conditions need to be carefully considered when altering drug dosages, including the dosage of any opioid medication. Those suffering chronic pain with co-existing depression should have their antidepressant therapy optimised, rather than adding a subsequent antidepressant medication. ^[156]

This hot topic does not consider acute pain, e.g. post-operative; or use in other settings such as palliative care or management of terminal disease, including conditions such as breathlessness in the advanced stages of respiratory disease.

Important benefits and risks of treatment, including any groups where specific considerations are required

General:

Individuals living with pain should feel empowered to self-manage their condition. A person’s experience of pain is influenced by multiple factors. This can include a variety of emotional and psychological factors (e.g. anxiety, distress, depression, previous trauma), in addition to social and biological factors. A concise history, examination and biopsychosocial assessment, identifying pain type (neuropathic/nociceptive/mixed/unknown), severity of pain, functional impact and context should be conducted in all those with chronic pain. This will inform the selection of treatment options most likely to be effective.

It is good practice to establish and record the baseline level of pain experienced and functional capacity for future reference and comparison. Tools to support this are available, e.g. the British Pain Society Pain Rating Scale (and see chronic pain resource section).

Healthcare professionals and individuals should have honest conversations about the role of medication in the management of chronic pain:

• considering the holistic nature of pain
• explaining that analgesia is unlikely to completely eliminate pain but may lessen pain intensity
• there should be an understanding that pain is both a physical and emotional experience, often associated with stress, health beliefs or trauma in their lives
• supported self-management strategies can be more beneficial to overall well-being
• there can be an over reliance on pain medicines as an intervention with unrealistic expectations that there will be complete pain resolution

• therefore, any treatment prescribed should be reviewed regularly and withdrawn if not effective, with individuals supported in taking the minimum dose of medication that results in the maximum benefit to their wellbeing while minimising medication-related harm.

Key areas for consideration include:

• biopsychosocial model of pain
• understanding their diagnosis
• activity management and pacing
• diet and lifestyle
• sleep
• emotions and mood
• value based goal setting
• flare-up planning

Opioids, gabapentinoids and antidepressants are associated with a risk of dependency. [157]^,[158] Individuals should be made aware of risks on initiation and supported to withdraw as appropriate.

Healthcare professionals should be aware of the possibility that some individuals may present with ‘drug seeking behaviour’, due to the potential for addiction and withdrawal reactions from gabapentinoids, opioids and antidepressants. To minimise this risk, they should have honest conversations with people at the onset of prescribing about the limitation of medication for the management of pain (see resources section). Further information about this is also given in section 9.26 in the case study on drug dependency and requests for out of hours medication.

Numbers needed to treat (NNTs) in the management of chronic pain may appear relatively low, e.g. NNT for pregabalin for managing post herpetic neuralgia is four. However, this means that for every one person with reduced pain intensity, there are three people who receive no benefit, with increased risk of adverse effects. Ineffective medication should be safely stopped.

Opioids

Opioids should not be considered routinely for people with chronic non-malignant pain. In carefully selected individuals, when other therapies have been fully explored, opioids can be considered for short-term treatment (up to three months), if it is considered that the potential benefits outweigh the risks of serious harms such as addiction, overdose and death.156^{, [159], [160], [161], [162], [163], [164], [165], [166], [167]}

Benefits:

The benefits of opioids in chronic pain are limited to lower doses for short to medium-term treatment (less than three months).

Risks:

All people on an opioid should have a review of their treatment, prioritising individuals prescribed more than 50mg morphine equivalent dose (MED), who should be reviewed at least annually to consider ongoing effectiveness and potential harms, due to lack of evidence to support long-term use. 156^, [168] See dose equivalence table below.

Opioid dose conversion chart – equivalent to morphine sulfate 10mg orally

There are a variety of opioid dose conversion charts available. Currently the preferred version is the BNF which aligns with the Faculty of Pain Management and Scottish palliative care guidelines. ^[169]

If a different dose conversion is used this should be specified as should the date/version of the conversion used (due to regular updates).

If converting from one opioid to another, individuals should be monitored to assess effectiveness and adverse reactions.

• Note as with all opioid conversions, these are approximate doses
• Dose conversions should be conservative and doses rounded down
• Monitor the individual to assess effectiveness and adverse effects, so that the dose can be adjusted if necessary
• If there is opioid toxicity, reduce the dose by one third when changing opioid

Table 19: Morphine sulfate 10mg daily dose equivalents

Opioid and route of administration

Codeine: oral

Equivalent dose of 10mg of oral morphine sulfate

100mg

Opioid and route of administration

Dihydrocodeine: oral

Equivalent dose of 10mg of oral morphine sulfate

100mg

Opioid and route of administration

Oxycodone: oral

Equivalent dose of 10mg of oral morphine sulfate

6.6mg

Opioid and route of administration

Tramadol: oral

Equivalent dose of 10mg of oral morphine sulfate

100mg

Opioid and route of administration

Buprenorphine: transdermal patch

Equivalent dose of 10mg of oral morphine sulfate

4.16 micrograms/hour

Opioid and route of administration

Fentanyl: transdermal patch

Equivalent dose of 10mg of oral morphine sulfate

4.16 micrograms/hour

Individuals who require particular consideration include:

• history of substance abuse
• renal impairment
• recently discharged following surgery

• older and/or frail

Higher doses have a greater risk of serious harm (four times higher for 50-100mg MED, nine times higher for doses greater than 100mg MED). Such harms can include increased risk for falls and major trauma, and increased odds of road accident168^, [170] The risks of dependence are increased in individuals with current or history of problem substance use (including alcohol misuse) or mental health conditions (for example, major depression). Additional support and monitoring may be necessary when prescribing for individuals at risk of opioid misuse.157

Risks can be categorised by the timescale on which they may be seen, although some can occur in any timeframe.

Table 20: Common side effects of opioids

Short-term:

drowsiness, dizziness, confusion

constipation, nausea/vomiting

respiratory depression

Long-term:

dependence and addiction, even at therapeutic doses, following prolonged use (longer than three months)157

may adversely affect the immune system (immunosuppression) ^[171]

increased risk of myocardial infarction and cardiovascular revascularisation171

hyperalgesia – which is increased pain sensitivity^[172]

adrenal insufficiency

sexual dysfunction, fatigue and decreased levels of testosterone (in men and in women)[173]^,[174]

Additional factors to consider during any timeframe:

risk of overdose, fractures, abuse, dependence, diversion

interactions with other CNS depressant (such as anticonvulsants, benzodiazepines, gabapentinoids), with increased risk of respiratory depression and overdose ^[175]

Prescribers should consider the adverse effects against the limited long-term benefits, as there are few trials examining the efficacy of long-term opioid use (≥3 months) in those with chronic pain. There are limited numbers of studies of variable quality which demonstrate long-term efficacy.156^,171

Antidepressants

Benefits:

• Clinicians may consider a trial of duloxetine 60mg in people with chronic primary pain (including fibromyalgia, neuropathic pain and musculoskeletal) which is not adequately managed by analgesics, [176]^{, [177]} noting that:

• the licensed indication is diabetic neuropathic pain
• other guidelines consider it appropriate to try/consider unlicensed use in non-specific and neuropathic symptoms in lower back pain and fibromyalgia

Risks:

• Suicidality with increased risk of suicidal thoughts and acts, particularly in adolescents and young adults 18–21 years ^[178]

• Suicide and self-harm rates tend to be higher when antidepressants are started or stopped
• Individuals should be warned of this potential adverse effect during the early weeks of treatment and know how to seek help if required
• Switching antidepressants may be a marker of increased risk of suicidal behaviours in those aged 75 years and over when initiating antidepressant treatment¹⁷⁸

Anticonvulsants

Prior to commencement, it is good practice that agreement is established between the individual and prescriber that prescribing of gabapentinoids is a trial and that if treatment is ineffective (or no improvement in function), they will not be continued.

Benefits:

• Gabapentin and pregabalin have a specific place in therapy
• Carbamazepine should be considered for those with trigeminal neuralgia

Risks of medication related harm:

• Older adults, frailty, multimorbidity, polypharmacy, and renal impairment
• Gabapentin and pregabalin have been associated with a rare risk of severe respiratory depression [179]^{, [180]} even without concomitant opioid medicines

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

Total eradication of pain is unlikely, and evidence reviews frequently consider an intervention effective if it reduces pain by 30%154 to 50%.155

There is a high placebo effect, highlighting that biopsychosocial effects are contributory factors in pain management. For example, a Cochrane review showed pregabalin 300mg daily reduced pain intensity by 30% in 47% of patients, but the placebo was similarly effective in 42% of patients.¹⁵⁵

It is important to not only assess the impact of these medicines on pain levels, but also consider the effect on physical function, mental health and emotional factors (e.g. mood, anxiety, sleep, social and sexual function) that also contribute to effective pain management.

Evidence for effectiveness and risks

Opioids

There are few trials of efficacy of long-term opioid use (≥3 months) in individuals with chronic non-malignant pain, and limited numbers of studies with variable quality which demonstrate long-term efficacy.156^,171

Generally:

• Opioids should only be considered for short to medium-term treatment (less than three months) for carefully selected patients with chronic non-malignant pain, when other therapies have been insufficient, and the benefits are greater than the risks of serious harms such as addiction, overdose and death156^,159^,160
• Individual review is recommended within four weeks of starting opioid treatment or sooner if required.168 The frequency of review once the opioid regimen is established depends on the factors mentioned, but should be at least annually156 to identify possible harms and consider the effectiveness of treatment162^,163^,164^,165^,166^,167^,168
• Prescribers should consider the risks and harms against the benefits of taking opioids^{156,161,170,175}
• Higher doses have a greater risk of serious harm (four times higher for 50-100mg MED, nine times higher for doses greater than 100mg MED). Such harms can include increased risk for falls and major trauma, and increased odds of road accident168
• Due to tolerance developing, the analgesic effect of opioids lessens over time and individuals require higher doses to maintain the same level of pain relief153^,168^,185
• If a change from one opioid to another is required, the relative potency should be accounted for and dose equivalence charts used (see Table 19). Exercise caution when changing from one opioid to another, especially fentanyl due to its high potency (good practice point).

Morphine:

• Individuals should be considered as opioid non-responsive if 20mg of immediate-release morphine does not reduce pain intensity
• As there is no evidence of difference in pain control between opioids, morphine is the preferred cost-effective option154
• As more evidence is available, the accepted upper dosage limits are being reviewed and reduced. Current recommendations indicate the upper dosage levels should be less than 50mg to minimise longer term risks and adverse effects, and previous upper limits of 90mg to 120mg should be reviewed
• It is good practice to not prescribe more than 90mg/day MED175 without seeking advice from a prescriber specialising in pain[181]^,[182]
• It is good practice to use extreme caution when prescribing more than 120mg/day MED due to the risk of harm substantially increasing at these doses168
• Note palliative care and post-operative care are not included in chronic pain

Tramadol:

• Tramadol has high potential for drug interactions, due to opioid effect and an enhancement of serotonergic and adrenergic pathways
• It is good practice not to combine with other opioids for mild to moderate pain175
• One study considered tramadol as suitable for neuropathic pain, ^[183] however another found no significant difference between it and placebo160

Other opioids:

• Transdermal buprenorphine or fentanyl could be an option for treatment when there are reasons prohibiting oral administration.
• Fentanyl:
  • other analgesics and other opioids for non-malignant pain should be trialled before prescribing fentanyl patches
  • due to the potency of fentanyl the use of transdermal patches is contra-indicated in opioid-naive individuals
  • the use of immediate release fentanyl is not recommended as it is restricted for use for the management of breakthrough pain in adults using opioid therapy for chronic cancer pain, when other short-acting opioids are unsuitable
  • is suitable in renal impairment and use with caution^[184]
• Buprenorphine:
  • is an alternative for those with renal dysfunction (even severe) ^[185]
  • patches are available in several brands. They are available in different strengths and are not all interchangeable therefore buprenorphine patches should be prescribed by brand name
  • patches are not appropriate for individuals with acute pain and those who need rapid dose escalation
  • 7-day transdermal patches (5 to 20 micrograms) should be prescribed in line with SMC restriction: For use in elderly individuals (over 65 years) for the treatment of non-malignant pain of moderate intensity when an opioid is necessary for obtaining adequate analgesia
• Oxycodone:
  • requires dose adjustment in renal impairment
  • oxycodone and naloxone combination prolonged released tablets are not recommended by SMC
• Tapentadol use is restricted by SMC. See local formularies

Antidepressants

Medication which potentiates noradrenaline and serotonin noradrenergic mechanisms (serotonin norepinephrine reuptake inhibitors (SNRI) has some evidence in neuropathic pain. The evidence is not conclusive for or against the use of TCAs in chronic pain. Selective serotonin reuptake inhibitors (SSRI) have no high-quality evidence to support their use in the management of chronic pain.

Duloxetine

• A trial of duloxetine 60mg may be considered in people with chronic primary pain (including fibromyalgia, neuropathic pain and musculoskeletal) which is not adequately managed by analgesics,154^,176^,177^{, [186]} noting that

• the licensed indication is diabetic neuropathic pain
• other guidelines consider it appropriate to try/consider unlicensed use in non-specific and neuropathic symptoms in lower back pain and fibromyalgia

• To minimise the risk of side effects, especially nausea, it is good practice to start duloxetine at a lower dose of 30mg daily for two to four weeks before increasing to 60mg
• Review effectiveness and tolerability of duloxetine at four weeks and discontinue if there is no improvement in pain relief, physical function or subjective improvement. It is good practice to gradually reduce.

Tricyclic antidepressants (TCA)

• SIGN 2025 evidence review is not conclusive for or against the use of TCAs in chronic pain.176
• Other guidelines do consider the use of TCAs in chronic neuropathic pain, and clinicians should consider each person and their individual circumstances and chronic pain experience.183^,186
• Taking TCA at evening mealtime rather than bedtime might address the problem of people being unable to initiate sleep and reduce fatigue the following morning186
• Due to risk of side effects, especially sedation, it is good practice to start amitriptyline at a lower dose of 10mg daily and an alternative TCA could be considered to reduce side effects¹⁵⁶
• TCAs should be used with caution in the older adult or frailty due to anticholinergic effects and risk of falls2
• TCAs should not be used for the treatment of low back pain156^,186^,[187]

SSRIs

• There is no high-quality evidence to support the use of other antidepressants (such as fluoxetine, paroxetine and citalopram) in the management of chronic pain. Historically they have had a place in management, although unlicensed154
• There are potentially serious side effects of prescribing tramadol with an SSRI, such as serotonin syndrome

Table 21: Numbers needed to treat and harm for duloxetine

Medication

Duloxetine (50% pain intensity reduction with 60mg daily)

Indication

Chronic primary pain (including fibromyalgia, neuropathic pain and musculoskeletal) which is not adequately managed by analgesics

NNT176

7.1

NNT176

7

Good practice points:

When an antidepressant is used to manage chronic pain, the individual should understand that these medicines may help with quality of life, pain, sleep, psychological distress, even in the absence of a diagnosis of depression.

Concomitant depression:

Optimise antidepressant medication where possible in those with concomitant chronic pain and depression, rather than prescribe additional antidepressant medication.¹⁵⁶ Combinations (e.g. SSRI with mirtazapine or trazodone, or SSRI and TCA) should be considered carefully (see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027) to mitigate against the risk of adverse drug effects and should prompt consideration for specialist review.

Anticonvulsants

• Much of the trial data for the effectiveness of gabapentinoids is limited to 12-16 weeks duration155
• Gabapentinoids should not be used in low back pain, sciatica and spinal stenosis ^[188]
• Gabapentin or pregabalin could be considered for individuals with the specific conditions of post herpetic neuralgia or painful diabetic neuropathy155^{, [189]}
• Gabapentin or pregabalin could be considered for individuals with fibromyalgia, although this is unlicensed.189
• Good practice point: Evidence indicates maximal dose of pregabalin 600mg daily/gabapentin 3600 mg daily to achieve 30-50% pain intensity reduction),155^{, [190]} but if tolerated, minimum effective dose should be used
• Carbamazepine could be considered for trigeminal neuralgia, but individuals should be advised of adverse drug effects and interactions^,186^,[191]
• Review effectiveness of gabapentinoids or carbamazepine after four to six weeks of therapy and discontinue if ineffective
• Good practice point: there is limited place in therapy for other anticonvulsants and should not be started in non-specialist settings

• To minimise the risk of side effects with gabapentin and pregabalin, it is good practice to start at lower doses and titrate to lowest effective dose

Table 22: Numbers needed to treat and harm for gabapentinoids with 50% pain intensity reduction

Medication	Indication	NNT156	NNH175
Gabapentin doses up to 3600 mg daily190	Post herpetic neuralgia	8	8.6
Gabapentin doses up to 3600 mg daily190	Painful diabetic neuropathy	5.9	8.6
Gabapentin maximum 2400 mg daily	Fibromyalgia	5.4	8.6
Pregabalin 600mg daily	Post herpetic neuralgia	3.9155	11155
Pregabalin 600mg daily	Painful diabetic neuropathy	7.8155	11155
Pregabalin 600mg daily	Central neuropathic pain	9.8155	13.9155
Pregabalin 600mg daily	Fibromyalgia	11[192]	11
Carbamazepine	Trigeminal neuralgia (50% pain reduction)	1.7	2.1

When medicines should not be stopped?

These medicines can be stopped but should not be done abruptly. Reduction of therapy should be controlled, not sudden, to manage the risk of withdrawal symptoms.

Successful reduction requires shared decision-making and the individual’s participation in a person-centred review that considers the personal context. A person-centred assessment of risk versus benefit should occur before reducing or stopping medication to determine the effectiveness of treatment.

Safety - specific medication safety issues to highlight

Opioid use is receiving increasing attention, with opioid deaths in Scotland and the USA a major cause of public concern:

• Media coverage may raise specific concern about drugs which are in everyday use, such as fentanyl
• Individuals prescribed opioid medication should understand that many of these deaths are associated with unregulated products (with potentially very high doses of drug) and illicit drug use – and should understand their own situation in context
• National Records of Scotland shows that there were 1,172 deaths due to drug misuse in Scotland in 2023.^[193] Of these deaths, medication implicated included

• opiates/opioids (such as heroin/morphine and methadone): 937 deaths (80%)
• benzodiazepines (such as diazepam and bromazolam): 678 deaths (58%)

• gabapentin and/or pregabalin: 450 deaths (38%)

Generally:

• Potentially fatal interactions between medicines that cause CNS depression, particularly opioids, gabapentinoids and benzodiazepines

Opioids

• See table in benefits and risks

Antidepressants

• QTc prolongation
• Serotonin syndrome
• Increased anticholinergic burden, particularly TCAs
• Suicide risk (at initiation and cessation)
• Inhibition of cytochrome enzymes – pharmacokinetic interactions

Anticonvulsants

• Prescribers and individuals should be aware there is a significant risk of adverse effects with gabapentinoids, including drowsiness or somnolence, dizziness, nausea, weight changes (abnormal appetite), cognition and speech problems/ataxia,186^,188
• Individuals should be advised about the high incidence of adverse events leading to cessation of therapy in 18%-28% of patients155^,156^,186^,188
• Reduced renal function - requires dose reduction to reduce risk of toxicity and side effects
• eGFR is frequently used to quantify the degree of renal impairment and is readily available on laboratory results and clinical systems. However, the licences for gabapentin and pregabalin are based on creatinine clearance (CrCl) which usually relies on manual calculation. These are shown in Tables 23 and 24 below.
• Clinical calculators are available to support calculation

Table 23: Gabapentin

CrCl ml/min b	Max recommended dose (BNF)	Additional Info
50-79	600-1800mg daily in three divided doses	-
30-49	300-900mg daily in three divided doses	-
15-29	150-600mg daily in three divided doses	150mg dose to be given as 300mg in three divided doses on alternate days
<15	150-300mg daily in three divided doses	150mg dose to be given as 300mg in three divided doses on alternate days

^b doses based on Creatinine Clearance (CrCl) and not eGFR

Table 24: Pregabalin

CrCl ml/min b	Max recommended dose (BNF)
30-60	Initially 75mg daily and maximum 300mg daily in two to three divided doses
15-30	Initially 25-50mg daily and maximum 150mg daily in one to two divided doses
<15	Initially 25mg once daily and maximum 75mg once daily

^b doses based on Creatinine Clearance (CrCl) and not eGFR

• Respiratory depression

Risk of severe respiratory depression noted with both gabapentin and pregabalin.179^,180

Individuals at higher risk who may require adjustments in dose or dosing regimen include:

• compromised respiratory function, respiratory or neurological disease
• renal impairment
• those using concomitant central nervous system (CNS) depressants e.g. opioids, benzodiazepines
• people older than 65 years

• Risk of foetal abnormalities

• MHRA noted findings from a study that showed that pregabalin, like some other antiseizure drugs, is associated with a slight increased risk of major congenital malformations if used in the first trimester^[194]
• Advice for health professionals can be found in the MHRA Pregabalin Drug Safety Update
• More research is required to define the pregnancy safety profile of gabapentin. Pregnant women and women of childbearing potential should be made aware of the lack of data for most pregnancy outcomes. Gabapentin should only be used during pregnancy where benefits of treatment are considered to outweigh any potential risks^[195]

How and when to reduce and stop medication – deprescribing

Discuss withdrawing medication if:

• the condition for which the medicine was prescribed has resolved
• it is no longer benefiting the patient
• problems associated with dependence have developed
• the adverse effects of the medicine outweigh the benefits
• there are drug interactions, e.g. where other central nervous system depressants are being used or prescribed (e.g. alcohol, opioids)
• the individual wants to stop taking the medicine
• with gabapentinoids, if the individual is planning or becomes pregnant

General:

• Any reduction should be gradual, according to the individual’s needs, unless urgent safety issue
• Individuals should be supported through the dose tapering process, maintaining regular contact with the healthcare team involved in their treatment, to allow for ongoing assessment of withdrawal symptoms, pain control and impact on function and quality of life
• Tapering can be paused if an individual is experiencing difficulty and can be revised and continued with a more gradual reduction
• There should also be planning for short-term pain flares and for any withdrawal effects for example

• opioids - agitation, muscle aches, restlessness, anxiety
• gabapentinoids - agitation, anxiety, insomnia, or flu-like symptoms, confusion, headache, lethargy and a return of nerve pain

• Discuss withdrawal symptoms
• explain that withdrawal can be difficult and may take several months or more
• although withdrawal symptoms do not affect everyone, it is not possible to predict who will be affected
• withdrawal symptoms vary widely in type and severity, can affect both physical and mental health, may occur at any time during withdrawal or be delayed in onset and can change over time or persist over a prolonged period

Opioids

• Abrupt discontinuation should be avoided to prevent severe withdrawal symptoms
• The Clinical Opiate Withdrawal Scale (COWS) can be used in all settings to monitor opioid withdrawal
• Tools are available to form the basis for discussing the detail of a planned reduction/cessation, so that informed joint decisions can be made around the treatment plan (e.g. Pain Management Taper Calculator)
• Options for reduction include:
• use of a single modified release opioid, and when the dose is stable, reduce
• keep the modified-release dose stable and then wean down immediate-release as needed to the point of stability, then the modified-release dose can be reduced by 5%-10% per dose per week170
• if taking immediate release preparation, change to or add a modified-release preparation, and then withdraw the immediate-release opioid186
• Due to the small number of studies (with varying heterogeneity) any specific opioid analgesic deprescribing strategy cannot currently be recommended^[196]

Antidepressants

• Antidepressant reduction should be gradual, over a period of no less than two weeks. Guidance for reducing, stopping and switching specific antidepressant medicines can be found in the Maudsley Prescribing Guidelines¹⁷⁸
• All antidepressants have the potential to cause withdrawal phenomena when taken continuously for six weeks or longer
• Antidepressants should not be stopped abruptly unless a serious adverse event has occurred (e.g. cardiac arrhythmia with a TCA)
• Discontinuation symptoms may occur, especially in drugs with a short half-life even if the individual misses a dose e.g. an antidepressant with potent anticholinergic adverse effects may be associated with diarrhoea on discontinuation

Gabapentinoids

• Slowly reducing the dose will minimise symptoms of withdrawal when reducing gabapentinoids
• Suggested reduction regime for analgesic use would be:
• Gabapentin: reduce at maximum daily rate of 300mg every week
• Pregabalin: reduce at maximum daily rate of 50-100mg every week

• Faster reduction may be considered (e.g. every two to three days) depending on patient response

Supporting people who do not or cannot reduce/stop

These are not classed as essential medicines but should not be stopped abruptly. Individuals who cannot stop their medication should be encouraged to reduce to the lowest effective dose.

Individuals should be regularly encouraged to self-manage and use non-pharmacological treatments of chronic pain where appropriate. Avenues for reducing or stopping medication should remain available to the individual.

Good practice point: Clinicians should consider prescribing naloxone for those prescribed an opioid and who may be at risk of an opioid overdose.[197]^,[198]

Take-Home Naloxone Programme is available across all boards in Scotland.

Specific areas/situations where medication may need to be introduced or increased

If the presenting pain condition changes or symptoms worsen, undertake a further pain assessment, considering potential cause of flare-up and consider appropriate management (which may include rest, heat packs, pacing, use of short-term non-steroidal), dependent on the cause for the presenting pain.

Antidepressants

If treatment is reviewed and the patient has noticed an improvement in their quality of life, pain, sleep or psychological distress since the antidepressant was initiated, then a joint decision with the individual should be made whether a further increase is needed. Always ensure ongoing review is in place to determine the benefits of any changes made.

Before starting or continuing treatment with an antidepressant, ensure that all suitable management options, including non-pharmacological approaches and watchful waiting, have been discussed with and offered to the person. Explain and discuss the risk of dependence and the factors that may increase this risk.

Consider delaying prescribing if the person needs more time to think about their options or the prescriber needs to consult with other members of the healthcare team. If prescribing is delayed, ensure that a follow-up appointment and timeframe is agreed and arranged.

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• Ask individuals whether they would like to have support during appointments from a family member, carer, advocate or other person close to them.
• Discuss with the person the benefits and risks of continuing the current dose, adjusting the dose or stopping the medicine. Base decisions on these discussions and ensure ongoing regular reviews are in place.
• Provide written materials to support discussions and decisions, or before the review/consultation to inform and support informed decision-making.
• Consider whether the individual needs support with taking their medicines, such as a medication chart or adherence aid, or if they need further information.

Is drug therapy tailored to the individual?

• Ensure the individual is provided with a plan for withdrawal that is tailored to their situation, and the medicine they are taking, and that they are aware of how the withdrawal will be carried out

⦁ Ensure they understand that if side effects are a problem, solutions such as adjusting dosages, timings or switching to an alternative can be considered.

Agree the plan

• Continuity of care is important to foster collaborative, trusting and supportive relationships with people, considering medication at all stages of prescribing. Shared decision-making allows people to actively participate in their care.
• Supported self-management encourages, supports and empowers people to manage their long-term conditions and live well with their conditions
• Consider providing details of peer support services including national and local support groups for people who are withdrawing from a medicine

• Have clear expectations of future benefit assessment, potential harms from medication and reasons to stop

Decision support tools

• self-management/support tools

• decision aids for healthcare professionals

Patient resources:

NHS Inform: Patient information on chronic pain

Includes: General overview, Self-help activities - What can I do for myself?, link to chronic pain self help guide and links to other organisations.

Flippin’ Pain™ website

A public health campaign with a clear goal: to change the way we think about, talk about and treat persistent pain. Includes information on chronic pain, real life stories and resources to help understand pain and move towards recovery.

Brainman^TM Understanding Pain in less than five minutes

5-minute video explaining chronic pain and options to support recovery

Pain Association Scotland website

A national charity that delivers professionally led self-management pain education in the community with local groups, pain management courses and assorted videos.

Tel: 0800 783 6059 (to join a group)

Versus Arthritis website (merger of Arthritis Care and Arthritis Research UK)

Information on: arthritis and musculoskeletal conditions, how to manage symptoms including pain, sleep, fatigue and local groups.

Tel: 0800 5200 520

Live Well with Pain website - Created by a small group of healthcare professionals working in pain management, using a self-management approach with their patients. Also includes input from people who themselves live with persistent pain. Includes: Ten Footsteps programme and self-management resources.

Pain jigsaw Interactive version of pain jigsaw from NHS Fife

Patient led videos on chronic pain produced by NHS Greater Glasgow and Clyde pain team. Covers understanding of chronic pain, activity, flare ups, sleep, and stress.

Increased pain and tolerance with morphine-like medicines video from NHS Ayrshire and Arran

Not just painkillers – Your pain and how you can help it booklet from NHS Lothian with information on pain in general, opioid analgesics and self-help advice

Reducing and stopping opioids – information for patients leaflet from Oxford University Hospitals including information on side effects of opioids, why stop, help during reduction

Pain data website – medication information leaflets for patients includes leaflets on co-codamol, tramadol, dihydrocodeine and others.

Pain Concern Helpline 0300 123 0789

Resources for healthcare professionals:

Live Well with Pain website Wide range of leaflets and information sheets to download and print, including self-management information leaflets and tools, medicines information for people with pain and information posters for public waiting areas.

GP pain assessments

Live Well with Pain Health Check tool/questionnaire

The Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) pain score assessment tool

British Pain Society Pain Scales Single page pain assessment. Suitable for ongoing use to evaluate effectiveness of therapies.

Opioid information

Pain Management opioid reduction calculator

Select opioid, starting dose, target (complete reduction or switch to another), weekly percentage reduction and website calculates weekly doses.

Increased pain and tolerance with morphine-like medicines video from NHS Ayrshire and Arran.

DIRE score for opioids Assesses candidacy for long-term opioid analgesia based on seven multiple choice questions.

GP Practice prescribing management and review systems

Pain management consultation model for primary care

Suggested content for 3 consultations:

1. build trust, exclude differentials

2. pain management plan

3. promote self-management

Primary care chronic pain management MDT Includes: primary care MDT management pathway and exemplars letters for chronic pain medication reviews.

National Therapeutic Indicators (NTIs) Practice specific prescribing data

Deprescribing practice lessons learned Top 10 tips and action plans from GP practices.

Education

NES Chronic Pain Knowledge Hub on TURAS Free but requires NES TURAS account

Webinar: Chronic pain: why it can only be in the brain (free) (discussion of a radical new perspective on the neurobiology of chronic pain and how this can revolutionise practice.)

NES webinar on challenging consultations and recorded consultation of patient with fibromyalgia with drug seeking behaviour. Free but requires NES TURAS account.

Webinar: Dealing with drug seeking behaviour Presentation with practical hints and tips on how to recognise and manage drug seeking behaviour.

National therapeutic indicators for this hot topic

National therapeutic indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Opioid and gabapentinoid dependency: High dose opioids (morphine daily equivalent 50mg or more) see Chart 2
• Analgesics: opioids (excluding tramadol) defined daily doses per list size
• Opioid and gabapentinoid dependency - High dose opioids (morphine daily equivalent 90mg or more)
• People receiving three or more of benzodiazepine/z-drug, opioid (including tramadol), gabapentinoid, antidepressant or antipsychotic (excluding depots)

8.1.2 Hot Topic: Type 2 Diabetes Mellitus - the management of glycaemic control

What is the aim of this hot topic and therapy?

Management of type 2 diabetes mellitus (T2DM) can reduce symptoms of hyperglycaemia and reduce long-term complications. The aim of this hot topic is to ensure that these are prescribed safely.

Is this an essential medicine?

Should be considered essential, for treatment of symptomatic hyperglycaemia.

Important benefits and risks of treatment, including any groups where specific considerations are required

People with T2DM can achieve remission by diet control, weight management and lifestyle changes, but frequently people require pharmacological treatment. Reduction in hyperglycaemia, to prevent the long-term complications is important,^[199] but equal emphasis is placed on reducing cardiovascular and renal risk, independent of glycaemic control. [200]

Glycaemic control is a balance between minimising complications of hyperglycaemia and the risk of hypoglycaemia (with particular risk of falls and hospitalisation, in those who are frail). Figure 7 shows characteristics and considerations that individuals and clinicians can consider together to assess “what matters to me” when determining individual glycaemic control.

Some individuals with diabetes and health inequalities will require additional support to manage their long-term conditions due to an increased risk of poorer medication adherence and complications associated with diabetes.

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

Lifestyle management is the fundamental aspect of diabetes care.

Weight loss can delay the onset of type 2 diabetes^[202] and can also lead to remission. [203]

First line pharmacological treatment is metformin, ^[204] due to:

• reduction in cardiovascular events and death
• beneficial effects on HbA1c
• being weight neutral
• reduced risk of hypoglycaemia

unless:

• intolerance due to gastrointestinal side effects, which can be minimised by gradual dose increase and by modified release preparations
• reduced renal function (reduce dose if eGFR<45ml/min, or stop if less than 30ml/min)
• lactic acidosis

Managing cardiovascular risk:

• Primary and secondary prevention of cardiovascular disease (CVD) should be addressed, e.g. statins, antihypertensives, smoking, obesity.
• Newer classes of blood glucose lowering agents, in addition to improved glycaemic control, have positive outcomes for those with, or at risk of, major adverse cardiovascular events (MACE), hospitalisation for heart failure (hHF), cardiovascular death and chronic kidney disease (CKD) progression.

If the individual with T2DM has:

• existing atherosclerotic cardiovascular disease (ASCVD), chronic heart failure:
• sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 agonists (GLP-1RA), should be recommended, independent of glycaemic control.

• consider use of SGLT-2i and GLP-1RA^[205] if there are cardiovascular risk factors:
  • Adults over 40 years: QRISK2 more than 10%
  • Adults under 40 years: a clinically assessed elevated lifetime risk of cardiovascular disease (defined as the presence of one or more cardiovascular risk factors):
    • hypertension
    • dyslipidaemia
    • smoking
    • obesity
    • family history (in a first-degree relative) of premature cardiovascular disease (males less than 45 years, females less than 55 years)
• chronic kidney disease (eGFR < 60 ml/min/1.73m²)
  • check albumin to creatinine ratio (ACR) to determine appropriate medication (see Table 25)

Table 25: Treatment options in CKD

Treatment options	ACR <3mg/mmol	ACR 3-30mg/mmol	ACR >30mg/mmol
ACEi/ ARB to highest tolerated dose	No	Yes N.B. lower threshold than if no diabetes present	Yes
SGLT-2i (dependent on licence) in addition to ACEi/ARB	No	Consider	Offer

Prescribing choices

These are preventative interventions with outcomes realised over 10 or more years. See Appendix A1 for individual NNTs. Consider risks of side effects which may outweigh the benefits of therapy.

SGLT-2i contra-indications/cautions (not exhaustive):

• people 75 years and older are at increased risk of volume depletion
• not recommended for initiation when eGFR <15 ml/min/1.73m²
• have less glucose-lowering efficacy when eGFR <45 ml/min/1.73m²
• should be avoided in those with factors predisposing to diabetic ketoacidosis (DKA)/euglycaemic diabetic ketoacidosis (eDKA) ^[206]
  • pancreatic insufficiency
  • drug or alcohol abuse disorder
  • a low/ultra-low carbohydrate or keto diet
  • excessive alcohol consumption
• frequent bacterial urinary tract infections or genitourinary yeast infections
• low bone density or high risk for falls/fractures
• foot ulceration

When medicines should not be stopped

Continue diabetic medication when:

• symptomatic hyperglycaemia needs to be treated. Alternative treatments may need to be considered
• additional benefits (of SGLT-2i or GLP-1RA) are present

Safety – specific medication safety issues to highlight

Reduced renal function:

• metformin
• SGLT-2is
• GLP-1RAs
• Dipeptidyl peptidase 4 inhibitors (DPP-4i)
• in addition to ACEi, ARBs, diuretics and NSAIDs

Frailty:^[207]

• Increasing frailty increases the risk of hypoglycaemia (and therefore falls and hospitalisation)
• Consider less stringent targets (see individualised targets below)

Other:

• Dual prescribing of DPP-4i and GLP-1RA – stop DPP-4i, as no benefit from dual prescribing
• Less effective antidiabetic medication, e.g. pioglitazone, DPP-4i, sulfonylureas (unless for symptomatic control of hyperglycaemia). Note that sometimes HbA1c may be within target range, but these agents may not be contributing to HbA1c target reduction
• Medication Sick Day Guidance

How and when to reduce and stop medication – deprescribing

Stop: if an antidiabetic medication is no longer indicated or safe. There is no need to down titrate.

Immediate dose reduction: when renal impairment requires a dose reduction or altered HbA1c target.

Always reinforce lifestyle modifications.

Specific areas/situations where medication may need to be introduced or increased

1. If target HbA1c is not achieved

2. If comorbidities, such as ASCVD, HF, CKD, even if HbA1c within target range

Action: Consider additional therapies in line with medication effectiveness section

Person-centredness: supporting collaborative decision-making and understanding

Key points to discuss with the individual:

Does the person understand the outcomes of the review, including risk and benefits?

• Increase in therapy may be to improve glycaemic control, have positive long-term outcomes in ASCVD/HF/CKD, or both

• Treatment may be reduced due to risk of adverse effects, renal impairment or individualised treatment, especially if frail.

Is drug therapy tailored to the individual?

• Consider frailty

• What is the impact of comorbidities such as poor mental health?

Agree the plan

• Non-pharmacological and lifestyle management is a fundamental aspect of diabetes care and includes: diabetes self-management education and support; nutritional advice; physical activity; smoking cessation counselling; psychosocial care

Decision support tools

- self management/support tools

- decision aids for healthcare professionals

• My Diabetes My Way website
• Diabetes UK website
• NHS inform website – type 2 diabetes

National Therapeutic Indicators for this hot topic

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Individuals with T2DM prescribed a SGLT-2i/GLP-1RA and existing therapy suggestive of atherosclerotic cardiovascular disease (ASCVD) see Chart 3
• Antidiabetic drugs (metformin %) - Number of people prescribed metformin: this should have a high percentage
• Antidiabetic drugs (polypharmacy %) - Number of people prescribed three or more categories of diabetes medication
• Falls, fractures, delirium (sulfonylureas %) - Number of people aged 75 years and over prescribed sulfonylureas

8.1.3 Hot Topic: Management of constipation in adults

Treatment: Laxatives (bulk forming, osmotic, stimulant)

What is the aim of this hot topic and therapy?

Constipation is typically defined as bowel motions less than three times a week. ^[208] In practice constipation is often defined as passage of stools less frequently than the person's normal pattern. Constipation is a common symptom and can be short-term or chronic, if lasting three months or more. Laxatives are commonly prescribed, and this hot topic is to ensure they are prescribed appropriately.

Is this an essential medicine?

There are some patient groups where symptoms may persist despite lifestyle and medication changes, for example when constipation inducing drugs cannot be stopped or in chronic conditions, e.g. Parkinson’s disease, multiple sclerosis.208

Laxatives are indicated in relief of faecal impaction, overflow diarrhoea, and where a bowel motion is unlikely to occur without intervention.

Excluded from this hot topic:

• people receiving palliative care
• bowel preparation prior to investigation or surgery
• the management of chronic laxative misuse
• the management of organic causes of secondary constipation

Important benefits and risks of treatment, including any groups where specific considerations are required

The healthcare professional (HCP) should take a history to assess for potential underlying conditions and consider referral to secondary care where appropriate e.g. pelvic floor dyssynergia, suspected colorectal cancer (urgent referral required).208

Before starting a laxative, consider other factors which may be contributing to the symptoms (e.g. inadequate fluid intake, lack of physical activity, failure to act on urge).208 Non-pharmacological interventions should be tried first.

Non–pharmacological interventions (see decision support tools)

First line evidence based dietary advice for constipation should include:

• increasing fibre in the diet
• increasing physical activity
• ensuring adequate fluid intake (1.5-2 litres daily, unless fluid restricted)
• going to the toilet when needing to (“call to stool”)
• good positioning

Medication induced constipation

Many medicines are implicated in inducing constipation, including those with high anticholinergic burden.^[209] Such medication should be reviewed and stopped or reduced where appropriate.208

Table 26 Medication that can cause constipation208

Medication class

Analgesics

Examples

opioids (occurs in up to 80% of patients, even with concomitant use of laxatives)

nonsteroidal anti-inflammatory drugs (NSAID)^[210]

Medication class

Antidepressants

Examples

tricyclic antidepressants

Medication class

Antipsychotics

Examples

amisulpride, clozapine, or quetiapine

N.B. constipation can be life threatening in those prescribed clozapine

Medication class

Antiseizure drugs

Examples

carbamazepine, gabapentin, oxcarbazepine, pregabalin, or phenytoin

Medication class

Calcium-channel blockers

Examples

verapamil

Medication class

Diuretics

Examples

can lead to dehydration which can cause or exacerbate constipation

Medication class

Anticholinergics

Examples

antihistamines, e.g. hydroxyzine

antispasmodics, e.g. hyoscine or dicycloverine

antimuscarinics, e.g. procyclidine and oxybutynin

Medication class

Some antacids/mineral supplements

Examples

aluminium-containing antacids; iron or calcium supplements (take reducing dose into account)

Do not prescribe laxatives if there is suspected:208

• intestinal obstruction or perforation
• paralytic ileus
• Crohn's disease or ulcerative colitis
• toxic megacolon

Avoid certain laxatives in specific circumstances:

• colonic atony or faecal impaction (bulk-forming laxatives)
• severe dehydration (bisacodyl)
• galactosaemia (lactulose)
• history of hypersensitivity to peanuts (arachis oil enema)

Prescribe laxatives with caution if there is:²⁰⁸

• a risk of misuse (e.g. in eating disorders) – due to this, there is a limit to the number of stimulant laxative medications that can be bought over the counter
• a risk of electrolyte imbalance, such as hypokalaemia, which can occur with long-term use
• caution with macrogols in
• cardiovascular disease due to risks of fluid and electrolyte disturbance
• ischaemic colitis
• low salt diet – many preparations are considered high in sodium, therefore check individual summary of product characteristics (SPC)
• caution with lactulose in lactose intolerance - may cause diarrhoea
• caution with prucalopride in ischaemic heart disease or arrhythmias
• pregnancy – keep under review to avoid use becoming long-term

• bulk forming laxatives should not be prescribed for patients with opioid induced constipation; suspected faecal impaction nor taken at bedtime

Adverse effects

• laxatives may cause diarrhoea
• other side effects include crampy pain, bloating, flatulence, nausea and vomiting ^[211]
• macrogols can counteract the effect of starch-based food thickeners by liquifying the starch and therefore eliminating the thickening effect ^[212]
• prescribers should be aware PEG laxative such as PEG 4000, PEG 3350 (e.g. Laxido®) may reduce plasma sodium levels²¹¹

• long-term use and misuse of laxatives is associated with electrolyte imbalance, such as hypokalaemia

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

Faecal impaction treatment:

• osmotic laxatives are the first-line treatment, especially if there are hard stools
• an oral stimulant laxative should be prescribed for those with soft stools, or with hard stools after a few days’ treatment with a macrogol. This can be started or added to the macrogol treatment
• If the individual has not fully responded, then
  • in those with soft stools, rectal laxative administration should be considered e.g. bisacodyl suppository
  • harder stools may require glycerol, or glycerol and bisacodyl, with docusate sodium or sodium citrate enema as alternatives²¹²
• bulk-forming laxatives, e.g. ispaghula are contra-indicated

Constipation208

If non-pharmacological options fail, then a stepped treatment approach should be undertaken:

• first line: bulk forming laxatives e.g. ispaghula. Note: individuals prescribed bulk forming laxatives should maintain adequate fluid intake during treatment
• second line or add on: osmotic/stool softening e.g. lactulose, macrogol
• third line: add in stimulant e.g. senna, sodium picosulfate

NICE recommend alternative drugs such as prucalopride for constipation which has not responded to above treatment.²⁰⁸ However this is not currently recommended by Scottish Medicines Consortium and should not be routinely prescribed.

HCPs should be aware that some individuals may purchase over the counter remedies which increase bowel movement frequency and cause side effects such as flatulence. Psyllium has a bulk forming effect and should not be taken by those prescribed opioids or suspected faecal impaction or at bedtime.²¹¹

If symptoms do not improve with above treatments, then consider

• biochemical factors e.g. hypothyroidism, hypercalcaemia²⁰⁸
• specialist advice should be sought²⁰⁸
• referral to continence service or dietician services²⁰⁸

When medicines should not be stopped

• faecal impaction regimes should be fully completed
• when symptoms persist after review of lifestyle and medication changes
• when constipation-inducing medication cannot not be stopped
• when constipation is an intrinsic part of another condition e.g. Parkinson’s disease, multiple sclerosis

Safety – specific medication safety issues to highlight

Long-term use and abuse of laxatives is associated with fluid loss and electrolyte imbalance, such as hypokalaemia. Individuals should stop treatment if they experience symptoms of fluid and electrolyte disturbances e.g. thirst, lethargy.²⁰⁸

Consider if the individual is buying over the counter laxatives before prescribing and if any potential abuse.

Patients with impaired cardiovascular function: For the treatment of faecal impaction the dose should be divided so that no more than two sachets are taken in any one hour.

How and when to reduce and stop medication – deprescribing

People prescribed multiple laxatives should be reviewed. Education is key in helping individuals understand why multiple laxatives are not recommended long-term along with the importance of making healthier choices e.g. diet and physical activity.

NICE recommend:

• reducing/stopping stimulant laxatives first then reviewing response
• reducing/stopping other laxatives gradually where appropriate in individuals prescribed multiple laxatives
• laxatives should not be abruptly stopped in individuals prescribed more than one laxative²⁰⁸

Caution should be taken stopping/reducing antimuscarinic drugs which are deemed to be contributing towards constipation. Such drugs should be reduced gradually to prevent withdrawal symptoms e.g. diarrhoea, sweating, vomiting.^[213]

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• Help the individual to understand what a “normal” bowel habit is for them. Educate people on the potential risks of long-term laxative use e.g. electrolyte imbalance

Is drug therapy tailored to the individual?

• Individuals prescribed laxatives for overflow diarrhoea may struggle to understand the rationale behind laxative treatment. They may incorrectly stop before disimpaction treatment is complete, due to initial worsening of diarrhoea.
• Check that the individual understands the reason for reducing/stopping constipation inducing drugs.
• Consider those with reduced mobility and access to toilet facilities.²⁰⁸

Agree and share the plan

• Educate on non-pharmacological methods for managing constipation
• Ensure any “red flag” symptoms are recognised and addressed e.g. unintended weight loss, bleeding, iron deficiency anaemia

Decision support tools

• self-management/support tools
• decision aids

NHS Inform – summary of constipation, causes, treatment and prevention

Fibre food fact sheet from the Association of UK Dietitians

5-a-day fruit and vegetable fact sheet from the Association of UK Dietitians

8.1.4 Hot Topic: Parkinson’s disease

What is the aim of this hot topic and therapy?

Is this an essential medicine?

Antiparkinsonian medicines are essential medicines for treating the motor complications of Parkinson’s disease (PD). For most people with PD, medication is the only way to control their symptoms. The correct medication must be given on time and should not be stopped suddenly as this may result in severe complications such as: ^[214]

• Unable to swallow (increasing the risk of aspiration)
• Unable to speak and/or move (increasing their dependence on others)
• Acute akinesia (feeling frozen and stiff and being unable to move one’s muscles)
• Neuroleptic malignant syndrome (a life-threatening complication characterised by hypothermia)

Care must be taken when absorption may be impaired, for example in gastroenteritis or surgery and in people who become nil by mouth.

During admission to hospital, care homes or during other transitions of care, poor management of antiparkinsonian medications can lead to poor outcomes for individuals. These may continue following discharge. Everyone administering antiparkinsonian medication should be aware of the importance of dosage timing.^[215]

Important benefits and risks of treatment, including any groups where specific considerations are required

Most people with PD will be managed by a specialist in movement disorders and/or a multidisciplinary team, including a Parkinson's disease nurse specialist, physiotherapist and occupational therapist, who can advise on the management of both motor and non-motor symptoms and complications, to support improvements in activities of daily living.

Management should be individualised based on the person's symptoms and wishes, comorbidities, other medications and potential benefits and harms of the different drug classes. It should be aimed at reducing movement dysfunction, tremor and postural instability, while managing cognitive changes and minimising side effects.

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

For early, symptomatic PD, the first-choice options include: ^[216]

• levodopa
• a non-ergot dopamine agonist such as pramipexole, ropinirole or rotigotine patch
• a monoamine oxidase type B (MAO-B) inhibitor such as selegiline

The choice of therapy depends on multiple factors such as individual preference and the expected risks and benefits of the medications in that individual. Medication should be initiated and followed up by a specialist.

If the individual has developed dyskinesia (involuntary movements) and/or motor fluctuations, including medicines 'wearing off', consult a PD specialist to consider modifying the individual’s therapy.216 Adjuvant treatment available includes catechol-O-methyl transferase (COMT) inhibitors (such as entacapone or opicapone) and amantadine.

Liaise with the PD specialist if changes to antiparkinsonian medication are needed.

• Only start or alter antiparkinsonian medication on the advice of the PD specialist
• Titrate drug treatment according to recommendations made by the PD specialist
• Do not suddenly stop any antiparkinsonian medication, as this can precipitate acute akinesia or neuroleptic malignant syndrome
• Specify times of medication administration
• Ensure that changes to repeat medications are made accurately and promptly

Factors that aid or impair adherence in this area and how to address them

• Co-careldopa and co-beneldopa are available in various strengths and formulations which facilitate adaptation of regimes to enable optimal control. For example, dispersible co-beneldopa may be a useful product where swallow is difficult in the morning or rapid onset of action is required.^[217]
• Caution should be exercised in the use of a liquid formulation where swallowing thin liquids is provoking cough, and recommendations have been made to avoid thin fluids. In this situation, a crushed tablet given in yoghurt may be a safer and more effective way to administer. Note, crushing tablets may change their licensing status to “off-label”.
• Transdermal formulations may be a useful option if there are swallowing difficulties present. However, specialist input is required to advise on suitable doses to use; refer to local guidance.

When medicines should not be stopped

These medicines must not be stopped suddenly as this may lead to acute akinesia or neuroleptic malignant syndrome. Care must be taken when absorption may be impaired, for example in gastroenteritis or surgery and in people who become nil by mouth.

Safety – specific medication safety issues to highlight

A key issue with antiparkinsonian medication is timing:^[218]

• Medication should be taken at specific times to ensure that the control of symptoms is maintained without deterioration. Delay of medication can result in someone being unable to function independently at work or at home, and becoming reliant on others for simple everyday activities such as walking and eating
• It is crucial not to stop, omit or delay PD medications for any significant length of time (more than 30 minutes)214 as this may cause significant exacerbation of symptoms and distress
• In extreme cases, missed doses may lead to the potentially fatal neuroleptic-like malignant syndrome (NMS)

If the individual cannot remember to take their medication on time, consider exploring adherence issues and strategies to help remember medication. These could include aids such as pill timers, apps, alarms and dosette boxes.

Individuals may receive support from carers around medication. Everyone involved in the care of someone with PD should be aware of the importance of the timing of medications and strategies should be in place supporting this.

If a person with PD is admitted to hospital, a care home, or respite care, ensure that staff are aware of the risks of sudden changes in antiparkinsonian medication and the importance of adhering to prescribed dosage and timing of medications.

People with PD who are admitted to hospital or care homes should have their medicines:

• given at the appropriate times, which in some cases may mean allowing self-medication
• adjusted by, or adjusted only after discussion with, a specialist in the management of Parkinson's disease

Parkinson’s UK have a range of tools, resources and learning to support healthcare professionals to deliver time critical medication to people with Parkinson's as part of their Get It On Time campaign.

If the individual is unable to swallow the medication, consider suggestions such as medication review (of other non-antiparkinsonian medication), different-shaped tablets/capsules and soluble formulations. Ensure input from Speech and Language Therapy (SALT) to complete a full swallowing assessment and recommend strategies.

Explore any other difficulties in taking their current medication. Consider dexterity issues and the ability to open packaging, exploring alternatives where appropriate.

Impulse control disorders

Impulse control disorders (compulsive gambling, hypersexuality, binge eating or obsessive shopping) can develop in a person with PD who is on any dopaminergic therapy at any stage in the disease course. This applies particularly to those with a history of impulsive behaviours, alcohol consumption or smoking. Individuals should be informed about the different types of impulse control disorders. Although particularly noted with the dopamine agonist class of medications, this side effect can occur with any dopaminergic therapy.

It is essential that the specialist PD team are informed if these symptoms are detected, so they can advise on medication alteration for the individual.

Medicines to avoid

Some medications are contra-indicated in individuals with PD, care should be taken to review individual drug information when prescribing new medications.

Contra-indicated medications include (not exhaustive):

• haloperidol
• metoclopramide
• prochlorperazine
• chlorpromazine
• fluphenazine
• perphenazine
• trifluoperazine
• flupentixol

How and when to reduce and stop medication – deprescribing

Do not suddenly stop any antiparkinsonian medication, as this can precipitate acute akinesia or neuroleptic malignant syndrome.

Specific areas/situations where medication may need to be introduced or increased

Individuals with Parkinson’s disease often suffer from non-motor symptoms. These can include:^[219]

• constipation, nausea and vomiting
• pain
• sleep disturbance and daytime sleepiness
• depression and anxiety
• dementia and cognitive impairment
• impulse control disorders and psychotic symptoms
• orthostatic hypotension
• speech and swallowing problems and weight loss
• excessive salivation and sweating
• bladder and sexual problems

Individuals should be asked about non-motor symptoms which might be impacting on their quality of life. Parkinson’s UK’s website has information on these symptoms. There is a downloadable non-motor symptoms questionnaire completed by the person and/or their family/carers, which may help assess symptoms.

Most people with PD will be managed by a specialist in movement disorders and/or a multidisciplinary team, including a PD nurse specialist, who can advise on the management of non-motor symptoms and complications. However, primary healthcare professionals may have a role to play in the management of some of these issues, depending on local guidelines and expertise.

Constipation:

• Consider a stepped approach to the management of constipation in PD
• Refer to Parkinson's UK booklet Looking after your bladder and bowels when you have Parkinson's
• See constipation hot topic for more information and treatment options
• If constipation persists, liaise with the PD specialist team, as alteration of antiparkinsonian medication may be helpful

Nausea and Vomiting:

Mild nausea or vomiting can be associated with starting or increasing the dose of levodopa or a dopamine agonist:

• Initially, if nausea or vomiting is mild and related to starting or increasing the dose of levodopa or a dopamine agonist:
  • Reassure the individual that nausea often settles over time as tolerance to adverse effects builds up
  • Advise to take their medication with food
• If nausea or vomiting persists, is severe, or is unrelated to levodopa or dopamine agonist drug treatment, seek specialist advice:
  • Do not use metoclopramide or prochlorperazine anti-emetics — these can cause or exacerbate parkinsonism

Pain:

• Offer management for the following types of pain in primary care:
  • Musculoskeletal pain
  • Radicular neuropathic pain (shooting pain)
  • The Parkinson's UK information sheet Pain in Parkinson's covers the management of multiple common types of pain in PD
• Seek specialist advice or arrange a specialist review if pain remains uncontrolled
• Liaise with, or arrange a review with, the PD specialist team for the following types of pain, as they may require an alteration to antiparkinsonian medication:
  • Dystonic pain. See the Parkinson's UK information sheet Muscle cramps and dystonia
  • Primary or central neuropathic pain
  • Akathisia-related pain

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• All people affected by PD should be involved in deciding their treatment and care. Choice of treatment should suit the patient's needs and preferences, considering potential side effects and advantages.

Is drug therapy tailored to the individual?

The main aims of drug treatment are to:

• maximise function
• control symptoms
• keep the medication regime as simple as possible
• aid adherence
• reduce the likelihood of side effects as far as possible

Agree the plan

• It is important that lifestyle, amount of support at home and individual preferences are all taken into consideration
• Any medication changes should be shared and agreed with the individual (as a written and/or verbal plan), especially as dose timing is important
• Offer non-pharmacological approaches for the management of non-motor symptoms, e.g. dietary modifications for constipation

Decision support tools

• self-management/support tools
• clinician decision aids

Non-motor symptoms of Parkinson's | Parkinson's UK (parkinsons.org.uk)

NMS questionnaire.pdf (parkinsons.org.uk)

8.2 Mental Health Drugs

8.2.1 Hot Topic: Antidepressants

Treatment: Depression and anxiety disorders in adults aged 18 years and older

What is the aim of this hot topic and therapy?

To consider the management of depression and anxiety disorders, the use of non-pharmacological treatments and appropriate use of antidepressants including timely review and deprescribing.

Is this an essential medicine?

Essential medicines: for some people who have experienced severe and/or enduring mental illness. Such severe mental illness can be recurrent, debilitating, and potentially lethal.

Non-essential medicines: for the treatment of mild depression and/or anxiety, neuropathic pain associated with diabetes and other conditions.

Important benefits and risks of treatment, including any groups where specific considerations are required

Before starting antidepressant treatment, discuss with the individual, ensuring a person-centred approach with the individual:25^,105^{, [220]}

• the use of non-pharmacological treatment options first (see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027)
• if pharmacological treatment is to be used prescribers should:
• consider the benefits and risks of treatment taking into account the individual’s existing medications and comorbidities and the evidence base.
• inform the individual of the withdrawal (discontinuation) effects of antidepressants
• discuss the different adverse effect profiles of antidepressants and consider the positive and negative effects they would find beneficial or like to avoid
• discuss the likely response time to antidepressant treatment e.g. some show effect within one to two weeks for depression and set clear therapeutic goals
• discuss when treatment may need to be stopped

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

Depressive illness105^,132^,178^,220^, [221]^,[222]

Mild depressive illness

The risk–benefit ratio is poor for mild depression, therefore consider non-pharmacological options (see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027).105

A trial of antidepressant treatment may be appropriate for people with

• a history of moderate or severe depression
• initial presentation of sub-threshold depressive symptoms existing over a long period (typically at least two years)
• sub-threshold depressive symptoms or mild depression that persists after other interventions

Moderate to severe depressive illness

The use of antidepressants in combination with psychological therapies e.g. cognitive behavioural therapy (CBT) is more effective, with lower discontinuation rates, than treatment with antidepressants alone. (See NHS inform for CBT resources.)

Monitor efficacy and individual’s response, and if:

• no response to antidepressant at two to four weeks (citalopram, fluoxetine, paroxetine 20mg/day, escitalopram 10mg/day, sertraline 50mg/day, mirtazapine 30mg/day)
  • review diagnosis
  • check adherence with antidepressant dose and frequency
  • consider changing to another selective serotonin re-uptake inhibitor (SSRI) or other antidepressant, and review in two to four weeks
• partial response at four weeks:
  • consider revisiting/discussing the addition of non-pharmacological treatments (e.g. physical activity, CBT)
  • for mirtazapine, serotonin and norepinephrine reuptake inhibitors (SNRIs), lofepramine consider increasing dose, if tolerated
  • SSRIs demonstrate a flat dose-response effect for efficacy (citalopram, fluoxetine, paroxetine 20mg/day, escitalopram 10mg/day, sertraline 50mg/day). If no significant improvement it may be more appropriate to change the antidepressant rather than increase the dose

Chronic or recurring depression

For people who are at significant risk of relapse or have a history of recurrent depression, discuss treatments to reduce the risk of recurrence, such as continuing medication, augmentation of medication or psychological treatment (e.g. CBT). Treatment choice should be influenced by:

• previous treatment history, response to previous treatment and any discontinuation symptoms including the consequences of a relapse
• residual symptoms
• the individual’s preference

Depression in dementia

Non-pharmacological management of symptoms of stress and distress in dementia should be considered and implemented as first line approaches.

Antidepressants demonstrate limited benefits in treating depression in people with dementia. For some individuals, however, they may reduce depressive symptoms and improve general functioning. Sertraline, citalopram and trazodone have been used and are associated with modest reductions in symptoms of stress and distress in dementia.

Anxiety disorders: generalised anxiety disorder, panic disorder and obsessive compulsive disorders178^,212^,221^, [223]^,[224]

Mild anxiety disorders

Consider non-pharmacological options as the effectiveness of antidepressants in mild anxiety disorders is uncertain (see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027).105

Moderate to severe anxiety disorders

Antidepressants have been shown to be effective in the treatment of a range of moderate to severe anxiety disorders.

SSRIs and SNRIs are used, with SSRIs as first line pharmacological agents, due to their efficacy and safety profile, in the treatment of generalised anxiety disorders (GAD), panic disorders and obsessive-compulsive disorder (OCD). Tricyclic antidepressants can be effective in some anxiety disorders, but their use is limited due to the side-effect profile.

Monitor efficacy and response to treatment, if:

• no response to treatment consider:
  • in OCD increasing the antidepressant dose or offer an alternative antidepressant from a different class
  • in GAD offer high intensity psychological intervention or an alternative antidepressant from a different class
• partial response to treatment:
  • in GAD offer a high intensity psychological intervention in addition to their antidepressant
  • in OCD offer CBT in addition to an antidepressant

When medicines should not be stopped

Antidepressants should not be stopped abruptly especially in individuals with:

• previous discontinuation/withdrawal effects e.g. electric shock sensations, prickling sensations - slow managed reduction may be more appropriate
• history of severe and enduring illness – suddenly stopping treatment may lead to a deterioration in mental stability and/or withdrawal effects. Planned medicines reduction should be agreed between the individual and their prescriber

Safety - specific medication safety issues to highlight

Antidepressants:²¹²

• are associated with hyponatraemia, particularly in older people. Consider in all individuals who develop drowsiness, confusion or convulsions
• are associated with an increased falls risk in older people
• tricyclic antidepressants, high dose citalopram and high dose escitalopram can prolong QTc especially when combined with other medicines that affect cardiac rhythm

Discontinuation or withdrawal effects:

• paroxetine or venlafaxine are more commonly associated with discontinuation or withdrawal effects, especially when stopped suddenly
• some individuals may be more sensitive to discontinuation or withdrawal effects than others
• those people receiving higher doses and/or longer-term treatment may require slower reductions

SSRIs:212^,223

• increased risk of gastrointestinal (GI) bleeds, especially for older adults and those receiving medicines associated with GI bleeds (anti-inflammatory, antiplatelets and anticoagulants). Consider GI protection
• restlessness can occur when starting/increasing SSRI doses and usually settles within the first 10 days.
• can contribute to thoughts of suicidal/self-harm for a small minority of individuals with under 30 years olds being at greater risk

How and when to reduce and stop medication – deprescribing

Reducing or stopping antidepressants should done gradually and be considered when:

• treatment is ineffective
• therapeutic goals have not been achieved and an alternative approach is required
• treatment course is complete e.g.
  • first episode of moderate to severe depression - after six-month course
  • anxiety – after 12-month course
• adverse effects are present, for example:
  • if significant or severe agitation/restlessness (akathisia) develops, although very rare

When stopping antidepressant medicines consider:178^,220

• individual’s preferences, needs and experience of withdrawing antidepressant medication if applicable
• urgency of withdrawal
• half-life and duration of treatment. Those with a short half-life (e.g. paroxetine/venlafaxine) may need to be tapered more slowly and require more reduction steps
• severity of the withdrawal symptoms. If severe consider:
  • reinstating the previous antidepressant dose
  • re-attempting dose reduction after symptoms have resolved
  • reducing at slower rate with smaller reductions

For further detailed information on deprescribing antidepressants, see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027 under “reducing and stopping antidepressants”.105

Supporting people who do not or cannot reduce/stop

For some individuals it may not be appropriate to stop when:

• they have not completed the course of treatment
• longer term treatment may be required due to:
  • repeated depressive episodes
  • generalised anxiety disorder with repeated relapse
  • neuropathic pain
  • where the continuing treatment in the medium term may be appropriate due to individual circumstances, e.g. recent stress/bereavement

If stopping treatment is not feasible consider the range of options for reducing as outlined in Quality prescribing for antidepressants: guide for improvement 2024 to 2027.105

Specific areas/situations where medication may need to be introduced or increased

Antidepressant medication may need to be reintroduced or increased when:

• individuals experience recurrence or withdrawal symptoms. The previous lowest tolerated dose should be prescribed
• therapeutic goals are not achieved

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risks and benefits?

• Discuss reducing/stopping treatment in a supportive environment (including concerns of relapse)

Is drug therapy tailored to the individual?

• When supporting the individual through the reduction process, reassure them that withdrawal symptoms:
• are being monitored. If symptoms are severe, consider reinstating their previous antidepressant dose and frequency of administration
• are not a relapse of their depression and/or anxiety (as relapse does not usually occur within one to two weeks of stopping an antidepressant)

should gradually improve for most people, but some may experience longer term effects

Agree the plan

• Agree the dose change (share a written and/or verbal plan)
• Discuss non-pharmacological options
• Give information on self-monitoring and what to do if symptoms re-occur
• Continue regular review, whether treatment changing or remaining the same
• therapeutic aims still being met, e.g. no deterioration in symptoms
• there is no medication related harm requiring a change/reduction in treatment

individual circumstances have not changed, e.g. treatment course complete and therefore the individual may be ready to stop

Decision support tools

• self-management/support tools
• decision aids

Get help with your mental health and wellbeing on NHS inform (includes links to SilverCloud® (mental wellbeing courses), Daylight® (digital CBT), Sleepio® (digital CBT))

National Therapeutic Indicators for this hot topic

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Adults prescribed antidepressant medications long-term (>= 2 years) as a proportion of adults in receipt of antidepressant medications see Chart 4
• People receiving three or more of benzodiazepine/z-drug, opioid (including tramadol), gabapentinoid, antidepressant or antipsychotic (excluding depots)
• Mental health (GI bleed): number of people prescribed SSRI plus another medication known to increase risk of GI bleed without gastro-protection
• Mental health (long-term BZ with antidepressant): Number of people prescribed benzodiazepine or z-drug (for more than eight weeks) with an antidepressant

8.2.2 Hot Topic: Benzodiazepines and z-drugs

What is the aim of this hot topic and therapy?

To consider the management of insomnia and anxiety in adults, the use of non-pharmacological treatments and appropriate use of benzodiazepines and z-drugs (B-Z) including timely review and deprescribing.

Is this an essential medicine?

Essential medicines: benzodiazepines for alcohol or drug withdrawal, multiple sclerosis, intractable epilepsy, palliative care, or premedication for anaesthesia.

Non-essential medicines in most cases:

• z-drugs: long-term use (more than four weeks) in insomnia
• benzodiazepines: long-term use (more than four weeks) in insomnia, anxiety and back pain

Important benefits and risks of treatment, including any groups where specific considerations are required

Prior to starting, discuss with the individual, using a person-centred approach the:

• potential underlying causes of insomnia (e.g. pain, dyspnoea, anxiety)²¹²
• use of non-pharmacological options, (see NHS Inform, National Wellbeing Hub):
  • insomnia: consider sleep hygiene (e.g. caffeine reduction), use of a sleep improvement programme (e.g. “Sleepio®”)
  • anxiety: use of an anxiety improvement programme (e.g. “Daylight®”)

If B-Z are to be used, the benefits and risks of treatment must be balanced and therapeutic objectives agreed:

• may be effective for the short-term treatment of insomnia, and/or anxiety disorders but use should be limited to less than two weeks on an ‘as required’ basis. They are licensed for a maximum of four weeks only³⁰
• are associated with risks and avoidable harms:³⁰
  • falls, cognitive dysfunction, and increased mortality in some populations
  • dependence. Assess risk factors such as history of drug/alcohol misuse
  • tolerance and a loss of effect within two to four weeks of treatment withdrawal symptoms and potential difficulties in stopping these medicines

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

The use of B-Z can lead to increased risk of avoidable adverse effects, dependence and tolerance. The lowest effective dose for the shortest period should be used. Review effectiveness and tolerability on a regular basis.

Effectiveness of B-Z in insomnia

• should only be used to treat insomnia when it is severe, disabling, or causing the individual extreme distress, when underlying causes have been ruled out and when non-pharmacological measures have been ineffective
• may be effective when used short-term (maximum four weeks) for insomnia
• should be used on an ‘as needed’ basis²¹²

Studies assessing the effectiveness of B-Z, mainly assessment of seven days or less of treatment of insomnia, showed the effects were small, with an increased risk of adverse effects. The number needed to treat (NNT) for improved sleep quality was 13 and the number needed to harm (NNH) for any adverse effect was six.³⁰

Effectiveness of benzodiazepines in anxiety

• Evidence based psychological interventions are recommended as first line treatment ^[225]
• Benzodiazepines are indicated for the short-term (two weeks) relief in severe anxiety, which is disabling, or causing the person unacceptable distress either alone or when associated with insomnia²¹²
• They should not be used routinely and only when specifically indicated

Effectiveness of benzodiazepines in anxiety disorders

Include generalised anxiety disorder (GAD), panic disorder, social anxiety and post-traumatic stress disorder (PTSD).

Table 27: Effectiveness of benzodiazepines in anxiety disorders

Indication

Generalised Anxiety Disorder

Effectiveness

Benzodiazepines may be useful in the short-term management of GAD but are addictive and may cause harm. NICE recommends benzodiazepines should not be used in individuals with GAD except as a short-term measure during crisis.223

Indication

Panic disorder

Effectiveness

Benzodiazepines may be used in panic disorders (with or without agoraphobia) resistant to antidepressant treatment.212 NICE recommends that benzodiazepines should not be prescribed for panic disorders as they are associated with less good outcomes in the long term.223

Indication

Social anxiety disorder

Effectiveness

NICE recommends that benzodiazepines should not be used routinely in social anxiety disorder in adults. ^[226]

Indication

Post Traumatic Stress Disorder

Effectiveness

Evidence shows lack of benefit and potential of harm when benzodiazepines are used in the treatment of PTSD.178

When medicines should not be stopped?

Benzodiazepines should not be stopped abruptly without specialist advice in individuals taking them for indications such as multiple sclerosis, intractable epilepsy, alcohol or drug withdrawal or palliative care.

Safety - specific medication safety issues to highlight

B-Z use (list is not exhaustive):30^{, [227]}

• can cause respiratory depression
• is associated with a higher mortality risk for people with schizophrenia
• should be avoided in the older person as they are at greater risk of becoming ataxic and confused, leading to falls and injury
• is associated with an increased incidence of depressive symptoms
• can have negative effects on cognition (e.g. amnesia) and may limit the efficacy of psychological therapies such as cognitive behavioural therapy (CBT)
• two or more benzodiazepines or combined with a z-drug can increase the ‘benzo-burden’ creating a synergistic effect leading to more avoidable medication related harm
• can cause paradoxical effects (e.g. increased anxiety, hostility and aggression)
• drivers need to be cautioned when taking these medicines. See:

• Drugs and driving: the law for information on hypnotics whilst driving
• Zolpidem: risk of drowsiness and reduced driving ability

How and when to reduce and stop medication – deprescribing30^, [228]

Practitioners should proactively review benzodiazepine use and need when individuals are stable and well. The following groups of people may be appropriate for proactive reviews:

• recently discharged from hospital on new B-Z
• receiving long-term treatment (≥eight weeks)
• high dose combination use: >30mg per day diazepam equivalent
• people receiving diazepam 10mg tablets – known as ‘blues’
• reporting/presenting with street/ non-prescribed benzodiazepine use
• receiving other psychotropic medicines e.g. antidepressants, antipsychotics, gabapentinoids
• older (≥65 years) and/or frail adults:
  • care home residents
  • people with dementia and/or receiving other medicines that may cause cognitive dysfunction
  • polypharmacy
  • higher risk of falls

Deprescribe benzodiazepine or z-drugs, if:

• no longer benefiting the person
• the person is experiencing adverse effects
• the person wants to stop taking the medicine

Follow deprescribing guidance see the benzodiazepine tapering tool from Quality prescribing for Benzodiazepines and z-drugs: guide for improvement 2024 to 2027.

Deprescribing notes:

• Abrupt cessation may cause confusion, toxic psychosis, convulsions or a condition resembling delirium tremens. Reduction should be gradual and tapered unless individual is experiencing serious adverse effects²¹²
• The rate of reduction should be tolerable to the individual and depends on the dose, duration of use, and the individual’s clinical response212
• Withdrawal symptoms may occur at any time and up to three weeks after stopping a long-acting benzodiazepine. Symptoms include insomnia, anxiety, depression, cognitive impairment and can be similar to the original complaint. Some withdrawal symptoms may continue for weeks or months after stopping212
• Risk of problems with withdrawal includes long duration of medicine use, high dose of medicine, history of withdrawal symptoms, history of problems associated with dependence²²⁸

Supporting people who do not or cannot reduce/stop

• Schedule more frequent reviews to detect and manage problems
• If a person is unsuccessful on their first attempt, they should be encouraged to try again ^[229]
• People who do not wish to stop taking B-Z should30^,229
  • be advised on the benefits of stopping with face-to-face educational interventions and for the advice to be documented
  • be listened to, and concerns about stopping addressed
  • not be pressurised
  • be reviewed later (consider adding a review date to the prescription)

Specific areas/situations where medication may need to be introduced or increased

Most people experience infrequent, mild or no withdrawal symptoms if the withdrawal is slow and tapered to their needs. However, if they do experience withdrawal, consider reverting to the previous dose that caused no withdrawal effects. Stabilise on the higher dose, then reduce more slowly, using smaller dose reduction steps (which may require the use of liquid preparations).³⁰

Supporting people through reduction and ongoing review of medication

• Ensure the individual is ready and supported during the reduction process
• Understand past experiences of withdrawal
• A gradual reduction at a pace that is agreed with the individual improves the chance that the process is tolerable and successful
• Provide information on self-monitoring and what to do if symptoms re-occur
• Offer a non-pharmacological management plan

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• Risk associated with B-Z use
• Discuss reducing/stopping treatment in a supportive environment (including fear of relapse)
• Importance of gradual reduction of treatment and informed of the risk of withdrawal symptoms on stopping

• Discuss Drugs and driving: the law for information on hypnotics whilst driving

Is drug therapy tailored to the individual?

• The individual’s preferences, values and needs should be considered

• Provide continual support during and after the withdrawal process, e.g. self-help groups

Agree the plan

• The reducing/stopping plan should be shared and agreed with the individual (as a written and/or verbal plan)
• Offer non-pharmacological approaches for the treatment of insomnia/anxiety

Decision support tools

• self-management/support tools
• decision aids

Quality prescribing for Benzodiazepines and z-drugs: guide for improvement 2024 to 2027

Get help with your mental health and wellbeing on NHS inform (includes links to SilverCloud® (mental wellbeing courses), Daylight® (digital CBT), Sleepio® (digital CBT))

EMPOWER brochures are effective at giving information to support individuals who wish to reduce or stop benzodiazepines and z-drugs.

National Therapeutic Indicators for this hot topic

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Number of people prescribed benzodiazepine or z-drug (for more than eight weeks) with an antidepressant see Chart 5
• Mental health (triple whammy): Number of people prescribed three or more high risk medicines
• Hypnotics and anxiolytics: doses per list size

8.2.3 Hot Topic: Managing dementia and cognitive enhancers

What is the aim of this hot topic and therapy?

Dementia is a progressive neurological condition that is currently irreversible.

This hot topic considers the appropriateness of therapy (acetylcholinesterase inhibitors (AChEI) and memantine) to manage dementia.

Medication can provide modest improvements in attention and function for people with dementia. They are generally well-tolerated, and most adverse effects are short-lived, and some can be managed with practical advice.

A thorough clinical assessment including delirium screening should be completed if there is increasing confusion, hallucinations, stress and distress behaviours. Review and consider environmental, social, physical and medication changes and other stressors such as acute intercurrent illness, pain, constipation. Include a review of all medicines with anticholinergic effects. Any changes or causes should be managed prior to initiating medication.

Is this an essential medicine?

• There is a good evidence base for non-pharmacological treatments to improve quality of life in all types of dementia132^,[230]
• The AChEI donepezil, rivastigmine and galantamine and the N-methyl-D-aspartate (NMDA) receptor antagonist, memantine can be an important part of the individual’s treatment to manage symptoms of dementia
• The evidence supports a delay in progression to 24-hour care from treatment with this group of medicines^[231]
• Cognitive enhancers do not delay the underlying progression of dementia. However, stopping established treatment may lead to loss of cognition or function which may not be regained if the medication is restarted. Current guidance emphasises that the medicines should not be stopped based on disease severity alone, as continuing benefits in function and reduction of stress and distress can be seen, even in severe disease. Therefore, the risks and benefits of deprescribing should be considered carefully
• Initiating and reviewing these medicines is a specialist role and includes relevant post diagnostic support (for Scotland see the Dementia Strategy for Scotland).^[232] It is important to understand the principles of prescribing the medicines and situations where a therapeutic trial of medication may be appropriate

Table 28: Dementia medication licensed and unlicensed indications

Medication	Licensed indication	Common unlicensed uses
Donepezil tablets, orodispersible tablets, oral solution	Mild to moderate dementia in Alzheimer’s disease	First line treatment in Lewy body dementia Mild to moderately severe dementia in Parkinson’s disease
Galantamine modified release capsules, oral solution	Mild to moderate dementia in Alzheimer’s disease	Mild to moderate Lewy body dementia when first line not tolerated Mild to moderately severe dementia in Parkinson’s disease
Rivastigmine transdermal patches	Mild to moderate dementia in Alzheimer’s disease	Mild to moderate dementia with Lewy bodies considered in severe dementia with Lewy bodies
Rivastigmine capsules, oral solution	Mild to moderate dementia in Alzheimer’s disease Mild to moderate dementia in Parkinson’s disease	Mild to moderate dementia with Lewy bodies considered in severe dementia with Lewy bodies
Memantine tablets, orodispersible tablets, oral solution	Moderate to severe dementia in Alzheimer’s disease	Severe Lewy body dementia when first line not tolerated

Important benefits and risks of treatment, including any groups where specific considerations are required

General considerations prior to commencing medication:

• Increasing confusion, hallucinations, stress and distress behaviours, should prompt a thorough clinical assessment including delirium screening, review of environmental, social, physical and other stressors, and review of all medicines with anticholinergic effects
• Acute intercurrent illness, pain, constipation or a change in environment or care, can precipitate increasing confusion and those causes should be managed
• Recent changes in doses, starting or stopping medicines for dementia can precipitate changes in symptoms or function

Benefits:

• These medicines have a modest effect on symptoms which may still be significant for individuals
• For those with dementia who have symptoms of stress and distress, memantine can be used as an add-on treatment. It is also an option for people who do not tolerate AChEI, or where disease progresses despite their use

Risks:

• When assessing disease severity, consider factors that could affect the assessment and interpretation of cognition132
  • physical, sensory or learning disabilities
  • communication difficulties
  • cultural or language differences
• Previously tolerated medication can cause problems as dementia progresses and people become more sensitive to adverse drug reactions
• · Specific side effects such as bradycardia or gastrointestinal side effects are known risks
• · For a person with dementia in severe distress, where other causes have been excluded, there may be a role for discussing with individual or (carer/ next of kin/ welfare power of attorney) whether a therapeutic trial of stopping AChEI or memantine is warranted. The risks of doing this need to be discussed.

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

• Once initiated, effectiveness of these medicines should be assessed in partnership with the individual and their representatives, and this assessment must be holistic. Consider what matters to them in terms of perceived benefit/stability and severity of side effects
• Indicators that may help inform decisions to continue or stop therapy include:
  • rate of cognitive decline
  • global presentation
  • functional ability
  • and/or reduction of behavioural symptoms of stress and distress

Standardised tests (e.g. mini mental state examination (MMSE)) may be undertaken to help inform decisions but should not be the sole driver for change. For example, deterioration from moderate to severe disease should not automatically result in medicines licensed for mild to moderate symptoms being withdrawn, as continuing benefits in function and reduction of stress and distress can be seen.

When medicines should not be stopped

• Stopping established treatment may lead to loss of cognition or function which may not be regained if the medication is restarted, so the risks and benefits of deprescribing should be considered carefully
• For intolerance of one AChEI, a switch to a second can be considered after the adverse effects have resolved. Adverse effects usually settle within a few days. Switching advice can be sought from specialists

Safety - specific medication safety issues to highlight

Acetylcholinesterase inhibitors

Gastrointestinal (GI) side effects

• These are common and can lead to weight loss. Review should include weight monitoring to highlight potential GI adverse effects
• Most occur soon after starting the medication and quickly subside
• New medicines to treat GI symptoms should be avoided with practical approaches being tried first, such as dose reduction or advice about eating small amounts more often
• For a person who is losing weight while on an AChEI (where other causes of weight loss have been excluded), a trial without the medication may be indicated, however this has the associated risk of loss of other functional abilities and so the decision must be carefully balanced

Cardiac conduction abnormalities

There is no consensus guidance on when to specifically stop. The risks and benefits of treatment should be assessed with the individual and/or carers.

Cardiac conditions that could be reasons not to start AChEI:

• second or third-degree heart block in a person without a pacemaker
• QT prolongation
• bradycardia of less than 50 beats per minute

In addition, use with caution in people with

• left bundle branch block
• trifascicular block

Review appropriateness of ongoing AChEI use should these conditions develop:

• any second-degree heart block
• third-degree heart block
• trifascicular block
• significant bradycardia (whether sinus or junctional – heart rate (HR) <50bpm), but if symptoms (dizzy turns/falls) then HR <60bpm

Assessment of radial pulse and blood pressure is recommended during medication review or in individuals who may be experiencing any of the cardiac conduction adverse drug effects. Falls/syncope, breathlessness or dizziness should prompt measurement of radial pulse and blood pressure.

Prescribe AChEI cautiously if pulse is between 50-60bpm and asymptomatic.

Other medicines that can cause bradycardia should be taken into consideration when prescribing AChEI:

• individuals on medicines such as beta-blockers, amiodarone, digoxin, rate-limiting calcium channel blockers (e.g. diltiazem, verapamil)
• if rate-limiting calcium channel blockers or beta-blockers are being used to treat hypertension, alternative antihypertensive agents might be considered to facilitate the introduction or continuation of AChEI

Although there are known cardiac side effects of AChEI, there is a trend towards better cardiac outcomes for people prescribed these.^[233]

Memantine

• Assessment of anticholinergic adverse effects of memantine would be appropriate in line with assessment of anticholinergic burden. As with other medicines, memantine may be less well tolerated as dementia progresses and people may become more sensitive to side effects

Where people do not tolerate these medicines due to side effects, it is appropriate to stop the medication.

How and when to reduce and stop medication – deprescribing

Discontinuing AChEI in those with dementia may result in a decline of cognitive function and greater functional impairment. It may be appropriate to discontinue when:

• the individual is sufficiently non-adherent with the medication that continued prescription of it would not be worthwhile
• Covert medication usage may mean AChEI are not prioritised. However, at the first sign of a significant deterioration after a therapeutic trial of stopping, consider a restart where the benefits of the treatment outweigh the risks
• the rate of cognitive, functional, and/or behavioural decline is greater on treatment than prior to treatment
• intolerable side effects experienced such as significant weight loss or increased agitation where the risks outweigh the benefits. The transdermal route may not resolve GI issues and if a trial of this shows no improvement, then consider stopping
• emerging comorbidities make the risk of continued use either unacceptable or futile (e.g. concurrent physical illness with contra-indications); or
• the individual's dementia or other conditions progress to a stage where there would be no clinically meaningful benefit from continued therapy (e.g. approaching end of life care due to dementia or another life-limiting condition)
• an individual and/or their welfare power of attorney and/or welfare guardian decide to stop after being appraised of the risks and benefits of continuation and discontinuation

How to stop:

• it is reasonable to reduce the dose for one week and then stop
• review within two weeks to ensure there has been either an improvement in symptoms of stress or distress, or no deterioration in functional ability
• if medication is restarted within two weeks there is less likelihood of irrecoverable loss of function
• acute illness may require immediate stop (e.g. if symptomatic bradycardia stopping donepezil 10mg may be preferable to reducing to 5mg)

Supporting people who do not or cannot reduce/stop

Stopping established treatment may lead to loss of cognition or function which may not be regained if the medication is restarted. Current guidance emphasises that the medicines should not be stopped based on disease severity alone, as continuing benefits in function and reduction of stress and distress can be seen, even in severe disease. Therefore, the risks and benefits of deprescribing should be considered carefully. By using a person-centred approach, consider the impact and expectations for disease progression for people with dementia and their carers before stopping medication. Consider the wishes of the person with dementia, where these can be articulated including their previous decisions regarding treatment.

Specific areas/situations where medication may need to be introduced or increased

Memantine can be introduced in addition to an AChEI without referral back to a specialist for a person with moderate or severe dementia.132 Current practice may vary.

Residents of care homes may have undiagnosed dementia. Making a diagnosis can be helpful for many reasons such as consideration of legal frameworks for support with health and financial welfare. Consideration of all pharmacological and non-pharmacological treatment options should be made at the point of diagnosis.

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• Discussion of medication choices with relevant welfare proxies (welfare power of attorney or welfare guardian) for people who lack capacity is essential to support collaborative decision-making
• The place of non-pharmacological interventions for stress and distress ^[234]

Is medication tailored to the individual?

• The condition itself (dementia) can impair adherence
• Strategies such as memory prompts, timers etc are available. Discuss with the individual, family and pharmacy team, what is achievable and likely to help
• Donepezil orodispersible tablets, memantine liquid and rivastigmine patches can be considered where there are swallowing difficulties that prevent use of plain tablets
• Where a person lacks capacity to decide whether to take medicines, consideration can be made to administer medicines covertly. Relevant best practice guidance should be followed^[235]

Agree the plan

• Information for patients (and carers if appropriate) can be found on Alzheimer Scotland website^[236] and the Choice and Medication website.[237] This includes information leaflets in a variety of formats about the medicines individually, and a ‘Handy Chart’ comparing the medicines for dementia [238]
• Other areas of life are affected by a diagnosis of dementia and in particular:
  • driving recommendations will be required as per DVLA guidance
  • early consideration by people with dementia of legal frameworks to support decision-making can save time (and money) later, e.g. financial and/or welfare power of attorney
  • future planning such as Anticipatory Care can be considered at any stage
• Additional support can include:
  • maintenance of wellbeing - eating prompts; medication prompts
  • maintenance of personal safety if living at home, e.g. fire/gas appliance safety

Decision support tools

• self-management/support tools
• clinical decision aids

The Choice and Medication website Handy Chart can be used to compare the medicines for dementia.²³⁸

8.2.4 Hot Topic: Antipsychotics

What is the aim of this hot topic and therapy?

To ensure that antipsychotic prescribing is appropriate, safe and withdrawal/reduction is tailored to the individual and their circumstances.

Antipsychotics are used in the management of mental health conditions, symptoms of stress and distress in dementia, and delirium in adults.

Is this an essential medicine?

If it is an essential medicine, the individual should understand the importance of continuing with the treatment

Essential medicines:

• Antipsychotics used in schizophrenia, bipolar disorder, other psychotic disorders and for adjunctive treatment of major depression. They should not be reduced or stopped without specialist advice.

Potentially non-essential indications include:

• Anxiety and/ or psychomotor agitation
• Symptoms of stress and distress in dementia (SSDD)
• Delirium

SSDD was previously referred to as behavioural and psychological symptoms of dementia (BPSD) based on psychiatric upset in dementia. The terminology in trials and the evidence base is BPSD.

Important benefits and risks of treatment, including any groups where specific considerations are required

Discuss and consider with the individual, next of kin or welfare guardian (dependent on individual capacity):

• potential factors contributing to symptoms, e.g. anticholinergic burden, infection, pain132^{, [239]}
• use of non-pharmacological interventions is advised, for example:
  • in psychosis and related disorders: combination of psychological therapies (e.g. cognitive behavioural therapy (CBT), family intervention, self-help groups), and social support ^[240]
  • in SSDD: before antipsychotics are prescribed, non-pharmacological measures must be tried. See Alzheimer’s Society: non-drug approaches to changes in mood and behaviour234
  • in delirium: non-pharmacological measures must be tried before antipsychotics are prescribed, e.g. use of verbal and non-verbal de-escalation techniques²³⁹

If antipsychotics are required:

• agree the therapeutic objectives, balancing benefits and risks of treatment
• discuss the evidence base of antipsychotic use
• consider existing medications, comorbidities, adverse effects and risk factors
• use the lowest effective dose for the shortest time-period, except in life-long psychotic illness212
• follow local guidance for baseline and regular monitoring of the individual’s physical health, e.g. blood pressure and pulse, weight, HbA1c, blood tests.178^,212^,240

Medication effectiveness – when should this be considered and why, i.e. efficacy, individual choice, side effects

Regular monitoring of efficacy and safety of treatment is needed e.g. for SSDD in care homes:

• assess the reduction in the number of stress and distress incidents per week or month
• obtain qualitative feedback from relatives and/or care staff on the individual

Antipsychotics in mental health

Antipsychotics are used in a range of mental health conditions such as schizophrenia (acute and maintenance treatment) and other psychotic disorders, bipolar disorder and treatment resistant or severe depression.²¹²

The choice of antipsychotic should consider individual preferences, licensed indication, efficacy, side-effect profile, tolerability and person characteristics. For example, if there is a high risk of diabetes or the individual is overweight, it may be appropriate to initiate an antipsychotic with lower risk of weight gain and cardiometabolic effects.178^,212^,240

Antipsychotic doses should not be reduced or stopped without specialist advice, unless an individual is experiencing a medical emergency (e.g. neuroleptic malignant syndrome) or significant adverse drug reactions (ADRs).

Table 29: Antipsychotics in symptoms of stress and distress in dementia and delirium

Indication	UK licensed medication	Risks	Other
Symptoms of stress and distress in dementia	Haloperidol - Might show some effectiveness [241] [Persistent aggression and psychotic symptoms in moderate to severe Alzheimer’s dementia and vascular dementia unresponsive to non-pharmacological treatment]212 Risperidone - Modest effectiveness178 [Short-term treatment (up to six weeks) of persistent aggression in patients with moderate to severe Alzheimer’s dementia unresponsive to non-pharmacological treatment]212	Increased risk of adverse events. (e.g. increased risk of QT prolongation)212 Haloperidol is contra-indicated in people with Parkinson’s disease and Lewy body dementia132 Antipsychotics can worsen motor features in Lewy body or Parkinson’s disease, dementia, and in some cases cause severe antipsychotic sensitivity reactions132	Use with caution. Only use when there is a risk of harm to the individual or those living with them or are experiencing symptoms that are causing them severe distress132,212 Use at lowest effective dose for shortest time. Review regularly; at least every six weeks (earlier for in-patients)212
Acute delirium	Haloperidol - No robust evidence on effectiveness178,[242] [Acute delirium when non-pharmacological options ineffective]212	Risks as above	Use with caution. Use lowest effective dose for shortest time

Antipsychotics in palliative care

Refer to Scottish palliative care guidelines.169

When medicines should not be stopped

Seek specialist advice in

• schizophrenia, persistent delusional disorder, psychotic depression, bipolar affective disorder, or treatment resistant and/or severe depression ^[243]
• individuals who have had repeated unsuccessful deprescribing attempts243

Safety-specific medication safety issues to highlight

• older adults with dementia: increased risk of cerebrovascular adverse events and greater mortality ^[244]
• adults with pre-existing stroke risk factors²⁴⁴
• cardiometabolic risk: identify, monitor and manage modifiable risk factors²⁴⁴
• risk factors for venous thromboembolic events should be identified and prevented²⁴⁴
• individuals taking clozapine:
  • bowel obstruction due to paralysis of bowel wall may occur²⁴⁴
  • regular monitoring required due to increased risk of toxicity²⁴⁴
  • if dose is missed for more than 48 hours, re-titration required. Contact local mental health pharmacist/specialists for further advice
• follow local guidance for baseline and regular monitoring of the individual’s physical health, e.g. blood pressure and pulse, weight, HbA1c, blood tests178^,212^,240

How and when to reduce and stop medication – deprescribing

Reducing or stopping antipsychotic medications should be considered in individuals:

• with no valid indication ^[245]
• who experience clinically significant side effects²⁴⁵
• with poor adherence to oral treatment, consider alternative preparations if appropriate245
• who are not responsive to treatment after an adequate trial on optimal dose245

In addition, in psychosis, agitation, persistent aggression in SSDD:

• review at least every six weeks to check whether medication is still needed
• consider deprescribing within three months of initiation132^{, [246]}

Deprescribing notes

• Record reasons for continuing, stopping or reducing doses of medication
• Stop antipsychotic immediately if serious adverse effects occur
• Slower tapering may be required for those with severe SSDD or on long-term antipsychotics
• For a period after discontinuation regularly assess for symptom re-emergence
• Consider pausing planned reduction if there is a change in individual circumstances until situation settles, e.g. move of care setting, intercurrent illness, requirement for infection control isolation

Supporting people who do not or cannot reduce/stop

It is sometimes difficult to reduce or stop antipsychotics, and support is required243

Ensure individual and/or carer understands the risks and benefits of treatment, and that these may change over time, therefore ensure regular review.

Specific areas/situations where medication may need to be introduced or increased

In individuals who experience recurrent or withdrawal symptoms, the previous lowest tolerated dose should be prescribed.241

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• Reducing/stopping antipsychotics should employ a person-centred and shared decision-making approach
• The individual is advised not to stop abruptly due to the risk of withdrawal symptoms
• Provide information on self-monitoring and what to do if symptoms re-occur

Is drug therapy tailored to the individual?

• The individual’s preferences, values and needs should be considered
• Ensure the individual is supported during a gradual reduction process, as this improves the acceptability
• Ensure the reduction is at the right time for the individual
• Understand past experiences of withdrawal

Agree the plan

• Offer a non-pharmacological management plan
• The reducing/stopping plan should be shared and agreed with the individual and/ or carers (written and/or verbal plan).

Decision support tools

• self-management/ support tools
• decision aids

NICE Decision Aid: Antipsychotic medicines for treating agitation, aggression and distress in people living with dementia

Health Improvement Scotland: Delirium Toolkit

National Therapeutic Indicators for this hot topic

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Number of people aged 75 years and over prescribed an antipsychotic as a percentage of all people aged 75 years and over see Chart 6
• People receiving three or more of benzodiazepine/z-drug, opioid (including tramadol), gabapentinoid, antidepressant or antipsychotic (excluding depots)

8.3 Antimicrobial stewardship

8.3.1 Hot Topic: Penicillin allergy and de-labelling

What is the aim of this hot topic and therapy?

Approximately 10% of people identify as having a penicillin allergy, however true penicillin allergy is estimated to affect only one percent of the population.^[248] Symptoms of allergy can range from mild itch to severe and life-threatening anaphylaxis. If an adverse reaction to penicillin is suspected, it is critical that a clear account is obtained and documented.

Allergy can be defined by type:

Type I reaction (usually within one hour of administration):

• itchy rash
• facial/throat swelling
• breathing difficulties
• collapse

Type IV reaction (delayed reactions and usually occur 24-72 hours after administration):

• rash with blistering
• oral or genital ulceration or blistering
• rash associated with a severe systemic illness requiring admission to hospital

If an individual experiences type I or type IV reactions, it is an absolute contra-indication to further prescriptions.

The following should be considered as adverse reactions, but not allergic reaction:

• nausea and vomiting
• diarrhoea
• abdominal pain

As a result of an incorrect penicillin allergy label, individuals may receive alternative, less effective antibiotics, or antibiotics that are more likely to be associated with adverse effects or increased risk of antimicrobial resistance (AMR). ^[249]

This topic describes penicillin allergy and the process of de-labelling this allergy where appropriate.

Is this an essential medicine?

Antibiotics are commonly prescribed medicines essential for the treatment and prevention of bacterial infections. More than 83% of antibiotics are prescribed in a primary care setting ^[250] and at any one time approximately one in three patients in hospital receive an antibiotic. Penicillin antibiotics are highly effective and are the preferred first line treatment in many bacterial infections.

AMR arises when micro-organisms, such as bacteria, develop the ability to withstand antimicrobial treatments making infections harder to treat. AMR is associated with more severe disease and higher mortality.249 To slow resistance development it is important to ensure antibiotics are prescribed appropriately and use the narrowest spectrum antibiotic which will be effective.

Important benefits and risks of treatment, including any groups where specific considerations are required

A penicillin allergy label is associated with:[251]^,[252]

• increased morbidity (side effects, and drug interactions)
• greater healthcare costs due to longer hospital stays, increased readmission rates, and more critical care admissions
• increased risk of post-surgical wound infections
• Increased risk of reactions pre-operatively (to teicoplanin)
• increased rates of methicillin resistant Staphylococcus aureus (MRSA), Clostridium difficile (C. diff), and vancomycin-resistant Enterococcus (VRE) infection

This is most likely through use of broad-spectrum alternatives rather than ‘best first-line’ antimicrobial therapy.

It is essential therefore that individuals who have a potentially incorrect penicillin allergy label are fully assessed to confirm if they are truly allergic or not.

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

To determine whether an individual has a penicillin allergy, consider description of the reaction:

• which antibiotic did the reaction occur with?
• did this reaction result in hospitalisation or was emergency treatment required?
• if a rash was present, then
  • describe the rash
  • could it be related to an underlying condition, e.g. viral?
  • how long after administration did the rash appear?
• how long after administration did the reaction occur? Note reactions can be immediate or up to 30 days afterwards
• how long ago did the adverse reaction occur?
• what was the route of administration?

• did the reaction resolve on stopping the antibiotic? If so, what happened after stopping the drug?
• have they tolerated penicillin-based antibiotics (e.g. amoxicillin) since the initial recorded reaction?

If an individual had a reaction to an antibiotic, including penicillin, document:

• the antibiotic and route administered (e.g. oral or intravenous)
• a description of reaction (timing and symptoms/signs)
• how quickly the reaction resolved

Recording this information can help decision-making if the individual requires antibiotics in the future.

Safety - specific medication safety issues to highlight

People with a type I or type IV reaction should carry an allergy card ^[253] to prevent inadvertent prescribing of a penicillin containing antibiotic, which contains the following information:

I have a penicillin allergy.

Please check that my medicine does not have penicillin in it (see over).

Reaction I had was:

On:

These antibiotics have penicillin in them:

• Penicillin (phenoxymethylpenicillin)
• Amoxicillin
• Ampicillin
• Benzylpenicillin
• Flucloxacillin
• Co-amoxiclav (Augmentin®)
• Piperacillin/tazobactam (Tazocin®)
• Pivmecillinam
• Temocillin
• Co-fluampicil (flucloxacillin and ampicillin)

People with a true penicillin allergy should avoid antibiotics with a similar structure (beta-lactam ring) e.g. cephalosporins, carbapenems

How and when to reduce and stop medication – deprescribing

If an individual experiences a true penicillin allergy the antibiotic should be stopped immediately.

People with anaphylaxis should be treated as an emergency (see resource from Resuscitation Council UK).

Supporting people through reduction and ongoing review of medication

For people who do not have a true penicillin allergy, it may be possible to consider supervised penicillin allergy de-labelling (PADL) oral challenge. PADL may be undertaken in a hospital setting after careful assessment of risk.

In circumstances where there is a very low probability of a penicillin allergy:

• the ‘allergy’ occurred more than 10 years ago and symptoms were poorly recalled
• were non-severe or GI in nature
• there were no symptoms to suggest type I (anaphylaxis) or type IV hypersensitivity

Following consent, individuals receive a supervised low dose of penicillin by personnel trained in anaphylaxis management and resuscitation and are closely monitored for one hour for signs of reaction.

PADL is a well-established process and is supported by national and international allergy groups and evaluated by the Scottish Antimicrobial Prescribing Group (SAPG).253

Performing PADL in primary care is not currently recommended. Access to PADL from primary care currently varies across Scotland and local referral routes, where developed, should be followed.

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• The nature of penicillin allergy should be discussed and clarified with the person to optimise future care and reduce risk of adverse effects to non-penicillin antibiotics (if non-allergic), and allergic reactions, if true allergy
• If there is not a true penicillin allergy, the risk of a less appropriate antibiotic being used
• By removing a penicillin allergy label, does the individual understand that they can take penicillin-based antibiotics in the future?

Agree the plan

• The nature of the allergy or details of the allergy de-labelling should be recorded in the individual’s medical records and shared with primary care, health care professionals and family involved in their care

Decision support tools

• self-management/support tools

• decision aids

The SAPG has developed a penicillin allergy de-labelling pathway and toolkit for use in secondary care. The toolkit includes information and resources to support individuals.

8.3.2 Hot Topic: Antibiotic use at end-of-life

What is the aim of this hot topic and therapy?

The decision to start or not start antibiotic therapy, requires careful consideration as there are potential side effects, which may add to the symptom burden at end-of-life. Care is needed to ensure management aligns with what matters most to the individual to prevent care being overly medicalised. Clear goals and limits of therapy should be discussed.

Other medicines including mucolytics, muscle relaxants, analgesics, antipyretics and antitussives, can be used as alternatives for relief of infection-related symptoms.

Is this an essential medicine?

Antibiotics are one of the most prescribed medications and can be an essential treatment option for the prevention and treatment of infections. Approximately one in three patients in hospital receive an antibiotic but this is a small proportion of total antibiotics prescribed, as 83% are prescribed in a primary care setting.250 Long-term antibiotics should be reviewed as part of a 7-Steps polypharmacy review to ensure continued indication for their use.

Important benefits and risks of treatment, including any groups where specific considerations are required

Antimicrobial resistance (AMR) arises when micro-organisms, such as bacteria, develop the ability to withstand antimicrobial treatments making infections harder to treat which can result in severe disease and potentially death. To slow resistance, avoid the unnecessary use of antibiotics.

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

Anticipatory care plans should be created and clearly documented before the person becomes acutely unwell and can be used to make informed decisions about what matters to them. Shared decision-making about prescribing antibiotics towards the end of life should be taken jointly between the prescriber, wider multidisciplinary team and individual (and/or family/carers/welfare power of attorney as appropriate). This ensures the individual is aware of the potential benefits and risks, including when an antibiotic would or would not be prescribed.

When medicines should not be stopped

Antibiotics may be indicated to relieve symptoms or potentially cure an infection at the end-of-life, for example:

• a three-day course of appropriate antibiotics such as trimethoprim or nitrofurantoin will reduce the duration of symptoms of a lower urinary tract infection (UTI) in women
• treatment of painful conditions, such as cellulitis, candidiasis

The benefit of treatment of pneumonia at end-of-life is much less clear. Risks and benefits should be considered including when treatment would require hospitalisation, but individual preference is for end-of-life care at home.

Safety - specific medication safety issues to highlight

There are risks associated with giving antibiotics including side effects, e.g. oral or vaginal candidiasis, C. difficile infection and AMR.

Giving antibiotics intravenously is more invasive and increases the risk of secondary local infection.

How and when to reduce and stop medication – deprescribing

Antibiotic therapy should not routinely be escalated in the deteriorating individual at the end-of-life. If the antibiotic is not helping, is causing side effects or the individual wishes, it can be stopped.

Specific areas/situations where medication may need to be introduced or increased

Antibiotics may be introduced to relieve symptoms or potentially cure an infection.

Overall benefit for each individual should be the goal of any treatment as per General Medical Council’s ethical guidance summary Treatment and care towards the end of life.^[254]

Palliation of symptoms at end-of-life is of utmost importance. See the Scottish Palliative Care Guidelines - End of Life Care.169 SAPG provide further information and guidance on antibiotic use at end of life.

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• Is the individual able to take the antibiotic as prescribed or are other formulations/support required?

Is drug therapy tailored to the individual?

• Anticipatory care discussions with individual and family/carers should ideally take place long before the very final stages of decline.
• Future antibiotic prescribing decisions (including route of therapy) should be discussed, documented in the clinical notes and included in the individual’s Key Information Summary.

Agree the plan

• Individuals can continue to discuss ongoing treatment and plans should be reassessed if there are improvements or deterioration in the individual’s condition.

Decision support tools

• self-management/support tools
• decision aids

The four steps to anticipatory care planning can be found in the Healthcare Improvement Scotland Future Care Planning Toolkit and information for patients on future care planning is available on NHS inform.

8.4 Risks with combinations of high-risk medications

8.4.1 Hot Topic: High-risk combinations – Gastrointestinal (GI) bleeding concomitant use of non-steroidal anti-inflammatory drugs and selective serotonin re-uptake inhibitors

What is the aim of this hot topic and therapy?

This hot topic considers the impact of prescribing a non-steroidal anti-inflammatory drug (NSAID) and a selective serotonin re-uptake inhibitor (SSRI) at the same time and the increased risk of GI bleeding if these are taken together.223^{,[255],[256],[257]}

Is this an essential medicine?

Although not considered an essential medicine, stopping an SSRI antidepressant abruptly can cause discontinuation/withdrawal symptoms, such as dizziness/drowsiness, insomnia, irritability, headache, nausea and vomiting.

Important benefits and risks of treatment, including any groups where specific considerations are required

Pain and joint pain are the most common reason why NSAIDs may be prescribed.

SSRIs are mainly used for the management of anxiety and depression. Pharmacological and non-pharmacological approaches should be considered after diagnosis. Treatment should be reviewed regularly for effectiveness in the management of symptoms of both the pharmacological treatment and the psychological therapy.

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

Selective serotonin re-uptake inhibitors

The effectiveness of SSRIs needs to be reviewed (after one to two weeks, maximum four weeks) and switched to an alternative if this is not effective, rather than increasing the dose. The augmentation with non-pharmacological approaches should be considered.

Non-steroidal anti-inflammatory drugs

Joint pain is the most frequently cited reason for prescribing NSAIDs to those taking an SSRI. Before prescribing an NSAID for joint pain consider if an alternative option would be more appropriate. For example:

• exercise and physical activity can also contribute to a reduced need for medicines in osteoarthritis. This can also improve mood and well-being
• for patients with osteoarthritis the first-line medicines are paracetamol and/or topical analgesia, e.g. diclofenac and ibuprofen gels/sprays or capsaicin cream
• intra-articular injections of corticosteroids can be a useful alternative to oral NSAIDs for osteoarthritic flares in some patients
• a weak opioid, such as codeine, may be required for some patients if pain is ongoing or severe, for short-term use and with regular review
• for those with acute gout, colchicine may be considered. If colchicine not tolerated, corticosteroids (off-label) may be an alternative treatment option.^[258]

When medicines should not be stopped

Where possible, the NSAID should be stopped. If an NSAID is essential, then the shortest possible course should be used. GI protection with a proton pump inhibitor (PPI) may need to be considered, especially in older adults, who are at greater risk of SSRI-associated bleeding, or those with a history of GI bleed.

Safety – highlight specific medication safety issues

• The risk of GI bleeds and ulceration associated with NSAIDs is increased with e.g. corticosteroids, SSRIs, serotonin-noradrenaline reuptake inhibitors (SNRIs) (venlafaxine), antiplatelets (clopidogrel and ticlopidine), erlotinib, sibutramine, bisphosphonates or possibly alcohol[259]^,[260]
• Caution is advised in those receiving concomitant medications which could increase the risk of GI toxicity or bleeding, such as corticosteroids, anticoagulants such as warfarin, SSRIs or anti-platelet agents
• If GI bleeding or ulceration occurs in individuals receiving NSAIDs, treatment should be withdrawn immediately

How and when to reduce and stop medication – deprescribing

Selective serotonin re-uptake inhibitors (SSRIs)

• If depression has resolved, review the continued need for antidepressants
• Antidepressants should be decreased in a step-wise fashion to avoid any potential withdrawal reaction (see Quality prescribing for antidepressants: guide for improvement 2024 to 2027). The rate of reduction should be agreed and discussed with the individual
• Consider introducing non-pharmacological interventions if not already in place

NSAIDs

• NSAIDs do not need to be stopped gradually, but alternative treatments may need to be in place to support the individual

Supporting people who do not or cannot reduce/stop

• Consider use of PPI especially in those over 65 years
• Regular review of antidepressants
• Encourage non-pharmacological approaches, such as cognitive behavioural therapy (CBT) for depression/anxiety and physical activity for both depression and joint pain

Specific areas/situations where medication may need to be introduced or increased

• When reducing SSRI doses, individuals may experience withdrawal symptoms. It may be necessary to pause and review the withdrawal schedule (see Quality prescribing for antidepressants: guide for improvement 2024 to 2027)
• Depression can reoccur or the individual can have relapses. In these scenarios the antidepressant may need to be re-introduced at the lowest effective dose, along with non-pharmacological approaches. Other medicines the individual is on should be reviewed to ensure that there is no increased risk of harm due to combinations.

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risks and benefits?

• Use the shared decision-making tools to discuss the risks and benefits of the combinations
• By stopping the NSAID, the risk of GI bleeding is reduced

Is medication tailored to the individual?

• Ensure the individual and carers are aware of avoiding NSAIDs while taking SSRIs and discuss alternatives to manage pain

Agree the plan

• Review and agree the reduction plan
• Discuss non-pharmacological options to support mental health and well-being, and physical activity to manage pain
• Continue regular review, whether treatment changing or remaining the same

Decision support tools

• self-management/support tools
• decision aids

Get help with your mental health and wellbeing | NHS inform (includes links to SilverCloud® (mental wellbeing courses), Daylight® (digital CBT), Sleepio® (digital CBT))

National Therapeutic Indicators for this hot topic

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Percentage of people prescribed an SSRI in combination with antiplatelet, NSAID, Direct Acting Oral Anticoagulant (DOAC) or warfarin without gastro-protection as a proportion of all people prescribed an SSRI see Chart 7

8.4.2 Hot Topic: High-Risk Combinations - Use of combination blood thinners

What is the aim of this hot topic and therapy?

Blood thinning treatment is widely used as an effective therapy to lower the risk of a range of events. The aim of this section is to ensure that these are prescribed safely.

Is this an essential medicine?

Blood thinning treatment is effective in a variety of conditions with a range of magnitude of benefit.

The highest effect and most essential indications include:

• reduction of risk of clot in adults with metal heart valves^[261]
• initial treatment of pulmonary embolism^[262]
• antiplatelet treatment following coronary artery stenting[263]^,[264]

Important benefits and risks of treatment, including any groups where specific considerations are required

• Medication to reduce the blood's ability to clot are commonly used to reduce the risk of major adverse outcomes in a range of conditions:
  • heart attack (acute coronary syndromes)
  • stroke
  • pulmonary embolism (PE)
  • deep venous thrombosis (DVT)
  • atrial fibrillation (AF)^[265]
  • reducing clotting in adults with metal heart valves
• Medications that reduce the blood's ability to clot come in different drug classes
  • antiplatelets e.g. aspirin, clopidogrel
  • anticoagulants e.g. warfarin, or direct oral anticoagulants (DOACs) – e.g. apixaban, dabigatran, edoxaban, rivaroxaban
  • injected antithrombotics e.g. enoxaparin, dalteparin, fondaparinux
• Risk of bleeding
  • should always be balanced against potential benefit when prescribing blood thinning agents (see NNT table)
  • increases if more than one blood thinning agent is used at the same time
  • increases with age^[266]

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

• Risk of bleeding increases with age as well as the number of agents used
• Indication and duration should be clear both at commencing treatment and with continuing use
• Particular care is needed in ensuring that if an individual is on more than one blood thinning agent that:

• a clear indication exists and is still valid
• if the indication for more than one agent was time limited, that has not expired

• change in bleeding risk over time has not altered the risk/ benefit ratio

When medicines should not be stopped

Do not stop blood thinning medication or combination blood thinners in situations where the indication is clear, remains within specified duration, and bleeding risk has been considered, e.g. still within the recommended time post coronary artery stenting

Safety - specific medication safety issues to highlight

• When commencing treatment, both indication and duration of treatment should be clearly stated
• Combination blood thinners can be inappropriate in situations including:
  • An individual already on a blood thinner develops a second indication for a different blood thinner and two are prescribed rather than using one for both e.g.
    • an adult with previous stroke is prescribed clopidogrel then develops atrial fibrillation and is commenced on edoxaban. Clopidogrel should be stopped.
    • an adult with previous heart attack is prescribed aspirin and later develops a pulmonary embolism and is prescribed rivaroxaban. Aspirin should be stopped for duration of rivaroxaban treatment.
    • an adult is admitted to hospital with pneumonia and is prescribed enoxaparin to reduce the risk of DVT but is already on apixaban due to AF. Concomitant treatment with heparin agents and DOAC is contra-indicated
  • The indication for using more than one blood thinner was time limited and has elapsed e.g. an adult has a coronary artery stent inserted and required to be on dual antiplatelet treatment (DAPT) for 12 months but remains on it after this time. One of the antiplatelet drugs should stop[267]^,[268]
  • The indication for using more than one blood thinner is no longer common practice e.g.
    • adding an antiplatelet agent to an anticoagulant to reduce risk of stroke in an adult with AF is no longer current practice. Stop antiplatelet agent
    • using an anticoagulant to reduce stroke in an adult in sinus rhythm is no longer current practice. Use an antiplatelet agent instead

Managing bleeding risk:

• Ensure that bleeding risk is not increased by co-prescription of agents that increase risk of bleeding e.g.
  • non-steroidal anti-inflammatory drugs (NSAID)
  • selective serotonin re-uptake inhibitors (SSRI) antidepressants e.g. citalopram, fluoxetine
• Consider use of gastroprotection.^[269] Proton pump inhibitors are felt to be the most effective N.B. adults on clopidogrel should avoid omeprazole or esomeprazole

There is little randomised controlled trial evidence examining to what degree bleeding risk can be reduced by the addition of gastroprotection. ^[270] Guidelines and meta-analyses (largely based on observational trials) generally advise addition of gastroprotection if there is increased risk of bleed, including:

• use of high dose aspirin
• older age (consider in those over 65 years)
• history of gastroduodenal ulcer or perforation
• Helicobacter pylori infection
• concomitant use of medicines known to increase risk of gastrointestinal bleed
• use of one or more blood thinners

Consider effect of kidney function

• DOACs are affected by kidney function

• calculate creatinine clearance and adjust dose accordingly
• kidney function can improve as well as deteriorate so dose may need to increase or decrease
• at least annual assessment of kidney function is recommended while taking DOACs

How and when to reduce and stop medication - deprescribing

• If a blood thinning agent is no longer indicated or safe, it should be stopped. There is no need to reduce the dose before stopping
• If gastroprotection was started to reduce the risk of bleeding with a blood thinner and that blood thinner is then stopped, consider stopping gastroprotection

Supporting people who do not or cannot reduce/stop

• Advise on bleeding risk
• Provide alert card if taking oral anticoagulant
• Annually review benefit/risk
• Discuss importance of taking medication as prescribed

Specific areas/situations where medication may need to be introduced or increased

• DOACs are affected by kidney function e.g. apixaban, dabigatran, edoxaban, rivaroxaban. Therefore:
  • calculate creatinine clearance and adjust dose accordingly - refer to SPC^[271]
  • kidney function can improve as well as deteriorate so dose may need to increase or decrease
• A change in clinical condition will require review, e.g. development of AF
• A change requiring gastroprotection

Person-centredness: supporting collaborative decision-making and understanding Polypharmacy: Manage Medicines app

Does the person understand the outcomes of the review, including risk and benefits?

• DOACs thin the blood in a stable predictable way, so do not need blood tests for monitoring unlike agents such as warfarin

Is drug therapy tailored to the individual?

• To be effective, DOACs need to be taken at the same time each day. DOACs that are taken twice daily, e.g. apixaban need to be 12 hours apart

Agree the plan

• Adults on DOACs need at least annual review including renal function
• For adults on complicated regimens, repeated education and reminders may be required

Decision support tools

• self-management/support tools
• decision aids

HAS-BLED

CHA 2DS2VASC tool

ORBIT

8.4.3 Hot Topic: High Risk Combinations Acute Kidney Injury – Any three of metformin, NSAID, ACEI/ ARB, or diuretics

What is the aim of this hot topic and therapy?

This hot topic considers the impact of the triple whammy where any three of metformin, an ACEI (angiotensin-converting enzyme inhibitor), ARB (angiotensin II receptor blocker), NSAID (non-steroidal anti-inflammatory drug) and a diuretic are prescribed.

The purpose of this hot topic is to ensure that if they are prescribed in combination they are prescribed safely and appropriately. ^[272]

Is this an essential medicine?

ACEI/ARB may be essential for some individuals, particularly those with severe left ventricular systolic dysfunction.

Important benefits and risks of treatment, including any groups where specific considerations are required

ACEI/ARB and diuretics are commonly prescribed together, for example the management of heart failure or secondary prevention of cardiovascular disease (CVD). ACEI/ARB, with or without diuretics, are associated with an increased risk of acute kidney injury (AKI); the addition of NSAID significantly increases this risk; combining ACEI and ARB also significantly increases risk.

Due to the increased risk of lactic acidosis metformin should be prescribed with caution to people, with reduced renal function, if taking concomitant nephrotoxic drugs, or older adults.

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

Metformin ^[273]

The blood glucose-lowering effects of metformin may be enhanced by:

• ACEI

The blood glucose-lowering effects of metformin may be antagonised by:

• diuretics (thiazide and related, and loop)

NSAIDs

Joint pain is the most frequently cited reason for prescribing NSAIDs to individuals taking ACEI/ARBs with diuretics. Before prescribing an NSAID consider if an alternative option would be more appropriate. For example,

• exercise and physical activity can contribute to a reduced need for medicines in osteoarthritis
• in osteoarthritis the first-line medicines are paracetamol and/or topical analgesia, e.g. diclofenac and ibuprofen gels/sprays or capsaicin cream
• intra-articular injections of corticosteroids can be a useful alternative to oral NSAID for osteoarthritic flares in some individuals
• a weak opioid, such as codeine, may be required for some, if pain is ongoing or severe, for short-term use only and with regular review
• for those with gout, corticosteroids may be a safer option than NSAIDs for the treatment of acute flares when starting treatment with allopurinol, if colchicine is not tolerated.

When medicines should not be stopped

Where possible, NSAIDs should be stopped. If an NSAID is essential, then the shortest possible course should be used, and renal function reassessed regularly.

Safety – specific medication safety issues to highlight

ACEI/ARBs and other renin-angiotensin modifying agents can exacerbate AKI by reducing the kidney’s ability to adapt to changes in perfusion pressure.^[274]

Diuretics or other antihypertensives increase the risk of hypovolaemia/hypotension/ hyperkalaemia.^[275]

Risk factors for triple whammy-induced AKI are similar to other forms of kidney injury and include:272

• chronic kidney disease (CKD) eGFR less than 60 ml/min/1.73m²
• older age, e.g. over 75 years
• volume depletion due to, e.g. vomiting, diarrhoea, sepsis or low fluid intake
• diabetes
• heart failure
• liver disease

The combination of any three or more of metformin, NSAIDs, ACEI/ARBs or diuretic is a very high-risk combination - stop if you can, starting with NSAIDs.

All these medicines are associated with risk of renal impairment. Concurrent use of three or more of these drugs is likely to create a significant cumulative risk of AKI.

Also consider other medications that the individual may be taking that are nephrotoxic, e.g. aminoglycoside antibiotics, and iodinated contrast agents.^[276]

How and when to reduce and stop medication – deprescribing

NSAIDs do not need to be stopped gradually, but alternative analgesia may need to be in place to support the individual. Discuss Medication Sick Day Guidance with them and ensure that people taking the triple whammy combination, or the double whammy combination, know to avoid over the counter (OTC) products that contain NSAIDs, and use alternative analgesics.

Supporting people who do not or cannot reduce/stop

There are no guidelines for monitoring patients taking metformin, ACEI/ARB, a diuretic and an NSAID. A pragmatic approach is to take a baseline measurement of the person’s:

• body weight
• blood pressure
• serum creatinine and electrolytes
• HbA1c

A baseline measurement of serum creatinine is essential as it may be required later to diagnose AKI. Serum potassium may increase with the use of ACEI/ARB or NSAIDs, particularly as renal function declines, or decreases with volume depletion.

A follow-up assessment, with repeat weight, blood pressure, serum creatinine and electrolytes, within the first month of treatment may also be beneficial, due to the increased risk of AKI during this period. More frequent monitoring is required if they become acutely unwell.

Discuss Medication Sick Day Guidance and ensure that those taking the triple whammy combination, or the double whammy combination, know to avoid OTC products that contain NSAIDs using alternative analgesics and seek advice.

Specific areas/situations where medication may need to be introduced or increased

Medication does not need to be introduced, but need to ensure that there is avoidance of the prescribing cascade where additional medication needs to be added in to counteract the effects of the combinations below:

• ACEI/ARB, a diuretic and an NSAID: antihypertensives and diuretics may be less effective if they are concurrently prescribed with an NSAID^[277]
• when NSAIDs are taken with an ACEI/ARB, the blood pressure lowering effect of the ACEI/ARB is decreased
• when NSAIDs are taken with a diuretic, the effect of the diuretic is reduced, and any heart failure may be exacerbated
• there is an increased risk of cardiovascular events associated with all NSAIDs; a risk that is higher in older adults due to their increased baseline risk of a cardiovascular event

Person-centredness: supporting collaborative decision-making and understanding Polypharmacy: Manage Medicines website and app

Does the person understand the outcomes of the review, including risk and benefits?

• By stopping the NSAID, the risk of AKI, and the additional negative effects of the interaction with ACEI/ARB and/or diuretic are reduced

Is therapy tailored to the individual?

• Maintain a good fluid intake to avoid volume depletion, particularly if feeling unwell or in hot weather
• Discuss Medication Sick Day Guidance. If the individual becomes acutely unwell whilst taking the triple whammy combination, e.g. with vomiting or diarrhoea, advise them to:
• Stop taking the NSAID and use an alternative analgesic for pain relief or fever if required, e.g. paracetamol

Agree the plan

• Ensure that the individual understands the importance of taking alternative analgesia to NSAIDs
• Avoid inadvertently taking additional NSAIDs. Educate about the different types (oral and topical) and brand names of NSAIDs that are available, e.g. ensure that they know that Nurofen® and ibuprofen are the same medicine, and that diclofenac and naproxen are also NSAIDs

Decision support tools

• self-management/support tools
• decision aids

Medication Sick Day Guidance

National Therapeutic Indicators for this hot topic

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Number of people aged 65 years and over co-prescribed an NSAID and ACE inhibitor/angiotensin receptor blocker and diuretic, as a percentage of all people aged 65 years and over prescribed an ACE inhibitor/angiotensin receptor blocker and diuretic – see Chart 8
• Number of people aged 65 years and over co-prescribed an NSAID and ACE inhibitor/angiotensin receptor blocker and metformin, as a percentage of all people aged 65 years and over prescribed an ACE inhibitor/angiotensin receptor blocker and metformin

8.4.4 Hot Topic: High-risk combinations – Concomitant use of any three of opioids, benzodiazepines, z-drugs, gabapentinoids or antidepressants: Mental Health Triple Whammy

What is the aim of this hot topic and therapy?

This hot topic considers the impact of concurrent prescribing of any three of: opioids; benzodiazepines; z-drugs; gabapentinoids or antidepressants.154^,220^,228^,[278] This increases sedation, falls, severe respiratory depression, the potential for dependency and possible withdrawal reactions when these medicines are stopped.

Is this an essential medicine?

Benzodiazepines may be considered essential in people receiving them for certain conditions including alcohol or drug withdrawal, multiple sclerosis, intractable epilepsy, palliative care, or premedication for anaesthesia. They are not essential when used for the management of insomnia or anxiety.

Gabapentinoids if used for the management of epilepsy can be considered essential, but not for the management of pain.

Z-drugs, opioids and antidepressants are not regarded as essential medicines.

Although not considered essential medicines, stopping any of these medicines abruptly can cause discontinuation/withdrawal symptoms, such as dizziness/drowsiness, insomnia, irritability, headache, nausea and vomiting.

Important benefits and risks of treatment, including any groups where specific considerations are required

All of these medicines are associated with dependency and potential for withdrawal reactions and this should be discussed with the individual before initiation. The risk of harm increases with the increasing number of these medicines taken concurrently.^[279] Each has a risk of dependence, so there should be assessment of risk factors such as history of problem substance/alcohol use. Pharmacological and non-pharmacological approaches should be considered as treatment options and reviewed regularly for effectiveness.

Opioids are used for the management of acute pain. [280]^{, [281]} Due to lack of evidence for efficacy and evidence of significant long-term risks, they are not recommended long-term for the management of non-cancer chronic pain.

Antidepressants are mainly used for the management of anxiety and depression. They may also be used for the management of neuropathic pain.

Benzodiazepines and z-drugs are used for the short-term treatment of insomnia, and/or anxiety disorders but use should be limited to less than four weeks on an ‘as required’ basis, and the benefits and risks of treatment must be balanced and therapeutic objectives agreed. They are associated with:

• avoidable harm such as falls, cognitive dysfunction, and increased mortality in some populations
• dependence. Assess risk factors such as history of problem substance/alcohol use

Gabapentin and pregabalin are antiseizure medications but they are commonly used for the management of neuropathic pain and anxiety. However, they have a significant risk of adverse effects including drowsiness or somnolence, dizziness, nausea, weight changes (abnormal appetite), severe respiratory depression, cognition and speech problems/ataxia.^[282]

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

For each of these classes of medications, there should be review of the indication and on-going need. Augmentation with non-pharmacological approaches should be considered.

Antidepressants

The effectiveness of antidepressants needs to be reviewed (after one to two weeks, maximum four weeks) and switched to an alternative if this is not effective, rather than increasing the dose.

Opioids

Opioids are used for the management of acute pain. They should not be used long-term for the management of chronic pain.280^,281

• exercise and physical activity can contribute to a reduced need for medicines in osteoarthritis. This can improve mood and well-being
• for those with osteoarthritis the first-line medicines are paracetamol and/or topical analgesia, e.g. diclofenac and ibuprofen gels/sprays or capsaicin cream
• intra-articular injections of corticosteroids can be a useful alternative to oral NSAID for osteoarthritic flares in some individuals
• a weak opioid, such as codeine may be required for some people. If pain is ongoing and severe, consider a stronger opioid at the lowest effective dose to manage pain for short-term use and with regular review. Note that there is an increased risk of serotonin syndrome with SSRIs and tramadol, and also hyponatraemia

Gabapentinoids

• In the management of pain, they are licensed for the treatment of neuropathic pain
• Pregabalin is licensed for the management of generalised anxiety disorder
• Their use should be reviewed if prescribed for other indications

Benzodiazepines and z-drugs

These should only be used for short-term use and reduced and stopped after two to four weeks when used for non-essential purposes

When medicines should not be stopped

Where possible, when used for non-essential use, these medicines should be stopped. (See above for essential use where these medicines should not be stopped without specialist input).

Reduction of therapy should be controlled, not sudden, to manage the risk of withdrawal symptoms.

Successful reduction requires shared decision-making and the individual’s participation in a person-centred review that considers the personal context. A person-centred assessment of risk versus benefit should occur before reducing or stopping medication to determine the effectiveness of treatment.

Safety – highlight specific medication safety issues

• Before prescribing any of these medications, there should be a discussion about the potential risks of dependence and withdrawal.
• Very high-risk combination. Stop if you can. These combinations are associated with increased risk of respiratory depression, sedation and (in the case of antidepressants) serotonin syndrome.[283]^,[284]
• Only co-prescribe benzodiazepines with opioids if there is no alternative and, if necessary, the lowest possible doses should be given for the shortest duration.
• Monitor individuals closely for signs of respiratory depression at initiation of treatment and when there is any change in prescribing, such as dose adjustments or new interactions.

Gabapentinoids

Prescribers and individuals should be aware:

• Reduced renal function requires dose reduction to reduce risk of toxicity and side effects.
• MHRA has highlighted the risk of foetal abnormalities, and this should be discussed with people before initiation.

Antidepressants

• With SSRIs, caution is advised in those receiving concomitant medications which could increase the risk of gastrointestinal (GI) toxicity or bleeding (such as nonsteroidals and antiplatelets).^[285]

Opioids

• Higher doses have a greater risk of serious harm (four times higher for 50-100mg morphine equivalent dose (MED), nine times higher for doses greater than 100mg MED).
• Serious harms include overdose and death, opioid misuse, increased risk for falls and major trauma, and increased odds of road accident.168

How and when to reduce and stop medication – deprescribing

For each of these medicines, review the continued need. Assess if the condition has resolved.

If more than one medication needs to be stopped, ideally do this one at a time to avoid withdrawal reactions. If there is mixing with street-products then this may be done more rapidly due to increased risk of overdose.

• they should be decreased in a step-wise manner to avoid any potential withdrawal reaction (see Quality prescribing for antidepressants: guide for improvement 2024 to 2027).105 The rate of reduction should be agreed and discussed with the individual.
• consider introducing non-pharmacological interventions if not already in place.

Supporting people who do not or cannot reduce/stop

• Review continued need for medication and risks and harms of ongoing treatment.
• Encourage non-pharmacological approaches to support reduction where appropriate, such as CBT and physical activity

Specific areas/situations where medication may need to be introduced or increased

• When reducing doses of any of these medications, individuals may experience withdrawal symptoms. It may be necessary to pause and review the withdrawal schedule.
• Depression can reoccur or the individual can have relapses. In these scenarios the antidepressant may need to be re-introduced at the lowest effective dose, along with non-pharmacological approaches. Other medicines the individual is taking should be reviewed to ensure that there is no increased risk of harm due to combinations.

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risks and benefits?

• Use the shared decision-making tools to discuss the risks and benefits of the combinations.

Is drug therapy tailored to the individual?

• Ensure the individual and carers are aware of these risks of these medicines and their combination, discuss alternatives

Agree the plan

• Review and agree the reduction plan
• Discuss non-pharmacological options to support mental health and well-being, and physical activity to manage pain
• Continue regular review, whether treatment changing or remaining the same

Decision support tools

• self management/support tools
• decision aids

Reduction schedules for antidepressants

Reduction schedules for benzodiazepines and z-drugs

Reducing and stopping antipsychotics

National Therapeutic Indicators for this hot topic

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• People receiving three or more of benzodiazepine/z-drug, opioid (including tramadol), gabapentinoid, antidepressant or antipsychotic (excluding depots) see Chart 9

8.4.5 Hot Topic: Medication Sick Day Guidance

What is the aim of this hot topic and therapy?

There is a potential risk of harm to individuals taking certain medicines while experiencing a dehydrating illness (repeated vomiting or diarrhoea and/or fever, sweats and shaking). The aim of the Medication Sick Day Guidance is to prevent such adverse events by temporarily withholding medication during episodes of acute dehydrating illness and restarting once the individual is well. ^[286] The temporary cessation of medication should not normally be for longer than 72 hours without seeking advice from a healthcare professional.

Is this an essential medicine?

A person-centred approach should be used with the Medication Sick Day Guidance. Prior to provision, consider the individual’s risks and benefits of following the Medication Sick Day Guidance, as the guidance may not be suitable for some individuals, for example, those at risk of decompensating with left ventricular systolic dysfunction (LVSD).

Medication Sick Day Guidance may be appropriate for those taking one or more of the following medicines (and can be remembered with the SADMAN acronym):

• Sulfonylureas or sodium-glucose co-transporter-2 (SGLT-2) inhibitors
• Angiotensin-converting enzyme (ACE) inhibitors
• Diuretics
• Metformin
• Angiotensin receptor blockers (ARB)
• Non-steroidal anti-inflammatory drugs (NSAID)

Most medications will only be temporarily withheld until the individual has recovered, as they are required for the management of chronic conditions.25 ACE inhibitors and diuretics in non-LVSD presentations, and NSAIDs may not be classed as essential medicines as per Table 31.

This list is not exhaustive, and healthcare professionals (HCP) can add medicines to the alert card, if there are concerns that an individual may come to harm if a specific medicine is continued during an acute dehydrating illness.286^{, [287],[288]}

Important benefits and risks of treatment, including any groups where specific considerations are required

Generally:

• During dehydrating illness, the risk of acute kidney injury (AKI) may be increased by medications that lower blood pressure, reduce circulating volume or renal blood flow.
• The recommendation for temporary interruption of treatment is largely based on expert consensus and more research on the implementation and effectiveness of Medication Sick Day Guidance is required, particularly in the community setting. [289]^{,[290], [291], [292]}
• A person-centred approach should be used with Medication Sick Day Guidance. Targeted provision to those at high risk of AKI, based on an individual risk assessment may be a more suitable and pragmatic approach.292^,[293]
• In anticipation of a dehydrating illness, individuals at risk of AKI should be advised to seek healthcare professional advice on medication changes.^[294]
• The guidance may not be appropriate in those with moderate to severe LVSD, as these individuals can decompensate and require specialist management. Therefore, during dehydrating illness, it may be advisable to seek specialist advice for these individuals instead of providing Medication Sick Day Guidance.
• All individuals should be advised to contact a healthcare professional for review if acute illness persists for longer than 72 hours. For adults admitted to hospital, it is recommended that advice on when to restart medication should be included at discharge.

Medicine specific

• Sulfonylureas: continuing these during a dehydrating illness may increase the risk of hypoglycaemia, particularly if food and fluid intake are reduced.287
• SGLT-2 inhibitors:

• increase diuresis and may exacerbate volume depletion during intercurrent illness. SGLT-2 inhibitors should be taken with caution in people who have limited oral intake or severe dehydration. Withholding SGLT-2 inhibitors during dehydrating illness can be part of a diabetic ketoacidosis (DKA) prevention strategy.²⁰⁴
• can also be associated with euglycaemic DKA. When an individual is hospitalised for major surgery or acute serious medical illness, SGLT-2 inhibitors should be temporarily stopped, and blood ketones monitored during treatment interruption. Treatment may be restarted when the ketone values are normal and the individual’s condition has stabilised.206^,[295]

• ACEI, ARBs and NSAIDs may impair renal function and exacerbate acute kidney injury in those with intercurrent illness. Temporarily withholding ACEI and ARBs during dehydrating illness should be considered.286^,[296]1
• NSAIDs: careful consideration on their use to reduce fever in dehydrating illness should be balanced with the risk of AKI.

• Diuretics: can either directly cause dehydration or increase the likelihood of dehydration during intercurrent illness.25
• Metformin: reduced clearance can increase the risk of adverse effects, such as lactic acidosis.25^,289

Medication effectiveness – when should this be considered and why, i.e. efficacy, individual choice, side effects

During an acute dehydrating illness, medication review is advised and consider implementation of the Medication Sick Day Guidance where appropriate.

When medicines should not be stopped

Medication Sick Day Guidance is not always appropriate, for example, individuals with heart failure should discuss with their healthcare professional what they should do with their medicines in the event of a dehydrating illness.

Safety – highlight specific medication safety issues

Reasons to consider stopping temporarily

• Impaired renal function
• Dehydration
• DKA

• Adverse effects due to reduced medicine clearance (e.g. lactic acidosis)

Individuals at higher risk of temporarily stopping medication

• At risk of decompensating LVSD

How and when to reduce and stop medication – deprescribing

Medication Sick Day Guidance involves temporary suspension of the specified medicine during a dehydrating illness. Medicines should normally restart when the individual is back to their baseline function and eating and drinking normally. For a minor acute illness this could be a few days. For a more serious illness, for example with hospital admission, this may be weeks.

Advice on when to restart specific medication should be provided upon discharge for people who have been admitted to hospital.

Note that deprescribing is outwith the scope of Medication Sick Day Guidance but regular review of medicines to ensure their continued need and effectiveness is recommended.

Supporting people who do not or cannot reduce/stop

• Counsel on the importance of maintaining fluid balance during dehydrating illness
• Where necessary, counsel relatives/carers on Medication Sick Day Guidance²⁸⁶
• Counsel on signs and risks of AKI291 including nausea or vomiting, diarrhoea, dehydration, urinating less than usual, confusion or drowsiness^[297]
• Where appropriate, counsel on signs and risks of DKA291 including rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, fast and deep breathing, confusion, unusual sleepiness or tiredness, a sweet smell to the breath, a sweet or metallic taste in the mouth, or a different odour to urine or sweat^[298]

Specific areas/situations where medication may need to be introduced or increased

• Diagnosis of the cause of the dehydrating illness will guide appropriate management. A person-centred medicine review should be undertaken.
• Ensure individual/carer is clear about how and when to restart medication (if appropriate).

Person-centredness: supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• Perform a risk-benefit assessment to determine the suitability of the advice for the individual considering comorbidities
• Definition of dehydrating illness (repeated vomiting/ diarrhoea and/or fever, sweats and shaking)
• Minor illness or a single episode of sickness and diarrhoea does not merit treatment cessation
• The rationale for pausing certain medicines during dehydrating illness
• The name of the medicine(s) they should withhold
• Temporarily withholding medication should not normally be for greater than 72 hours without seeking advice from a healthcare professional
• Medicines should be restarted once eating and drinking normally for 24 to 48 hours and no longer acutely unwell

Is drug therapy tailored to the individual?

• Advise individuals unable to identify their medicines, for example in a compliance aid, to speak with their community pharmacy team. Written medication descriptions and large font labels on compliance aids can be beneficial

Agree the plan

• Provision of Medication Sick Day Guidance should have a person-centred approach
• Clear understanding of the information provided should be checked with the individual
• To help avoid inappropriate treatment cessation, complete the Medication Sick Day Guidance online form on the Polypharmacy: Manage Medicines website or app, to provide individuals with a personalised list of their medicines to withhold

Decision support tools

• self-management/support tools
• decision aids

The Medication Sick Day Guidance can be personalised with medicine names and an electronic copy saved, printed or emailed.

Further resources are available in Appendix F

The Health Literacy Place provides communication tools and techniques, such as ‘Teach Back’ and ‘Chunk and Check’, that can be helpful when counselling individuals on Medication Sick Day Guidance.

8.5 Other

8.5.1 Hot Topic: Osteoporosis

What is the aim of this hot topic and therapy?

To consider the appropriateness of antiresorptive therapy (e.g. bisphosphonates, denosumab) including duration to reduce fracture risk in the management of osteoporosis.

Is this an essential medicine?

Although not essential, consider the prescription of antiresorptive therapy to reduce the fracture risk when managing osteoporosis in postmenopausal women. Individuals who suffer hip and vertebral fractures (an important cause of morbidity) have a decreased life expectancy.109^, [299]^, [300]^, [301]^, [302]

Important benefits and risks of treatment, including any groups where specific considerations are required

Generally:

• Offer treatment to individuals at risk of new or recurrent osteoporotic fragility fractures (fractures resulting from low-level trauma)
• Encourage an adequate intake of calcium and vitamin D through the normal diet but supplements may be necessary if dietary calcium is low, or vitamin D insufficiency is a risk109^,212

Bisphosphonates:

• Including alendronic acid, risedronate sodium, ibandronic acid and zoledronic acid, can be prescribed for reducing fracture risk in the treatment of osteoporosis, and can reduce the risk of vertebral, non-vertebral or hip fractures109^,212^,299^,300^,301^,302^, [303]^, [304]^,[305]^, [306]^, [307]^, [308]^, [309]
• See NNT table for further detail
• Therapy is most likely to benefit those who have a life expectancy greater than 12.4 months,304 therefore consider likely life expectancy/prognosis when deciding whether to prescribe bisphosphonates for postmenopausal women with osteoporosis
• Oral bisphosphonates should be the first-line treatment therapy where appropriate for postmenopausal women and men over 50 years, at increased risk of fracture109^,299^,300^,301^,302^,303^,304
• Oral bisphosphonates should be prescribed for at least five years before reassessing risk, or at least three years302 for intravenous bisphosphonates
• Oral bisphosphonate can be prescribed for at least 10 years in people
  • over 70 years, with a previous history of a hip or vertebral fracture(s)
  • taking glucocorticoids equal or more than 7.5mg prednisolone per day (or equivalent)
  • who have experienced one or more fragility fractures during the first five years of treatment, when their treatment has not been changed302
• Zoledronic acid is an intravenous bisphosphonate which can be prescribed to prevent or reduce the risk of vertebral, non-vertebral and hip fractures in postmenopausal women who cannot tolerate oral bisphosphonates.109 It should be prescribed for at least three years in people over 70 years302
• Oral ibandronic acid can be considered for preventing vertebral fractures in postmenopausal women with osteoporosis109
• Ibandronic acid is not recommended to reduce non-vertebral or hip fracture risk300^,301
• Alendronic acid, risedronate sodium or zoledronic acid can be prescribed for prevention of vertebral fracture in men and women associated with glucocorticoid related risk109^,212
• Zoledronic acid can be prescribed for men in the treatment of osteoporosis for prevention of vertebral fractures.212
• Risks of bisphosphonate treatment are gastrointestinal (GI) upset and oesophageal erosion and ulcers, therefore use with caution in those with upper GI problems. Avoid use of alendronic acid and oral ibandronic acid in those with stricture or achalasia, however, risedronate can be used with caution109^,212
• When selecting drugs to reduce the risk of fractures in postmenopausal women, and men older than 50 years, alternative treatment options should be available if first-line bisphosphonates are unsuitable or not tolerated302

Denosumab:

• When bisphosphonates are contra-indicated or there is an intolerance, denosumab should be prescribed (if appropriate) to prevent vertebral, non-vertebral and hip fractures in postmenopausal women with dual-energy X-ray absorptiometry (DXA)-proven osteoporosis109
• When prescribing denosumab, serum calcium should be checked two weeks before treatment, and for individuals with renal impairment (eGFR <30ml/min), this should be checked again a fortnight after therapy.109 Individuals should be encouraged to report symptoms indicative of hypocalcaemia, such as muscle spasms or tingling in hands or face.
• Denosumab therapy should continue for five years and possibly up to 10 years if the individual is at high risk of fracture109^,300^,301^,302
• Denosumab prescribed in people older than 75 years can reduce the risk of new vertebral fractures, but not non-vertebral fractures [310]^, [311]
• When denosumab is discontinued, other antiresorptive therapy should be prescribed, for example, an intravenous infusion of zoledronic acid six months after the last dose (if bisphosphonates are not contra-indicated). This prevents the rebound increase in bone turnover, reducing the chance of rapid bone mineral density loss and increased fracture risk.³⁰²

Medication effectiveness – when should this be considered and why, i.e. efficacy, individual choice, side effects

Check on adherence to therapy as treatment benefits will not be obvious to individuals taking it. Healthcare professionals (HCP) should be aware that adherence to a range of treatments decreases over time.306 Bisphosphonates may be given weekly rather than daily to aid adherence.

Withdrawal from antiresorptive treatment is common due to adverse effects.303

Consider measuring bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) scanning after an interval of three years to assess response to treatment in postmenopausal women on alendronic acid, ibandronic acid, and zoledronic acid or denosumab therapy.109 Consider this on a case-by-case basis, where adherence with treatment is of concern.

When medicines should not be stopped

Continue antiresorptive treatment in those with a high risk of osteoporotic fragility fracture, including those aged over 75 years or with a previous hip or vertebral fracture.109^,308

Safety – specific medication safety issues to highlight

Bisphosphonate tablets should be swallowed whole with a full glass of water, on an empty stomach and it is important to remain upright (seated or standing) for at least 30 minutes after administration.212

Bisphosphonates are contra-indicated in the presence of hypocalcaemia, which should first be treated.212^,302

A dental check is advised before the person starts treatment. Those with poor dental status should be assessed by a dentist and have necessary remedial work performed prior to commencing bisphosphonate or denosumab therapy. After starting treatment, people should continue with good dental hygiene, receive routine dental check-ups and report any dental symptoms such as pain or swelling.109 The risk of osteonecrosis of the jaw is related to the potency of the bisphosphonate (highest for zoledronic acid), route of administration (IV highest), cumulative dose and duration.212

Atypical femoral fractures have been rarely reported with bisphosphonate and denosumab treatment.109^,212^,302 Individuals should report thigh, hip or groin pain and if these symptoms change, the femur should be imaged (by full-length femur X-ray, isotope scanning or MRI).302 The need to continue treatment should be re-evaluated periodically balancing risks against benefits.

Ear pain, discharge from the ear or an ear infection during bisphosphonate treatment should be reported. Benign idiopathic osteonecrosis of the external auditory canal has been reported very rarely.212

Risedronate should be used with caution if the person has delayed oesophageal emptying.¹⁰⁹

How and when to reduce and stop medication – deprescribing

1. People who stop taking regular or repeated courses of oral corticosteroids may be able to stop osteoporosis prevention treatment (reassess risk of osteoporotic fractures using online tools).²¹²

2. People taking bisphosphonates for osteoporosis, should have their fracture risk reassessed after three to five years, and women should continue treatment if they remain at high risk of fractures.300^,301

3. Low-to-moderate risk patients who are stable after five years of taking oral bisphosphonates or, after three years with intravenous zoledronic acid, may be considered for a ‘drug holiday’.299

4. Prescribers should be cautious about discontinuing alendronic acid, zoledronic acid or risedronate, because of the risk of bone mineral density reduction at the hip and lumbar spine, and because of the increased risk of vertebral fracture after discontinuation. However, some studies show that fracture risk after discontinuation of alendronic acid, zoledronic acid or risedronate in those who have had adherence rates of greater than or equal to 50% over three years, might be less than those who persist on therapy.307 Other risk factors such as advanced age, current smoking and a history of falls were predictive of BMD decrease or new fractures after discontinuation.307

5. Discontinuation of alendronic acid can change BMD at the femoral neck, total hip and distal third of the forearm after five years. However, after 10 years of follow-up, mean BMD remained at or above pre-treatment levels, whether treatment was continued or not.³⁰⁷

6. Discontinuation of zoledronic acid after three or six years does not make a difference to osteoporotic fractures.307

7. Because the benefits for bone remodelling with denosumab are reversed after six months, a ‘drug holiday’ is not suggested, therefore if stopping denosumab, to avoid a treatment gap, the person should receive other antiresorptive treatment to prevent rapid bone mineral density loss, increased fracture risk, or a rebound in bone turnover.300^,301^,302^,310 Those who have discontinued denosumab without seeking medical advice first should be referred urgently to the local Bone Health/Mineral Metabolism Clinic, including those who are over one month late for their six-monthly injection.

8. Zoledronic acid and risedronate are contra-indicated in severe renal impairment (eGFR ≤35ml/min and ≤30ml/min, respectively), whilst alendronic acid and ibandronic acid are cautioned against (eGFR ≤35ml/min and ≤30ml/min, respectively).109^,212

9. Those with severe renal impairment (eGFR 15-29ml/min) or receiving dialysis are at a greater risk of developing hypocalcaemia with denosumab and monitoring of calcium levels is recommended.²¹²

Supporting people who do not or cannot reduce/stop

Reinforce the advice regarding long-term safety and symptoms to report (dental pain, thigh, hip or groin pain and ear pain).

In women receiving bisphosphonate adjuvant therapy as part of breast cancer treatment, do not stop this treatment without first consulting their oncology team.

Specific areas/situations where medication may need to be introduced or increased

Individuals taking prednisolone 7.5mg daily for three months or more should be offered antiresorptive treatment. This includes those taking repeated short courses of prednisolone (three or more in 12 months).^109,212

If a fracture occurs whilst on bisphosphonate treatment, ask about adherence to treatment. If adherence is assured, then secondary causes for the fracture should be explored.³⁰²

If a new fracture occurs after bisphosphonate treatment is discontinued, the person should be reassessed.302

If no new fracture occurs after bisphosphonate discontinuation, the person should receive a fracture risk assessment at two-to-four-year intervals to determine if treatment should be restarted.300^,301

If BMD significantly declines, or if factors alter the person’s clinical risk; consider reinitiating therapy earlier.300^,301

Person-centredness – supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• Explain the risk of fractures without treatment and the benefits versus risk of commencing preventative osteoporosis treatment
• Oral bisphosphonates must be taken on an empty stomach as their absorption is affected by food, drink and other drugs. They must be taken with plain water 30 minutes before the first food, other medication or drink of the day. If this is not possible, then they should be taken at least two hours before or at least two hours after any food, other medication or drink (other than plain water). They must remain upright (seated or standing) for 30 minutes afterwards to reduce the likelihood of GI adverse effects^109,212
• Poor adherence with bisphosphonate therapy increases fracture risk
• Symptoms indicative of adverse effects (dental pain, thigh, hip or groin pain and ear pain)

Is drug therapy tailored to the individual?

• Increasing weight-bearing physical activity, stopping smoking and reducing alcohol intake are important lifestyle changes which will help to prevent osteoporosis and fragility fractures
• Highlight the importance of adherence to therapy in the absence of immediately obvious benefits.¹⁰⁹ Alternative formulations, such as once weekly formulations for bisphosphonates are available which may be helpful for adherence and are taken on the same day each week
• If a person has a multi-compartment compliance aid (MCA), the bisphosphonate should be packaged separately, in their original packaging, due to the special considerations required for taking the medication^[312]

Agree the plan

• Explain that if there are any new fractures, then the treatment plan will be reviewed
• Treatment will be reviewed on a regular basis to check that it is still appropriate
• If a carer is assisting with administration of medication, ensure they are aware of the advice regarding timing of administration

Decision support tools

• self-management/support tools
• decision aids

The Royal Osteoporosis Society produce information and support for people to help with bone health, including an osteoporosis risk checker.

There is a patient decision aid produced by NICE. Bisphosphonates for treating osteoporosis patient decision aid (nice.org.uk)

Decision support tools to assist in determination of risk of fracture are available:109

• FRAX tool
• Qfracture tool

Algorithms to assist in detection and management of osteoporosis are available. Figure 10 shows the algorithm from SIGN 142.¹⁰⁹ Local examples are also available in clinical handbooks.

Figure 10 reproduced from: Scottish Intercollegiate Guidelines Network (SIGN). Management of osteoporosis and the prevention of fragility fractures. Edinburgh: SIGN; 2021. (SIGN publication no.142). Figure available on the SIGN website.109

^* DEXA scan advisable to obtain baseline BMD but not necessary to initiate treatment; + One severe or two or more moderate vertebral fractures on x-ray, and T-score <-1.5 at any site or spine T score <-4.0

National Therapeutic Indicators for this hot topic

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Number of people prescribed a long-term oral steroid without co-prescription of a bone protecting agent as a percentage of all people prescribed a long-term oral steroid – see Chart 10

8.5.2 Hot Topic: Deprescribing in Palliative Care

What is the aim of this hot topic and therapy?

The aim of this hot topic is to promote active deprescribing of inappropriate medicines in individuals with a shortened life expectancy.

Palliative care is not limited to those with cancer and includes those living with and dying from any advanced, progressive incurable condition, for example end stage COPD, motor neurone disease, severe chronic heart failure. It focuses on addressing symptoms and helping people to live as well as possible until the end of their lives. The focus is on reducing medication burden and promoting person-centred discussions to enhance quality of life, adherence with essential medicines, and reduce the risk of adverse drug effects.^[313]

Is this an essential medicine?

For individuals with shortened life expectancy, there may be discrepancy between appropriateness of long-term medicines and their treatment goals. Consideration should be given to the length of time required to achieve the desired treatment outcomes and potential higher risk of adverse effects.

Important benefits and risks of treatment, including any groups where specific considerations are required

Polypharmacy is common in palliative care and individuals often have a high medication burden. Deprescribing of inappropriate medicines reduces the medication burden and promotes person-centred discussions to enhance quality of life.

Whilst many people welcome a reduction in medication burden, others may be concerned by it. It is important to acknowledge the fear and uncertainty that individuals and family/carers may experience when stopping a medication that they believe is necessary and that they had taken for chronic conditions.

Medication effectiveness - when should this be considered and why, i.e. efficacy, individual choice, side effects

Polypharmacy is common in palliative care. Individuals are often taking medicines for chronic conditions, in addition to treatments for symptom management. Medication reviews should be undertaken regularly to meet the changing needs of the individual, and to reduce potential harm from previously well tolerated medicines. Consider factors such as age, frailty, comorbidities, altered organ function and the number and types of medication taken. Deprescribing of medicines should be considered where appropriate.

After discussion and agreement with the individual and/or family/carers, any medicines that are not providing symptomatic benefit, are causing harm or are deemed no longer necessary should be stopped. This may include long-term prophylaxis medication such as statins and antihypertensives. ^[314]

The goal is to improve quality of life and reduce the burden of unnecessary treatments, particularly in the final months of life.

When medicines should not be stopped

Replacement therapies should be continued, e.g. levothyroxine, hydrocortisone, except under specialist advice. Insulin must be maintained in type 1 diabetes to prevent diabetic ketoacidosis, however a change to a simpler regimen such as once daily basal insulin can be considered.

Certain medications will need to be withdrawn more cautiously (e.g. cardiac rate control medications, immunosuppression in organ transplant recipients, antidepressants, opioids, benzodiazepines) to avoid withdrawal effects.

Safety – specific medication safety issues to highlight

The risks and benefits of each prescribed medication should be evaluated in the context of the individual’s overall health condition and the established goals of care. For example, the risk of continuing anticoagulation for atrial fibrillation needs to be balanced against the associated risk in malignancy that is prone to bleeding. There is often no right or wrong decision and an informed discussion with the individual and their family /caregivers should assess the risk and benefits.

The risk of aspiration associated with continuing medications when the oral route is compromised must be considered and evaluated. It may be possible to administer the medicine in an alternative form (e.g. patches) or via a different delivery route. It is common for medications to be administered by subcutaneous (SC) injection and by continuous subcutaneous infusion (CSCI) in palliative care. As most medication have no marketing authorisation for subcutaneous administration this constitutes off-label use.

The responsibility for prescribing under such circumstances lies with the prescriber, who should be able to justify and feel competent in using this medicine. The BNF provides guidance on prescribing in palliative care including the use of unlicensed or off-label medicines;314 further guidance on the prescribing unlicensed medicines is available from the General Medical Council. The Palliative Care Formulary also provides guidance on the prescribing of off-label and unlicensed medicines in palliative care. ^[315]

How and when to reduce and stop medication – deprescribing

Deprescribing should be considered proactively as part of ongoing clinical care, rather than as a separate reactive process as a consequence of an individual’s illness or development of an adverse drug reaction.^[316]

People nearing the end of life may be taking preventative medications for chronic illnesses, as well as others that are no longer appropriate. The change from curative to palliative therapy, with a focus on individual comfort, should translate into changes in prescribing.^[317]

It is appropriate to consider deprescribing in the following individuals:

• with malignant prognosis of six months or less as per OncPal guideline inclusion criteria.
• with chronic ill health who meet criteria outlined by the Supportive and Palliative Care Indicator Tool (SPICT), suggesting they are in the last 6-12 months of life.
• with a suspected prognosis of 6-12 months or less and Clinical Frailty Score 8-9, (based on expert opinion)

Specific areas/situations where medication may need to be introduced or increased

New medication may be required for the management of disease complications and the palliation of symptoms. These can be experienced as the disease progresses and an individual nears the end of life, for example, pain control, hypercalcaemia, nausea and vomiting.

The Scottish Palliative Care Guidelines provide practical, evidence-based or best-practice guidance on a range of common clinical issues for both generalist and specialist providers of palliative care.169

Person-centredness - supporting collaborative decision-making and understanding

Does the person understand the outcomes of the review, including risk and benefits?

• A person-centred approach is deemed to be an essential component of deprescribing decision-making.
• The priorities of individuals and their family/carers should be recognised and included as part of the deprescribing process.
• Care should be taken to ensure that the language used is aligned with shared expectations and shared decisions between the individual and prescriber.

Is drug therapy tailored to the individual?

Prescribing should be tailored to the needs of the individual with appropriate steps taken to:

• simply the medication regime
• continuing those medications that are essential
• consider withdrawing those that no longer provide benefit

Agree the plan

• Individuals and their family/carers should continue to be involved in decisions regarding medication and goals of care
• As death approaches, changes in care goals should be continuously and regularly evaluated, and appropriate changes to medication made.

Decision support tools

• self-management/support tools
• decision aids

The SPICT tool can be used to help identify people with deteriorating health due to a serious illness, one or more health conditions (multimorbidity) or frailty in older age so they benefit from holistic assessment, future care planning (advance/anticipatory care planning) and palliative care.

• Supportive and Palliative Care Indicators Tool (SPICT-4ALL™)

The following resources offer guidance on deprescribing in individuals with a shortened life expectancy.

• The OncPal Deprescribing guideline
• The ASSIGN Score –cardiovascular risk score
• Benzodiazepine tapering tool
• Prescribing Guidance for Moderate to Severely Frail Patients
• Guideline for deprescribing in patients with a shortened life expectancy across NHS Lanarkshire