Polypharmacy in Older People Part 2: A Guide for Healthcare Professionals

Overview

This is part 2 of our Guidelines summary on polypharmacy in older people. Recommendations covered in this summary are on the four-step approach and practical guide to stopping medication, including tapering information and withdrawal effects for nine classes of medication.

For recommendations on frailty, high-risk medication, sick day rules, reviewing patient medication adherence, the anticholinergic effect on cognition, and falls, refer to part 1 of this Guidelines summary.

For a complete set of recommendations, refer to the full guideline.

This summary as a whole has been reproduced with permission from the All Wales Medicines Strategy Group.

Reflecting on your Learnings

Reflection is important for continuous learning and development, and a critical part of the revalidation process for UK healthcare professionals. Click here to access the Guidelines Reflection Record. 

Four-Step Approach to Stopping Medication

1. Recognise the need to stop
2. Reduce or stop one medicine at a time
3. Consider if the medicine can be stopped abruptly or should be tapered
4. Assess risk benefit after each medicine has been stopped.

Recognise the Need to Stop

• A lot of medications are not required for lifelong use, and their need to continue should be reviewed frequently. Assessing whether the medication is still indicated and whether the risk outweighs the benefit should be part of this review
• When recognising medicines that may need to be stopped, utilise shared decision making with the patient and consider the patient’s and/or carer’s views on their medication.

Reduce or Stop One Medicine at a Time

• Reducing one medication at a time allows for identification of any issues that may occur as a result.

Consider if the Medication can be Stopped Abruptly or Should be Tapered

• Not all medication can be stopped abruptly as patients may develop withdrawal. It is important to taper some medication and monitor the patient’s response closely. If medication is being stopped due to toxicity, then the risk benefit should be assessed, and a more ambitious withdrawal may be undertaken
• Some medication may require close monitoring upon discontinuation and require tapering of doses. Specialist advice may be required to support the deprescribing of these medications:
  • antidepressants
  • antipsychotics
  • anticonvulsants
  • centrally-acting antihypertensives
  • corticosteroids
  • hypnotics and anxiolytics
  • opioid analgesics and gabapentinoids
  • anti-Parkinson’s.

Assess Risks and Benefits After Each Medication has Been Stopped

• Review if there has been any benefit to stopping or reducing the medication as an aid to continue deprescribing. If the patient has experienced re-emergence of the initial symptoms of treatment, then consider whether to restart the medication and whether the patient can benefit from a lower dose
• Resources such as the STOPP/START tool exist to help highlight medication for review in the older population. Further information on individual medicines can be accessed via www.medicines.org.uk or from the individual pharmaceutical companies’ medicines information departments.

The following sections aim to help support the deprescribing of some of the medications that require tapering regimens and close monitoring.

Antihypertensives

When to Consider Stopping

• Review if indication is still valid. Is blood pressure in range or too low?
• Is prescribing in line with national guidance?
• Is the patient exhibiting signs of postural hypotension? This is defined as a drop in blood pressure (BP)—usually >20/10 mmHg—within 3 minutes of standing
• Do adverse drug reactions outweigh possible benefits?
• Could the patient adopt lifestyle measures, such as losing weight, not misusing alcohol, exercising regularly, and restricting consumption of salt?
• Does the patient have general frailty? Consider if length of treatment time required for benefit outweighs the risks.

Tapering Guide

• Consider indication and other drug properties when reviewing antihypertensives before deciding which to reduce or withdraw, for example, rate-limiting properties of calcium channel blockers and cardioprotective properties of ACEis in heart failure
  • if more than one antihypertensive is used, stop one at a time maintaining the dose of the other antihypertensives
  • monitor the person closely; recurrence of hypertension is most likely to happen in the first 6 months
  • restart antihypertensives if BP increases above threshold stated in national guidelines.

Withdrawal Effect

• Withdrawal effects may be seen depending on drug and condition.^[A]

Benzodiazepines and Z-drugs

When to Consider Stopping

• Regular and prolonged use should be avoided as benzodiazepines and Z-drugs (for example, zopiclone and zolpidem) are associated with an increased risk of tolerance, falls, and cognitive impairment
• Patients should be prescribed the lowest possible dose for the shortest effective time. The maximum duration of treatment should be 4 weeks, including the tapering period
• Consider stopping if:
  • there is no documented indication
  • patient is palliative/end-of-life (bear in mind that benzodiazepines or Z-drugs may be of benefit to palliative patients)
  • benzodiazepines and Z-drugs are contraindicated, for example, myasthenia gravis
  • the risk of harm outweighs the benefits, for example, adverse drug reactions, patient is frail, or patient has multimorbidity
  • the patient is not experiencing the intended outcome or benefit
  • the duration of treatment is longer than the licensed recommendation.

Tapering Guide

• If benzodiazepines or Z-drugs have been taken for longer than 2 weeks, then there is a risk of withdrawal side effects and the withdrawal should be conducted gradually with frequent review
• Withdrawal should be done gradually in steps of around 5–10% reduction weekly to fortnightly, or one-eighth of the daily dose fortnightly
• Tapering down the dose of benzodiazepine or Z-drug can either be done on the person’s current medication or by switching to an equivalent dose of diazepam
• Switching benzodiazepine to equivalent diazepam dose is recommended for short-acting benzodiazepines, preparations that do not allow small dose reductions, and people who will likely experience difficulty withdrawing directly from temazepam, nitrazepam, and Z-drugs due to dependency
• Seek specialist advice before switching to diazepam in people with hepatic dysfunction
• When tapering with equivalent diazepam dose:
  • transfer the patient to equivalent daily dose of diazepam (see Table 1), preferably at night
  • reduce the dose of diazepam gradually every 2 weeks and if withdrawal symptoms occur, maintain this dose until symptoms improve
  • if necessary, reduce dose further in smaller steps depending on withdrawal symptoms
  • discontinuation can take 3–12 months and in some cases longer.

Table 1: Doses of Oral Benzodiazepines Equivalent to Oral Diazepam 5 mg

Withdrawal Effects^[A]

• Withdrawal effects may occur within 24 hours with short-acting benzodiazepines, or over several days with and longer-acting drugs
• Withdrawal effects may reach their maximum intensity between 3 and 14 days and can continue for up to 6 weeks
• Withdrawal symptoms are characterised by:
  • insomnia
  • anxiety
  • loss of appetite and of body weight
  • tremor
  • perspiration
  • tinnitus
  • perceptual disturbances
• Symptoms may be similar to original complaint and encourage further prescribing
• Some symptoms may continue for weeks after stopping benzodiazepines
• Seek advice from drug and alcohol services within your area. 

Oral Corticosteroids

Tapering Guide

• Be aware that too rapid a reduction of corticosteroid can lead to acute adrenal insufficiency, hypotension, and death
• Dose reduction should be done on a case-by-case basis considering the underlying condition being treated, the likelihood of relapse, and the duration of treatment
• Gradual withdrawal should be considered for people whose disease is unlikely to relapse and have one or more of the following:
  • received a dose of 40 mg of prednisolone daily or higher for more than 1 week
  • received repeated doses in the evening
  • received more than 3 weeks of treatment
  • recently received repeated courses; particularly if this has been for a period longer than 3 weeks
  • received a short course within 1 year of stopping long-term therapy
  • other possible causes of adrenal suppression
• During withdrawal, the dose of oral corticosteroids may be reduced rapidly down to physiological doses (approximately 7.5 mg prednisolone daily) and reduced more slowly thereafter
• If the problem has resolved and treatment has been given for only a few weeks reduce 2.5 mg equivalence prednisolone every 3–4 days to 7.5 mg daily, then more slowly by 2.5 mg weekly, fortnightly, or monthly
• If uncertain of disease resolution and/or therapy has been given for many weeks, reduce by 2.5 mg equivalence of prednisolone every fortnight or month down to 7.5 mg daily, then reduce by 1 mg every month
• If symptoms of disease are likely to recur on withdrawal, reduce by 1 mg every month.

Withdrawal Effects^[A]

• Too rapid a reduction of corticosteroid can lead to acute adrenal insufficiency, hypotension, and death
• Withdrawal symptoms include anorexia, hypotension, nausea, weakness, fever, myalgia, arthralgia, and weight loss.

Antidepressants

When to Consider Stopping

• Review if the indication is still valid:
  • for a single episode of depression treat for 6–9 months after remission of symptoms
  • for multiple episodes treat for at least 2 years after remission of symptoms
• Dosulepin should not routinely be prescribed
• Consider stopping:
  • in cases where there is no documented or appropriate clinical indication, supported by discussions with the patient and/or carer
  • when the known adverse drug reactions outweigh the possible benefits
  • if tricyclic antidepressants are being taken with other medications that increase the patient’s anticholinergic burden
  • if the patient is end-of-life and reduction in pill burden is required
  • if the patient has been treated at therapeutic dose for 6 weeks with no benefit. If partial benefit achieved, treatment duration may need extending or a dose increase should be considered.

Tapering Guide

• Due to the pharmacology of the drugs, doses of antidepressants should be tapered proportionately (for example, as a proportion of the previous dose), reducing by smaller and smaller amounts each time
• For people at a lower risk of withdrawal (for example, patients who have been prescribed only short-term antidepressants), tapering can be carried out in increments of 50% dose reductions made every 2–4 weeks down to a final dose of approximately 1% of original dose (see citalopram example in the Royal College of Psychiatrists guidance)
• Longer tapering regimes will be required for patients who:
  • develop distressing signs of withdrawal when trying to stop antidepressants
  • have been taking long-term antidepressants
  • have been taking antidepressants associated with a high risk of withdrawal effects (such as paroxetine, venlafaxine, and duloxetine)
• Such patients may need their doses reduced in increments of 10–25% of their previous dose every month, down to a final dose of approximately 1% of the original dose, or less. For patients at particularly high risk of withdrawal, increments of reduction may need to be as low as 5% of the previous dose every month (see paroxetine example in the Royal College of Psychiatrists guidance)
• Fluoxetine has a long half-life and active metabolites, making severe withdrawal less likely. However, as any withdrawal symptoms may develop several days or even weeks after reducing the dose, and as we cannot predict who will get symptoms, a 50% dose reduction made every 2–4 weeks down to a final dose of about 1% of original dose is recommended.

Refer to the full guideline for additional advice on the use of alternative formulations and 'every other day dosing'.

Withdrawal Effects^[A]

• Symptoms include dizziness, restlessness, problems sleeping, sweating, abdominal symptoms, nausea, changes in mood, akathisia, mania, and suicide ideation
• Withdrawal symptoms can start 24–72 hours after medication is reduced or stopped; for some people symptoms can start after missing a single dose
• See Table 2 for a list of individual antidepressants and their risk of withdrawal.

Table 2: Risk of Withdrawal Symptoms with Individual Antidepressants

• If an individual experiences mild discontinuation symptoms verbal reassurance to explain that most symptoms are short lived, along with safety netting advice, may be sufficient. Advise patients to seek help and contact a healthcare professional if their symptoms worsen
• More severe discontinuation symptoms may require re-starting the antidepressant at the previous dose, and attempting a slower reduction once symptoms have resolved. Withdrawal symptoms usually resolve quickly (in days or even hours) if the antidepressant is restarted.

Bisphosphonates

When to Consider Stopping

• Review treatment following deprescribing algorithm (see Algorithm 1)
• The risks and benefits of bisphosphonate treatment for the patient should be reviewed regularly. Consider whether the benefits justify the risks of bisphosphonate use, particularly in cases where:
  • the patient has an estimated glomerular filtration rate (eGFR) <35 ml/min
  • the patient is at a low risk of falls, for example are immobile
  • the patient is not able to sit upright to take oral bisphosphonate
  • the patient has developed swallowing issues
  • the patient is demonstrating poor adherence despite counselling
  • the patient has limited life expectancy or frailty
  • the patient has osteonecrosis of jaw or external auditory canal
  • the use of bisphosphonates is now contraindicated
• Some of the adverse drug reactions associated with bisphosphonate use include:
  • long-term use of bisphosphonates is associated with increased risk of atypical femoral fractures
  • intravenous bisphosphonates are associated with osteonecrosis of the jaw
  • long-term use of bisphosphonates has been associated with benign idiopathic osteonecrosis of the external auditory canal
• Emerging evidence suggests a possible link between the use of PPIs (especially high doses for over 1 year) and an increased risk of fracture. It may be prudent to ensure patients have a valid indication for a PPI and are prescribed the lowest dose for the shortest duration.

Withdrawal Effects^[A]

• Withdrawal of oral bisphosphonate treatment is associated with decrease in bone mineral density and increased bone turnover after:
  • 2–3 years for alendronic acid
  • 1–2 years for ibandronic acid and risedronate
• In the case of zoledronic acid, withdrawal after 3 years’ treatment is associated with only a very small decrease in bone mineral density after a further 3 years without treatment
• See Algorithm 1 for advice on reassessment.

Algorithm 1: Bisphosphonates Deprescribing Treatment

Acid Suppressants

When to Consider Stopping

• Proton pump inhibitors (PPIs) are associated with an increased risk of the following and should be reviewed if the patient is experiencing adverse effects:
  • infection including pneumonia and C. difficile
  • bone fractures
  • hyponatraemia
  • hypomagnesaemia
  • interstitial nephritis
  • vitamin b12 deficiency
• In addition, H2 receptor antagonists (H2RAs) are associated with a number of risks, including:
  • increased risk of C. difficile infection
  • the use of H2RA could potentially mask gastric cancer
  • the pharmacokinetics of certain drugs within this class (for example, cimetidine)
  • increase risk of drug–drug interactions
• Is indication still valid?
  • consider continuing in patients with a history of:
    • Barrett’s oesophagus
    • severe oesophagitis
    • history of bleeding ulcer
    • ongoing/uncontrolled gastro-oesophageal reflux disease (GORD)
  • consider continuing in patients co-prescribed potentially ulcerogenic medicine, for example, long-term steroids or nonsteroidal anti-inflammatory drugs NSAIDs
  • consider deprescribing in patients with:
    • mild-to-moderate GORD treated for more than 4–8 weeks (symptoms controlled)
    • peptic ulcer disease treated for 2–12 weeks (from NSAID use, H. pylori)
    • upper gastrointestinal symptoms without endoscopy, asymptomatic for 3 consecutive days
    • intensive care unit/surgery stress ulcer prophylaxis treated beyond a hospital admission
    • uncomplicated H. pylori treated for 2 weeks and now asymptomatic.

Tapering Guide

• Due to risk of rebound hypersecretion of gastric acid, tapering the dose of acid suppressant (PPI/H2RA) is recommended
• Review if PPI/H2RA can be stopped or stepped down:
  • step down: consider ‘as needed' PPI/H2RA treatment
  • stop: start gradual reduction with co-prescription of antacid and/or alginate for at least 2 weeks to reduce rebound hypersecretion
  • offer self-care advice.

Withdrawal Effects^[A]

• Monitor at 4 weeks and 12 weeks for heartburn, dyspepsia, regurgitation, epigastric pain, loss of appetite, or weight loss.

Opioids in Non-Cancer Pain

When to Consider Stopping

• Older patients and those who are frail, have low body weight, or renal/hepatic impairment, require reduced doses of opioids for non-cancer/palliative pain
• Tramadol is particularly hazardous in older people due to its increased half-life and increased risk of serotonin side effects and opioid side effects
• Transdermal opioids should be reserved for patients who are unable to receive oral medicines and should not be used for unstable pain until the efficacy of an opioid is established
• Oxycodone is associated with higher rates of misuse and dependence
• Modified-release opioids should be avoided until benefit has been demonstrated
• The maximum recommended dose of opioid morphine equivalent is 120 mg daily for chronic non-malignant pain. Doses above this should be considered for tapering and/or discontinuation as they are unlikely to provide benefit but may increase risk of adverse effects
• The effectiveness of medicines for chronic pain should be reviewed regularly and a periodic dose taper can help to confirm any benefits of treatment and assess the natural history of the pain
• The timing of a review is partly dependent on the presenting complaint and the agreed goals of treatment. For newly initiated treatment a review should take place within 2–4 weeks of initiation or dose changes. For patients on long-term therapy, a review should take place every 6 months
• Increased review should be prompted following concerns regarding efficacy of treatment or problematic use and for patients with an increased overdose risk or who have indicators of dependence
  • review diagnosis and type of pain, for example, neuropathic pain, non-responsive
  • review if indication still valid, for example, has patient had intervention such as joint replacement? Has underlying condition resolved?
  • has patient developed intolerable side effects?
  • review if pain is being managed; review if at least 30% pain reduction is not achieved
• Following initiation, if the patient doesn’t describe a benefit of opioid use in the first 2–4 weeks they are unlikely to benefit long term. If the patient still complains of pain despite opioid use, this is an indication that the opioid is ineffective, and they should be discontinued even if there are no other options. If a patient is not demonstrating benefit from a medicine, it should be carefully tapered and stopped.

Tapering Guide

• Opioids should not be stopped abruptly and should be tapered down gradually with regular review
• It is no longer best practice to consolidate all opioids a patient takes into a single, regularly prescribed modified-release preparation
• It is easier to taper opioids that the patient is familiar with
• ‘When required’ opioid prescriptions should not be used during tapering and opioids should be managed via acute prescriptions. It is important to ensure that the patient’s non-opioid pain management is optimised
• Extra caution should be taken when considering the use of NSAIDs in frail, older people due to renal and cardiovascular side effects. Therefore, they should be used at the smallest dose for the shortest period
• It is worth noting that the current evidence no longer supports the use for paracetamol in chronic pain conditions, and that a dose reduction my need to be considered in older patients with low body weight, low oral intake, or concurrent hepatotoxic medicine
• The dose of drug can be tapered by a maximum of 10% of the total daily dose weekly or 2-weekly but will depend on the individual’s response. Often this can be too big a dose reduction for many people and smaller dose reductions may be more successful. When making small dose adjustments it is worth noting what formulations are available. It may be beneficial changing to a different opioid formulation in order to make smaller reductions
• The rate and duration of taper should be adjusted to the patient’s response, and once the lowest dose is reached the time interval can be extended. 

Withdrawal Effects^[A]

• Stopping opioids suddenly can lead to withdrawal effects such as tiredness, diarrhoea, aching muscles, sweating, runny nose, and stomach cramps. Pain is also a withdrawal effect and can lead to patients remaining on opioids unnecessarily.

Gabapentinoids in Neuropathic Pain

When to Consider Stopping

• Gabapentin should be reviewed after 4–6 weeks to review benefit, as after this period the initial benefit for neuropathic pain may no longer occur
• If a patient has no response after 4 weeks of therapeutic medicines for neuropathic pain, they are unlikely to respond. Therefore, the medicine should be tapered and stopped
• Combinations of gabapentinoids with opioids and/or benzodiazepines can lead to accumulative side effects such as sedation and ventilator impairment; therefore, use of these combinations should be prioritised for review. Warnings have been issued regarding the risk of respiratory depression with gabapentinoids.

Tapering Guide

• Pregabalin: reduce the daily dose by 50 mg at each dose change. Dose changes may occur weekly, fortnightly, or monthly depending on an agreed reduction regimen with the patient
• Gabapentin: reduce the daily dose by 300 mg every dose change. Dose changes may occur weekly, fortnightly, or monthly depending on an agreed reduction regimen with the patient
• If a gabapentinoid must be discontinued for a medical reason this can be done gradually over a minimum period of 1 week for any indication.

Withdrawal Effects^[A]

• Patients may experience withdrawal effects from treatment cessation; therefore it is important to work closely with the patient to monitor their response
• Withdrawal symptoms include anxiety, insomnia, nausea, pain, and sweating.

Acetylcholine Esterase Inhibitors and Memantine in Dementia

When to Consider Stopping

• Consider stopping in the following:
  • significant cognitive decline over the past 6 months
  • no benefit of treatment
  • severe or end-stage dementia
  • refusal/inability to take medication that cannot be resolved
  • drug–drug, drug–disease interactions that make treatment a risk
  • severe agitation/restlessness
  • non-dementia terminal illness.

Tapering Guide

• It is recommended to slowly taper the dose and monitor response upon withdrawal of acetylcholine esterase inhibitors and memantine
• Review at 4 weeks (shorter follow up may be required in some patients)
• Continue in a stepwise approach until treatment is stopped
• In some cases where risk outweighs benefit, abruptly stopping medication may be necessary.

Treatment Breaks

• Treatment breaks may require re-titration of drug, contact a specialist to review. The regimens listed in Table 3 are a suggested guide only.

Table 3: Suggested Regimens for Treatment Breaks and Suggested Actions at the Point of Resuming Treatment

Antipsychotics to Treat Non-cognitive Symptoms of Dementia (Previously Known as Behavioural and Psychological Symptoms of Dementia)

For recommendations on antipsychotics to treat non-cognitive symptoms of dementia, refer to the full guideline.

Footnote

[A] For an accurate list of withdrawal effects for the medications listed in this summary, check individual drug summaries of product characteristics on medicines.org.uk.