A practical guide to stopping medicines in older people

Reviewing the treatment needs of an older patient who is taking multiple medicines can be a complex and time consuming task. It can be difficult to know which medicine, if any, to stop. In some circumstances, the only way to know whether or not to stop a medicine is to actually stop it and see what happens.⁴

One way of considering if any medicines are able to be stopped is to group them into two categories – those that improve day-to-day quality of life and those that prevent future illness (see Box below). Thinking about medicines in this way may provide a good starting point for talking with patients about the role and importance of each medicine. It may also allow a discussion about any variance between the goals of the doctor and those of the patient – the question is “what is the clinical and personal significance of this specific drug for this particular patient?”

An estimation of life expectancy may be difficult and needs to take into account not only the person’s age but also how many medical problems they have, how severe they are and how well they function.⁵ Diagnosis of a life-limiting illness may make the decision to stop long term medicines easier, but in reality, approaches range from stopping everything (except palliative medicine) to continuing all medicines until the patient is physically unable to take them.⁶

Best practice tip: Consider medicine regimens to have an expiry or “best before” date. Make sure that medicine reviews are carried out by this date unless there has been a change in the patient’s clinical condition that prompts an earlier review. Use your PMS to make sure that reviews are done at least annually for older people.

Factors to consider when deciding if a medicine can be stopped include:

• The wishes of the patient
• Clinical indication and benefit
• Appropriateness
• Duration of use
• Adherence
• The prescribing cascade

The wishes of the patient

The majority of people who take medicines would prefer not to, or at least to take only those that are really needed. Patients often ask if any of their pills can be stopped. It is easy to say “no” and continue on with the consultation but ideally this query should be viewed as a chance for a medicine review. Suggest a “brown bag review”, where the patient brings in all their medicine, including over-the-counter and complementary/herbal medicines and also those that they are not actually taking but are still in their cupboard. Consider involving the practice nurse and pharmacist for a team approach.

See BPJ 11 (Feb, 2008) “Principles of prescribing for elderly people” for more information on a “brown bag review”.

Clinical indication

Check that there is still a valid clinical indication and ongoing clinical benefit for each medicine. It may be necessary to review the patient notes to check what the original indication was. Consider if the benefit of the drug has already been achieved or if the clinical condition of the patient has changed.

Examples may include:

• A patient no longer taking a NSAID who now may not need a gastroprotective agent
• A patient with treated congestive heart failure who may be able to have their diuretic reduced or stopped
• A patient who has been successful with lifestyle modifications (such as a healthier diet, weight loss and smoking cessation) who may no longer require an antihypertensive
• A patient diagnosed with a terminal illness and a prognosis that makes the benefit of preventative medicines such as bisphosphonates and statins unlikely to be realised in that patient’s lifetime

Appropriateness

Check that the medicine is appropriate for use in an older person (see below). Two large studies have shown that approximately 21% of medicines used in older people may be inappropriate.^7,8 Some medicines are less safe for use in older people and more likely to cause adverse effects or have an increased risk of medicine interactions.

Examples of medicines that may be inappropriate in older people include:

• Amitriptyline (particularly doses > 50mg), which is likely to cause sedation and also has strong anticholinergic actions - nortriptyline is recommended as a safer alternative if a tricyclic is required.
• Benzodiazepines, which can cause excessive sedation and increase the risk of falls.
• Dextropropoxyphene, which can cause confusion and excessive sedation particularly in older people. Evidence shows that it is no more effective for pain than regular paracetamol use.⁹ Due to this unfavourable risk-benefit balance, dextropropoxyphene is being withdrawn from the New Zealand market on 1 August 2010.

See BPJ 26 (Mar, 2010) “Dextropropoxyphene containing medicines to be withdrawn”.

Consider if there are any other solutions that may be effective e.g. diet modification instead of a statin for reducing cholesterol, or non-pharmacological treatment instead of an antipsychotic for the behavioural and psychological symptoms of dementia.

Duration of use

Check how long the patient has been on the medicine. Some medicines are repeated for years as it can be quicker and simpler to maintain the status quo.

Check if there was a clear understanding at the time of initiation about the expected duration of use, particularly if the medicine was started in a secondary care setting. For example, a patient who was initiated on dipyridamole after a TIA, who has had no further ischaemic events, may be able to stop this medicine after two years.

Check whether there is still an indication for the use of the medicine and if so, that its use is still consistent with recommendations in current guidelines. Consider if there are more up-to-date drugs on the market that may be superior and safer.

Adherence

Check if the patient is taking all of their prescribed medicines. If not, ask them why? Did they understand the aims of treatment and did they experience any adverse effects? If the patient has remained well without the medicine, and is unlikely to suffer harm if it is not taken, consider stopping it e.g. corticosteroid inhalers for COPD.

The prescribing cascade

When a patient presents with new symptoms, consider an adverse medicine reaction as a possible cause. The aim is to avoid the prescribing cascade where additional medicines are initiated to treat adverse effects (both recognised and unrecognised) of other medicines.

Examples include:

• A patient taking 50 mg amitriptyline for pain presents with incontinence and/or constipation. Amitriptyline has anticholinergic actions which can cause urinary retention leading to overflow incontinence. If this is not recognised, oxybutynin may be prescribed, which aggravates the incontinence because it also has anticholinergic actions. In addition, the patient then becomes constipated and a laxative is prescribed. One medicine has led to the use of three others. Stopping the amitriptyline and finding an alternative medicine for the pain may be the best action
• A patient taking a calcium channel blocker presents with ankle swelling. Avoid prescribing a diuretic as they are not effective in this situation.
• For any patients taking NSAIDs who develop dyspepsia, hypertension or heart failure consider the NSAID as a potential cause.

Stopping medicines may result in one or more of the following outcomes:

1. No adverse consequence for the patient
2. Withdrawal events/symptoms that have a pharmacological or physiological basis, including rebound symptoms e.g. rebound hypertension after discontinuing therapy with a beta blocker
3. Signs or symptoms of the pre-existing disease may re-appear e.g. increased blood pressure after stopping an antihypertensive.

How a medicine is stopped is likely to alter the risk of withdrawal symptoms

For some classes of medicine e.g. beta-blockers, corticosteroids and antidepressants, abrupt withdrawal can induce morbidity and even mortality as a result of rebound phenomena and specific withdrawal syndromes.¹² For many medicines, tapering the dose is likely to be safer and better tolerated by the patient than abrupt discontinuation.

For example, abrupt discontinuation of:

• A beta-blocker may result in rebound tachycardia, an increase in blood pressure and, in some circumstances, cardiac ischaemia.
• An antidepressant may result in withdrawal symptoms that are similar to those of depression, which may make it difficult to determine whether the original depression has returned, or if the symptoms are a result of the abrupt discontinuation.
• A PPI is more likely to result in rebound hyperacidity.

Take a stepwise approach to stopping medicines

A four step process can be used when stopping medicines:¹³

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. Check for benefit or harm after each medicine has been stopped

Recognise the need to stop a medicine
When the patient presents for a renewal of medicine ask if they have any new symptoms (including adverse effects) or any concerns about their medicine. Has the clinical condition of the patient changed? Consider the preferences of the patient.

Are there drugs that can be stopped? If more than one medicine can be stopped, which one should be stopped first? This relies on clinical judgement and consideration of factors such as medicines most likely to cause adverse effects or without clear indications.

Reduce or stop one medicine at a time
Try to reduce or stop only one medicine at one time. If problems develop it is then easier to know what the likely cause may be.

Taper medicines when appropriate
To reduce the likelihood of an adverse withdrawal event, many medicines should be tapered. It can be difficult to determine which can just be stopped and which should be tapered. Therefore if in doubt taper, as it is safer. For many medicines the first step in tapering is to halve the dose. The dose should then be tapered in a stepwise manner to establish if the patient’s symptoms, conditions or risks can be managed with a lower dose or whether the medicine can be stopped completely.¹³

Generally there will be plenty of time to taper a medicine. If the medicine is being discontinued because toxicity is a concern, then a more ambitious taper can be undertaken or the medicine stopped abruptly. Once tapering has begun, ask the patient to note any symptoms that may suggest a more gradual withdrawal is required e.g. dyspepsia with reduced dose of PPI.

If intolerable symptoms occur following a decrease in the dose or after the medicine has been stopped, then it may be necessary to restart the previously prescribed dose and then try tapering again, but at a more gradual rate.

Check for benefit or harm after each medicine has been stopped
Ask the patient if any changes have occurred after a medicine has been stopped. Beneficial effects should be noted to reinforce that the decision to reduce or stop the medicine was correct. There is also evidence that the beneficial effects of some medicines may persist even after the medicine is stopped e.g. treatment with a bisphosphonate for five years, gives an ongoing reduction in risk of fracture for a further five years.¹⁴

If symptoms of the initial condition return and are troublesome, despite gradual tapering, then it may be that the medicine cannot be stopped completely. The patient may however be able to be managed on a reduced dose e.g. 10 mg PPI rather than 20 mg.

Antidepressants

Antidepressants should be tapered rather than stopped abruptly, to reduce the risk of developing a discontinuation syndrome and to allow time to assess the possible re-emergence of depressive symptoms (Table 1). Antidepressant discontinuation syndrome is more likely with a longer duration of treatment and a shorter half-life of the treatment drug.¹⁵

Antidepressants should normally be withdrawn over at least a four week period. Patients may experience withdrawal symptoms but usually these are mild and self-limiting. If these symptoms are not tolerated, it may be necessary to resume the previous dose and then reduce the antidepressant more slowly.¹⁶

Benzodiazepines

Regular and prolonged use of hypnotics should be avoided because of the risk of tolerance to effects, dependence and an increased risk of adverse events.^19,20

Patients who have taken benzodiazepines on a long term basis should be withdrawn gradually over a number of months (e.g. six months). The longer a patient has been taking a benzodiazepine, the more likely they are to develop dependence and tolerance.

There are a wide range of withdrawal symptoms (Table 2) and some may be similar to those for which the benzodiazepine was originally prescribed. Some patients may experience withdrawal symptoms such as rebound insomnia and anxiety after only two to four weeks of treatment. Withdrawal symptoms can continue for weeks or months after stopping a benzodiazepine.¹⁸ An awareness of this may help prevent additional medicines being prescribed for these symptoms.

Abrupt withdrawal may result in confusion, toxic psychosis, seizures or a condition termed benzodiazepine withdrawal syndrome which is similar to delirium tremens.¹⁸ Typical symptoms of this include insomnia, loss of appetite, weight loss, sweating, perspiration, tinnitus and disturbances of perception. Benzodiazepine withdrawal syndrome can occur within one day of stopping a short-acting benzodiazepine or up to three weeks after stopping a long-acting benzodiazepine.¹⁸

Successful discontinuation may result in improvements in cognitive and psychomotor function, particularly in older people. Patients may be more alert and have increased working memory, reaction times and balance.¹² Alternative strategies for insomnia (e.g. sleep compression, See BPJ 14) may be required as improvements may not occur for some months after the benzodiazepine has been stopped.²¹

Antihypertensives

Beta-blockers are the cardiovascular medicine most often associated with adverse withdrawal events. Abrupt withdrawal may cause rebound hypertension, tachycardia, arrhythmia or angina. These events may be physiological withdrawal reactions or an exacerbation of the underlying condition.¹³ Gradual dose reduction is required (Table 3).

Statins

The decision to stop a statin is based on an assessment of individual benefits and risks. For example, stopping may be justified in a person at relatively low risk of a cardiovascular event, who is also poorly compliant or experiencing troublesome adverse effects. In most cases statins can be stopped without the need for tapering.

Statins should not be stopped in patients admitted with (or with a history of ) cardiovascular events including acute coronary syndrome, myocardial infarction and stroke.

Warfarin

In older people taking warfarin, low initial and maintenance dosages are recommended (e.g. dose adjusted to maintain the INR at the lower end of the range of 2–3).²³ The optimum duration of warfarin therapy is determined by the condition being treated and its severity.²³

Some clinicians tail off long-term treatment over several weeks but the need for this is unclear. It is possible to stop abruptly rather than taper (Table 4).²⁴

NSAIDS

Consider stopping NSAID therapy when the risks associated with treatment outweigh the benefit. Risks associated with NSAIDs usually relate to declining renal function in the older age group and adverse gastrointestinal effects. NSAIDs may also reduce the effectiveness of antihypertensive therapy. Some patients may tolerate abrupt discontinuation but tapering the dose allows for other analgesics to be introduced or increased (Table 5).

Acid suppressants

Many people remain on acid suppressants despite there being no ongoing clinical indication e.g. NSAID stopped or H. pylori successfully treated. It is often possible to maintain symptom control on a lower dose or on an as needed basis rather than on long term high dose maintenance therapy.

Tapering the dose of an acid suppressant (both PPIs and H₂RAs) is recommended because of the risk of rebound hypersecretion of gastric acid (Table 6).²⁵ If rebound hyperacidity is mistaken for a return of the underlying condition then acid suppressants may be restarted unnecessarily. Following discontinuance of omeprazole therapy, gastric acid secretion returns to baseline over a three to five day period.²³

Bisphosphonates

The beneficial effects (e.g. prevention of bone loss, improved bone mineral density [BMD], and reduced risk of both vertebral and non-vertebral fractures) are seen within one year of starting treatment. Beneficial effects on BMD persist after stopping the drug.²⁶ The half-life of bisphosphonates appears to be very long (probably up to several years) because of skeletal storage.²⁷ This may explain continued effectiveness after discontinuation.

Alendronate can be stopped abruptly without the need for tapering.

For correspondence regarding stopping alendronate therapy, see "Correspondence: Guidance for stopping alendronate", BPJ 46 (September, 2012).

Oral Corticosteroids

Administration of oral corticosteroids for more than three weeks, or shorter courses at high doses (≥40mg prednisone), can lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis.

Tapering may not be required for some patients who have received low to moderate doses (e.g. <40mg prednisone) of corticosteroids for less than three weeks, however this will depend on the patient and the disease being treated.

Withdrawal should not be abrupt for the majority of patients who have been taking systemic corticosteroids for more than three weeks. These patients should generally have their corticosteroid slowly tapered to allow the HPA axis to recover (over weeks or months).^23,26 The rate of dose reduction will vary depending on the original dose and duration of treatment, the disease and the response of the patient.²⁶ If the disease flares up during withdrawal, the dose may need to be increased and the subsequent withdrawal to be more gradual. An increase in dose may also be required during periods of stress e.g. infection, trauma or surgery. There are several methods for tapering oral corticosteroids (Table 7).

Antiparkinson agents

The majority of patients respond initially to levodopa and its use improves the quality of life. After two years or more, benefit is reduced as the disease progresses and late complications emerge.²⁶ The long term use of levodopa is limited by motor complications and drug induced dyskinesias.

If antiparkinsonian drug therapy is reduced abruptly, or discontinued, a symptom complex resembling neuroleptic malignant syndrome can occur (Table 8).²³