Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults

Before starting treatment with an opioid, benzodiazepine, gabapentinoid, Z‑drug or antidepressant, give the person verbal and written information (in their preferred format) about the medicine. Ensure that the information is evidence-based and understandable by the person. Explain to the person:

• the potential side effects of the medicine, whether these are likely to be temporary or permanent and whether they might improve or worsen over time

• any additional implications of taking the medicine if the person is pregnant or planning pregnancy

• what the options might be if the medicine does not work

• how difficult it might be to stop the medicine later and how that might be managed (see the section on withdrawing a dependence-forming medicine or antidepressant)

• that missing doses may lead to symptoms of withdrawal

• how to store medicines safely (for more information, see the NICE guideline on controlled drugs).

Before starting treatment with an opioid, benzodiazepine, gabapentinoid or Z‑drug, explain and discuss with the person:

• that dependence is an expected effect of these medicines and is not a reason in itself to avoid the medicine

• the potential for developing problems associated with dependence

• the symptoms that suggest the development of problems associated with dependence and, if appropriate, the importance of making family members, carers or other people close to them aware of these symptoms.

Before starting treatment with an antidepressant or gabapentinoid, explain and discuss with the person:

• that any beneficial effect of the medicine may occur slowly, and they might experience side effects before noticing any benefit

• that many side effects are likely to ease over time.

Consider supplementing verbal and written information with details of peer support networks or online forums suitable for the person.

Discuss and agree a management plan with the person. Document the plan in the person's medical record and give them a copy in their preferred format. Include:

• what the medicine has been prescribed for, the intended outcomes of treatment and how these might be assessed

• the starting dose and intervals between dose adjustments or titrations

• who to contact if problems occur

• information about how long the medicine will take to work and how long they might be taking it for

• the duration of each prescription that will be issued

• the risks of taking more than the prescribed dose

• the symptoms and signs of an overdose and what they should do if this happens

• the plans for reviewing the medicine (including where and by whom this will be done) and the date of their next review.

Think about a strategy for regular reviews and include these in the management plan. Use regular reviews to:

• ensure that the benefits of the medicine continue to outweigh the potential harms

• check whether the dose needs to be adjusted and, if so, how to do this safely.

Take steps to reduce the risk of developing problems associated with dependence, for example starting at a low dose, and consider avoiding modified-release opioids. Explain the importance of these steps to the person.

Discuss with the person the range of doses likely to be safe and effective. Start with a low dose and agree frequent, regular reviews to ensure that timely adjustments can be made to test effectiveness, safety and acceptability and to find the lowest effective dose. Once an effective dose has been established, avoid automatically increasing the dose if the response is not sustained.

If the person's individual circumstances or the setting (for example, a secure setting) mean that usual prescribing practices are not suitable, adjust the prescription to ensure that:

• the medicine can be administered safely as part of the setting's routine

• the medicine does not pose a risk to the person or to others living in that setting.
  
  For more information, see the NICE guideline on physical health of people in prison.

The duration of each individual prescription:

• should reflect the management plan (see recommendation 1.3.5)

• should comply with best practice in controlled drugs prescribing

• must comply with relevant legislation (for more information, see the NICE guideline on controlled drugs).

When starting a prescription suggested by another healthcare professional, taking over a person's care, or deciding whether to continue a prescription made by another healthcare professional:

• take the same level of care you would take if you were starting the prescription

• follow the section on supporting people taking a dependence-forming medicine or antidepressant to help establish the new relationship

• ensure that you have sufficient knowledge of the person's health and preferences to determine whether continued prescribing is in their best interests or whether careful withdrawal (in discussion with the person) would be more beneficial for them.

Healthcare professionals in secondary care who recommend a dependence-forming medicine or antidepressant to be started or continued in primary care should explain to the person that:

• the medicine will be prescribed by their primary care team

• the primary care team will need to review the medicine

• if the primary care team declines to prescribe the medicine, or wishes to delay it, the secondary and primary care teams will discuss the medicine and involve the person in these discussions, explaining the reasons for any delay

• the secondary care team might not continue to manage and provide the medicine if this is agreed after discussions.

When transferring responsibility for prescribing from secondary to primary care, ensure that all relevant healthcare professionals have access to the management plan in the person's medical record.

If possible, ensure that 1 person has overall responsibility for a prescription. If the initial prescriber is unable to review the medicine, ensure there are arrangements for review by another healthcare professional and that effective communication, including sharing the person's records and management plan as needed, is in place to support this.

Pharmacists working in primary care may play a key role in supporting prescribing. See the section on medication review in the NICE guideline on medicines optimisation.

Offer regular reviews (by phone, video or face to face) to people taking an opioid, benzodiazepine, gabapentinoid, Z‑drug or antidepressant. Base the frequency of reviews on:

• the person's preferences and circumstances

• the type of medicine they are taking and the dose

• factors that might indicate a need for frequent reviews, for example if:

  • the person has additional care needs (such as people with a learning disability or cognitive impairment)

  • the person is taking the medicine for the first time

  • there are potential adverse effects or problems associated with dependence

  • the medicine is being used outside its licensed indications

  • there is potential for misuse of the medicine.
    
    For more information on antidepressants, see the NICE guidelines on depression in adults and depression in adults with a chronic physical health problem.

Consider increasing the frequency of reviews during dose adjustment. Take into account the person's clinical and support needs when agreeing review frequency.

Offer extra, unscheduled reviews when needed, for example if the person:

• reports adverse effects from the medicine

• becomes pregnant or is planning pregnancy

• has a change in their physical or mental health condition, or social circumstances

• starts taking medicines from a different prescriber

• requests a change in dose.

For guidance on reviewing medicines, see the section on medication review in the NICE guideline on medicines optimisation and the section on reviewing medicines in the NICE guideline on medicines adherence.

During the review, discuss with the person the benefits and risks of continuing the current dose, adjusting the dose or stopping the medicine. Base decisions on this discussion, taking into account, for example:

• the benefits or harms the person is experiencing from continuing the medicine

• any signs that the person is developing problems associated with dependence (such as running out of a medicine early, making frequent requests for dose increases or reporting loss of efficacy of a medicine that was previously working well)

• the person's preferences.

Agree and update the management plan with the person after each review, and give them a copy (see recommendation 1.3.5). Check that they know who to contact if they have problems or concerns.

Discuss withdrawing an opioid, benzodiazepine, gabapentinoid, Z‑drug or antidepressant with the person if:

• it is no longer benefiting the person

• problems associated with dependence have developed

• the condition for which the medicine was prescribed has resolved

• the harms of the medicine outweigh the benefits

• the person wants to stop taking the medicine.

Explain the benefits the person can expect from reducing the medicine and aim to reach agreement using a shared decision-making approach. Allow enough time to explore the person's circumstances and preferences.

Understand that the person might be reluctant or anxious about discussing problems associated with dependence. Reassure them that dependence is an expected effect of these medicines and that problems associated with dependence sometimes develop. Be sensitive to the use of terminology that may apportion blame to the person or be perceived adversely.

Acknowledge and discuss with the person any differences between their views and your own about the risks and benefits of the medicine.

Be prepared for queries about prescribing decisions made previously. Explain that our understanding of the balance of risks and benefits of a medicine can change over time. If sufficient clinical detail is available, discuss the possibility that past prescribing was done in the person's best interests using the knowledge available at the time.

Do not stop a medicine abruptly (complete cessation with immediate effect) unless there are exceptional medical circumstances, such as the occurrence of serious side effects (for example, upper gastrointestinal bleeding from an antidepressant, respiratory depression from an opioid or severe ataxia from a gabapentinoid). In these circumstances, consider:

• scheduling more frequent reviews

• short-term use of medicines to treat the physical symptoms of withdrawal (for example, abdominal cramps and diarrhoea during withdrawal of an opioid).

When planning withdrawal from an opioid, benzodiazepine, gabapentinoid, Z‑drug or antidepressant, take into account:

• the urgency of the withdrawal, for example gradual withdrawal of a medicine that is no longer effective or necessary, or more rapid withdrawal of a medicine that is causing significant harm (the speed of rapid withdrawal depends on the type of medicine and the person's circumstances, see recommendation 1.5.6)

• whether the initial goal should be complete withdrawal or, for people who find complete withdrawal too difficult, whether dose reduction with ongoing review is a more realistic initial aim

• which medicine to reduce first, if the person will be withdrawing from more than 1 medicine

• factors that might increase the person's risk of problems during withdrawal, including:

  • long duration of medicine use

  • high dose of medicine

  • history of withdrawal symptoms

  • history of problems associated with dependence

  • taking an antidepressant with a short half-life

• any concurrent medicines and how these might affect the person's response to withdrawal

• factors that might influence the timing of the start of the dose reduction, such as the person's circumstances and available support.

Before starting withdrawal:

• give the person information about the process of withdrawal that is tailored to their situation and the medicine they are taking

• explain how the withdrawal will be carried out

• consider providing details of sources of peer support, national and local support groups for people who are withdrawing from a medicine.

Discuss withdrawal symptoms with the person and tell them about the support that is available. When discussing withdrawal symptoms, explain that:

• withdrawal can be difficult, and may take several months or more

• support will be available throughout the withdrawal process

• withdrawal symptoms do not affect everyone, and 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

• there are options for managing withdrawal symptoms (see the section on identifying and managing withdrawal symptoms and the section on interventions to support withdrawal)

• some people may experience withdrawal symptoms that can be difficult to distinguish from a re‑emergence of their original symptoms or a new disorder, and it is important to discuss these with a healthcare professional if they occur (see recommendation 1.5.17).

When agreeing a dose reduction schedule with the person:

• explain the risk of abrupt discontinuation and that the rate of safe withdrawal varies between people and can vary over time for the same person

• balance the risk of adverse events from continued exposure to the medicine with minimising the risk of withdrawal symptoms by slow dose reduction and withdrawal

• ensure that the planned rate of reduction is acceptable to the person

• explain that although withdrawal symptoms are to be expected, the reduction schedule can be modified to allow intolerable withdrawal symptoms to improve before making the next reduction

• consider giving the person additional control over the process of dose reduction (for example, by issuing their usual daily dose in a form that allows them to reduce the amount in small decrements at a pace of their choosing, rather than issuing successive prescriptions for reduced daily doses)

• agree regular intervals for reviewing and adjusting the reduction schedule as needed

• ensure the person knows who to contact if problems occur.

If the person is withdrawing from an opioid, benzodiazepine, Z‑drug or antidepressant, suggest a slow, stepwise rate of reduction proportionate to the existing dose, so that decrements become smaller as the dose is lowered, unless clinical risk is such that rapid withdrawal is needed (see recommendation 1.5.6).

If the person is withdrawing from a gabapentinoid, reduce the dose by a fixed amount at each decrement, unless clinical risk is such that rapid withdrawal is needed (see recommendation 1.5.6).

If the person is withdrawing from a benzodiazepine with a short half-life, consider switching to a benzodiazepine with a longer half-life.

If using a published withdrawal schedule, apply it flexibly to accommodate the person's preferences, changes to their circumstances and the response to dose reductions.

During withdrawal, offer continued management of the underlying condition for which the medicine was prescribed, if needed.

Ensure the plan for dose reduction or withdrawal is clearly recorded in the overall management plan.

Be aware that it can be difficult to distinguish between the re‑emergence of underlying conditions and the emergence of withdrawal symptoms. The following may indicate withdrawal symptoms rather than symptoms of an underlying condition:

• rapid or early onset of symptoms after a dose reduction or cessation of the medicine

• symptoms of the underlying illness that the person reports as qualitatively different or more intense than before

• new symptoms that the person has not experienced before.

Follow recommendation 1.2.8 for people who find it difficult to communicate their symptoms, for example people with a learning disability or cognitive impairment.

Use clinical judgement to determine the need for further investigation to rule out new pathology.

If distressing symptoms occur or worsen after a dose reduction:

• determine whether they are withdrawal symptoms or a re‑emergence of symptoms that were relieved by the medicine

• if the symptoms are new, think about delaying the next dose reduction, trying a smaller dose reduction or reverting to the previous dose.

Do not treat withdrawal symptoms with another medicine that is associated with dependence or withdrawal symptoms.

Do not offer sodium valproate or buspirone to aid withdrawal from a benzodiazepine.

Consider group cognitive behavioural therapy (CBT) when withdrawing from a benzodiazepine. Discuss the timing of referral for CBT with the person.

Follow recommendation 1.2.7 if a shared decision to withdraw cannot be reached and continuing the current prescription is not in the person's best interests. Be aware that medicines associated with dependence and withdrawal symptoms should not be stopped abruptly in most cases (see recommendation 1.5.6) and need to be reduced in line with the section on withdrawing medicines.

If continued use of the medicine may be particularly harmful for the person or others (for example, in a secure setting) and a dose reduction, or a more rapid reduction than the person wishes, is the safest option, consider:

• scheduling more frequent reviews

• short-term use of medicines to treat the physical symptoms of withdrawal (for example, abdominal cramps and diarrhoea during withdrawal of an opioid).

If dose reduction has been unsuccessful (for example because of intolerable withdrawal symptoms or a change in the person's physical, mental or social circumstances) and the current prescription needs to be continued:

• aim to stop any further escalation in dose

• make a plan to attempt dose reduction again at a later date

• clearly record the advice given to the person about the potential harms of continuing the medicine, and the reasons for continuing without a reduction, in the management plan.