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

Information and support for people starting a medicine

Evidence from study participants showed that they were often not given sufficient information about their medicine before starting treatment, particularly the risks of dependence and withdrawal symptoms. Participants also reported a lack of information about side effects, how well the medicine is expected to work, how long it will take to work and the likely duration of treatment. This evidence reflected the committee's experience. The recommendations aim to ensure that all of this information is provided before people begin treatment.

The committee also agreed that it is important to make people aware of how to safely store their medicines and included a cross reference to the NICE guideline on controlled drugs, which covers storage of medicines.

The evidence also showed discrepancies between the information people reported being given and the information their healthcare professionals reported giving them, highlighting the importance of providing both verbal and written information in the person's preferred format that they can take home for later reference.

There was no evidence on the views of family members or carers, so the committee made a recommendation for research on information for family members or carers.

Within the evidence, peer support (for example, through online forums) was identified as a valuable complement to information provided by healthcare professionals. The committee agreed with this finding and recommended that prescribers should consider supplementing information with details of peer support networks.

Management plan

Evidence and the committee's experience demonstrated the value of agreeing a management plan with the person. The plan should include practical information about the medicine, including how to take it safely, and set out when the medicine will be reviewed. The importance of giving a copy of the plan to the person was highlighted both in the evidence and the committee's experience.

The committee's experience and evidence from studies on opioids indicated that long-term treatment is a risk factor for dependence, and that higher doses taken long term increase this risk further. Therefore, the management plan should be reviewed regularly to ensure that the dosage remains optimal, the benefits of the medicine continue to outweigh the potential harms and the medicine is not continued when it is no longer needed.

Prescribing strategies

Although the evidence was limited, the committee agreed that there was some indication that starting a medicine at a low dose may reduce the risk of problems associated with dependence and the risk of withdrawal symptoms. This was supported by evidence in the risk factor review showing a dose–response association between higher doses of opioids and incident addiction to opioids when taken long term. Evidence and the committee's experience also showed that standard-release opioids are less frequently associated with problems compared with modified-release opioids unless clinical considerations or the person's circumstances dictate otherwise. The committee noted this only applied to opioid formulations and not to the other medicines considered.

The committee agreed, based on their experience, that it is important to take particular care during dose adjustments. Although pharmacological tolerance is a property of medicines described in this guideline, if a person has an initially favourable response that then diminishes, it is rarely helpful to increase the dose to try to restore the clinical benefit. This is because such an approach increases the risk of harmful prescribing, and also because the loss of benefit is rarely due to pharmacological tolerance, but due to other factors.

In the committee's experience, there may be individual circumstances in which adjustments are needed to the prescription to ensure it is safe and practical. If it is not possible for people to hold their own medicines, in secure settings for example, twice-daily administration may be difficult.

To avoid unnecessary long-term use of a medicine, prescribers should ensure that each prescription is in line with the management plan and complies with good practice guidance and relevant legislation.

Working with other healthcare professionals

The committee based these recommendations on their experience. They agreed that standardised prescribing practice can help to ensure continuity of care.

The committee's recommendations emphasise the importance of clear communication between primary and secondary care. They also stress the importance of giving clear explanations to people about arrangements for their care across services.

The committee agreed that it is vital that a new prescriber taking over a person's care acquires sufficient knowledge about the person to determine whether the prescription should be continued, establishes a therapeutic relationship with the person and takes the same care they would if they had been the original prescriber.

Primary and secondary care prescribers should ensure that they discuss and agree medicines to be prescribed or continued in primary care, and ensure that the person is kept involved and informed about these discussions. The committee noted that this is consistent with NHS England's guidance on responsibility for prescribing between primary and secondary/tertiary care (2018).

The committee recognised the difficulties involved in achieving and maintaining continuity of care and communication across settings, and agreed that it is helpful to have 1 prescriber take overall responsibility for a person's prescribing. It was noted that pharmacists may play an important role here.

Frequency of reviews

There was no evidence on the frequency of reviews, so the committee based the recommendations on their experience. They agreed that prescribing is an ongoing process that should be monitored with regular reviews. The frequency of these reviews should be tailored to the person, the medicine they are taking and the presence of any risk factors. They could be held by phone, video or face to face. The committee also agreed that the frequency of reviews could be increased during dose adjustments, to ensure safety and early identification of any withdrawal symptoms.

Content of reviews

Evidence and the committee's experience highlighted the importance of weighing up the benefits and risks of continuing or stopping the medicine as part of each review, and of updating the management plan after every review.

Making shared decisions about withdrawing medicines

The committee agreed that withdrawal should be considered when a medicine is no longer beneficial, the harms outweigh the benefits, or the person would like to withdraw. A small amount of evidence indicated that including the benefits of withdrawal and information about the process in discussions with the person can increase the likelihood that their withdrawal will be successful.

Qualitative evidence highlighted that people can be reluctant or anxious about discussing dependence and report feelings of fear, worry or anxiety surrounding discontinuation. The committee agreed that, in their experience, this can be addressed by explaining that dependence is an expected effect of the medicine, and some people experience problems associated with dependence. They also agreed it was important to avoid using language that ascribes blame to the person. The committee also thought it important to acknowledge and discuss differences of opinion and to be prepared for queries about the reasons for past prescribing.

Evidence from studies on benzodiazepines and antidepressants showed that a gradual, stepwise dose reduction is more beneficial than abrupt discontinuation. The committee agreed that this evidence can be extrapolated to opioids, Z‑drugs and gabapentinoids, and that none of these medicines should be stopped abruptly. However, the committee acknowledged clinical experience of exceptional circumstances in which stopping treatment abruptly might be necessary, for example if a serious side effect has occurred. In their experience, this would usually be done within a hospital setting.

Based on their experience, the committee agreed that individual factors can affect the withdrawal process and should be taken into account when planning withdrawal. The plan for withdrawal should also take into account the urgency of withdrawal.

Information and support for people withdrawing from a medicine

Based on both the qualitative evidence and their experience, the committee agreed that the provision of information and support is vital for people withdrawing from a medicine. Knowing what to expect, and having reassurance that they will have support and help with managing withdrawal symptoms, will increase the likelihood of a successful withdrawal. There was some qualitative evidence, reflected in the committee's experience, that support groups can be beneficial for people during the withdrawal process.

Dose reduction

The evidence comparing different speeds of dose reduction was inconclusive and the committee agreed that most of the studies did not reflect clinical practice. The committee are aware there are different terms used to describe reduction schedules. Based on their experience, they agreed that flexibility in schedules is needed, and tolerability is the most important factor to take into account when deciding the speed of dose reduction, and therefore a descriptive schedule incorporating these factors should be recommended. Although tolerability varies across individuals, most people find a stepwise, decremental dose reduction process tolerable and effective. With opioids, benzodiazepines, Z‑drugs and antidepressants, a rate of reduction proportionate to the existing dose is suggested. For gabapentinoids, the dose can be reduced by a fixed amount at each decrement, with the amount of reduction tailored to the person.

In the committee's experience, people who have some control over their own dose reduction schedule often have a more successful withdrawal than those whose schedule is decided for them. The committee also agreed that a flexible reduction schedule that is regularly reviewed and revised when needed is an important contributor to a successful outcome.

The committee noted that there was evidence for converting treatment from lorazepam to diazepam before withdrawal. This is because diazepam has a longer half‑life and is therefore considered to allow better management of the pace of reduction, and potentially reduce withdrawal symptoms. Withdrawing from a short-acting benzodiazepine such as lorazepam can be difficult because withdrawal symptoms can occur very quickly. The committee agreed that switching to a benzodiazepine with a longer half‑life is common practice and can be considered for people withdrawing from a benzodiazepine. Despite being common practice, there is a lack of evidence to support conversion to a preparation with a longer half‑life, so the committee made a recommendation for research on converting to a medicine with a different half-life to aid withdrawal. The committee agreed this recommendation for research should also apply to antidepressants.

Identifying and managing withdrawal symptoms

The committee recognised that it can be difficult to differentiate withdrawal symptoms from symptoms of a new or existing underlying condition. They agreed that withdrawal symptoms are often characterised by rapid onset after the dose of a medicine is reduced or the medicine is stopped, or there are qualitative differences from previous symptoms of the underlying illness, or there are new symptoms that have not previously occurred.

The committee agreed that if symptoms occur or worsen after a dose reduction, it is important to try to determine whether they are withdrawal symptoms or a re‑emergence of symptoms of the original condition. If they are likely to be withdrawal symptoms, the committee agreed that the next dose reduction may need to be delayed, or the person may need to revert to the previous dose.

The evidence did not inform of the frequency or prevalence of symptoms, and the committee agreed that withdrawal symptoms could vary widely between individuals in terms of which symptoms were experienced, but also in terms of their intensity and duration. The committee also agreed that, based on the current evidence, it would not be helpful to include a list of symptoms in the recommendation because this could be misleading and result in symptoms being overlooked if they are not on the list or wrongly implying new symptoms do not need further investigation.

Interventions to support withdrawal

There was little evidence on psychological interventions to support withdrawal or relieve withdrawal symptoms. Health economic analysis showed that group cognitive behavioural therapy (CBT) alongside dose reduction can improve discontinuation rates and quality of life for people during withdrawal from benzodiazepines and reduce costs for the NHS. There was no clear evidence on the most effective model or timing of CBT, so the committee also made a recommendation for research on CBT to support withdrawal from benzodiazepines. Evidence on other psychological interventions, or psychological interventions for other medicines, was too limited to inform recommendations, so the committee made a recommendation for research on psychological interventions to support withdrawal.

The committee agreed, based on their experience, that using another medicine associated with dependence and withdrawal symptoms to treat withdrawal symptoms does not aid withdrawal and can lead to harms.

The evidence did not support the use of pharmacological interventions to aid withdrawal, but was very limited for most pharmacological interventions. The committee agreed that sodium valproate and buspirone taken during withdrawal from a benzodiazepine are not only ineffective but are associated with harm and should not be used.

There was some evidence that a multicomponent intervention is beneficial during withdrawal from an opioid. However, the relative effectiveness of each component was not clear, so the committee made a recommendation for research on multicomponent withdrawal interventions.

Although acupuncture is commonly used in addiction services to manage dependence on illicit opioids, and there is some evidence supporting its use to aid withdrawal from opioids, evidence on its overall effectiveness is lacking. The committee made a recommendation for research on acupuncture to support withdrawal from opioids.

There was no evidence on the effectiveness of any withdrawal strategies or interventions to aid withdrawal from a gabapentinoid, so the committee made a recommendation for research on withdrawal interventions for gabapentinoids.

The committee were aware of specific equipment, practical aids and technologies used to support withdrawal but there was no evidence on these. They made a recommendation for research on aids to support withdrawal.

The committee discussed whether different service models, such as virtual clinics or specialist pharmacy input, would be effective in helping people withdraw from medicines. No evidence was identified in these areas and the committee made a recommendation for research on service models for withdrawal interventions.

Strategies if withdrawal cannot be agreed or is unsuccessful

The committee recognised that it may not be possible to reach a shared decision with the person about withdrawal and referred to the General Medical Council guidance for advice on how to handle this. They acknowledged particular difficulties if continued use of the medicine is especially hazardous, for example in a secure setting, and recommended steps that can be taken to manage withdrawal in this situation.

The committee recognised that dose reduction may sometimes be too difficult and agreed, based on their experience, that in this circumstance the aim should be to stop any further dose escalation and to make a plan to try again later. They stressed the importance of recording the reasons for continuing the medicine and the advice given to the person in the management plan.