Manage Medicines Associated with Dependence Carefully

Vishal Mashru Discusses Medicines Associated with Dependence and Withdrawal Symptoms, Exploring NICE’s Recommendations on Initiation, Review, and Cessation

Certain medications used regularly in clinical practice are known to be associated with dependence and withdrawal symptoms. The primary examples considered to be dependence forming are benzodiazepines, Z-drugs (such as zopiclone or zolpidem), opioids, gabapentin, and pregabalin.¹ Although historically not classified as associated with dependence, antidepressants—the prescribing of which has risen in recent years^2,3—are increasingly considered part of this group because they are associated with withdrawal symptoms upon cessation.¹ 

Because GPs are often the first point of contact with the health system, most prescribing of these medicines is initiated in primary care. For example, 1,912,443 items of opioid analgesics and 7,281,195 items of antidepressant medication were prescribed in GP practices in NHS England in November 2022.^2,4 

In addition to their potential for causing dependence and unpleasant withdrawal symptoms, some of these drugs carry further risks when used concomitantly with other medicines, especially opioids, benzodiazepines, and gabapentinoids; the Medicines and Healthcare products Regulatory Agency has highlighted the significance of these risks in a number of drug safety updates, notably concerning severe respiratory depression.^5–7

All of these medicines can have significant benefits for patients. These groups of medicines are used for many different indications, including chronic pain, epilepsy, depression, sleep disturbances, and anxiety—conditions that are generally quite complex and difficult to treat.^1,8 Often, it has taken patients many years to achieve effective management of their condition or symptoms, which makes them reluctant to address any potential dependence or withdrawal issues.¹ Patients with depression, for example, may have exhausted all other options before a specific antidepressant helped to provide symptom and mood control. For some particularly complex cases, these medications may even have been initiated following review by specialists (such as in neurology or pain management) when all other medication options have been exhausted. It is worth noting that these medications can also be prescribed on a short-term basis, for indications such as acute pain or insomnia related to bereavement.^1,9,10

These medications are likely to improve a patient’s quality of life and help them to participate in daily activities such as work, family life, supporting others, hobbies, and exercise. It is therefore understandable that the prescribing and deprescribing of these medicines is a complex area for clinicians to navigate, requiring considerable thought, discussion, and understanding. In this article, I discuss these medicines in relation to primary care, with a focus on NICE Guideline 215 (NG215), Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults.¹ 

The Difference Between Dependence and Addiction

Dependence and addiction are terms that are often used interchangeably, but it is important to note that they are not the same thing. Dependence is defined by the physical effects of a drug—in particular, the presence of withdrawal-type symptoms when a person stops taking the drug.^11,12 Addiction, on the other hand, is a diagnosable condition characterised by an individual’s compulsive use of drugs despite knowing the potential risks and consequences, and is associated with an unhealthy reliance on something, in this case a drug, as well as chemical changes in the brain and body.^1,11,12

NHS Ambitions for Reducing Prescribing and Improving Medicines Safety

The Medicines Safety Improvement Programme

Launched in July 2019 and updated in February 2021, NHS England’s Medicines Safety Improvement Programme (MedSIP), which ‘oversees quality improvement work in several key medication safety areas’, is an indication of the importance being placed on reducing the use of potentially harmful medicines.¹³ One of the key ambitions of the programme is to reduce severe harm from opioid medicines, in particular by reducing high-dose prescribing (greater than 120 mg of oral morphine equivalent) for noncancer pain by 50% by 2024.^14,15 MedSIP emphasises the importance of preventing unnecessary initiation, de-escalating current use, identifying patients at risk of chronic use, and supporting deprescribing where possible.¹⁵ The programme also involves quality-improvement work in other areas related to medicine safety, including anticoagulant prescribing, polypharmacy, and administration in care homes.^13,14

Primary Care Networks: Network Contract Directed Enhanced Service 2022–2023

The emphasis on addressing these medicines is even more apparent in the Primary Care Network (PCN) Directed Enhanced Service (DES) contract for 2022–2023.¹⁶ Within the PCN DES contract is a section on structured medication reviews (SMRs) and medicines optimisation, in which indicator SMR-01C relates to the review of patients using potentially addictive medicines.¹⁶ The patients in this priority cohort are outlined in Box 1.¹⁶

In the rationale for this specification, it is stressed that PCNs and practices should be reviewing these patient cohorts through shared decision-making conversations with the aim of ensuring the safety and success of their medication,¹⁶ and with a view to appropriate deprescribing and reducing patients’ doses in line with symptom control.

Reviews of Medicine Prescribing

In 2017, a review into prescribing and causes of dependence in England was commissioned through Public Health England (PHE).¹⁷ The focus of this review was on the medicines associated with dependence and withdrawal symptoms already outlined.¹⁷ The review and its analysis showed that, during a 12-month period between 2017 and 2018, 26% of adults in England had received prescriptions for at least one of these medications.¹⁷ The majority of these prescriptions were in the antidepressant and opioid categories, with 7.3 million and 5.6 million of the 11.5 million total recipients receiving antidepressants or opioid pain medicines, respectively.⁸ 

A further review into prescribing in the NHS (particularly overprescribing) was commissioned in 2018 by the then Secretary of State for Health and Social Care and led by Dr Keith Ridge, Chief Pharmaceutical Officer for England.¹⁸ Published in 2021, the report outlines that the prescribing of medicines is a complex process involving many different individuals during a patient’s journey, but that—through effective use of medicines—clinicians can achieve the best outcomes for patients, avoid waste, and ensure a sustainable NHS.¹⁸ These goals can be achieved through an increase in shared decision-making discussions with patients, nonmedicine-related interventions, and effective SMRs for patients on long-term medications.¹⁸

NICE Guideline 215

In light of this, the publication of NICE guidance on medicines associated with dependence or withdrawal symptoms is an important development—indeed, one of the key recommendations from the 2017 PHE review concerned enhancing clinical guidance in this area, with reference to this guideline, by then in development.^1,8 In NG215, NICE has provided principles for how the key medicines associated with dependence or withdrawal symptoms should be prescribed and, importantly, how they should be deprescribed.¹ Throughout the guideline, there is recognition that, although all of these medicines have a place in therapy, they are also associated with long-term effects, dependence, and addiction, so they should be prescribed with care.¹ It is important that, when considering these drugs, the risks and benefits for each patient are assessed.¹ Their association with dependence alone should not be a reason to avoid them.¹

The guidance covers five areas related to these medicines, namely:¹

• supporting people taking them
• making decisions about prescribing them
• initiating them
• reviewing them
• deprescribing them.

There will be different interpretations of how this guideline’s recommendations should be implemented within a primary care setting, but the overarching emphasis is on actively involving patients and carers in informed decision making at all stages of the process.¹ It can be helpful to adopt a practice-wide approach to managing these patients and medicines, such as by creating a dependence-forming medicines register, and to utilise other services to support the patient with condition management.

Considering a Dependence-Forming Medicine or Antidepressant

When considering any of these medicines and their associated risks, medical history is a key area to assess. Clinicians should consider the individual clinical situation, taking particular note of whether the person has a clear diagnosis supporting the prescription, as well as any mental-health-related issues or drug or alcohol misuse.¹ Once these have been considered, caution should also be exercised concerning any other medications that the patient is currently taking that could increase the risk, such as opioids being taken together with a benzodiazepine.¹

The evidence-based risks and benefits of these medicines should be discussed and explained at the very outset with patients, in a format that suits them, and clinicians should acknowledge and explain that these medicines are associated with dependence in some patients.¹ In addition, clinicians should consider whether other interventions—including nonpharmacological approaches and watchful waiting—could be more effective, and these options should be discussed with the person and offered.¹ Nonpharmacological approaches may include:

• social prescribing
• health and wellbeing coaching
• talking therapies
• physiotherapy
• exercise referral.

Starting a Dependence-Forming Medicine or Antidepressant

Once the decision has been made that prescribing one of these medicines would be an appropriate measure, a clinician must give due consideration to which medicine is chosen and at what dosage, and provide the patient with all the necessary, relevant information to help them understand the suggested treatment.¹ Importantly, clinicians must provide verbal and written information about and explain:¹

• what side effects the person may experience, how they could change over time, and whether they will likely be temporary or permanent
• any additional implications of the medicine if the person is pregnant or planning pregnancy
• that the medicine is associated with long-term dependence, with further explanation of how difficult it can be to stop the medicine, how withdrawal would likely be managed, and that missing doses may lead to symptoms of withdrawal
• what the next steps will be regarding this medicine—this would include giving details about the starting dose, intervals between dose adjustments, the durations of prescriptions, and the intended plan for review
• information about how the medicine works, including what its intended outcomes are and how these are assessed, how long it takes to work, how long they may be taking it for, and the risks, symptoms, and signs associated with overdose
• how to store the medicine safely
• who to contact if problems should occur relating to the medicine
• what options the person will have should the medication not work. 

The value of a strong, documented management plan—giving clear instructions to patients, but also to other healthcare professionals involved in their care—cannot be underestimated. A review period is a particularly important part of such a plan. Figure 1, from NG215, is a useful aid for clinicians considering starting a patient on any medicine associated with dependence or withdrawal symptoms, and details the essential information to provide to the patient and include in their management plan.^1,19 This plan should be given to the patient and included in their notes.¹

Figure 1: Recommended Actions Before Starting Medicines Associated with Dependence or Withdrawal Symptoms^1,19

Reviewing Patients Taking These Medicines

The key to good management of patients taking these medicines is regular review, and NICE underlines how critical this is, particularly when trying to prevent dependence.¹ Reviews can be undertaken using a variety of methods, including face-to-face, telephone, and video consultations, and they should be tailored to ensure the maximum benefit to the patient.¹ The frequency of review can vary from patient to patient, depending on individual circumstances—such as the type of medicine the patient is taking, the person’s individual care needs, and whether the medicine is being used off licence—as well as what stage of treatment they are on (for patients being initiated on or stopping these medicines, more frequent reviews and follow up may be appropriate).¹ NICE recommends that a person's management plan should be agreed with them and updated after each review and a copy given to them, with details of who to contact in case of problems or concerns.¹ Figure 2 is a tool produced alongside NG215, which may prove invaluable when reviewing patients taking medicines of this nature.^1,20 In addition, primary care clinicians may benefit from using clinical system templates, as they can help clinicians to capture all of the relevant information and ensure that each conversation is both thorough and properly documented.

Figure 2: Recommendations Actions When Reviewing Medicines Associated with Dependence or Withdrawal Symptoms^1,20

Deprescribing of Dependence-Forming Medications and Antidepressants

The deprescribing of these medicines is possibly the most challenging part of the review and management process, especially for patients who have become dependent or have been taking these medicines for a long time. Successful deprescribing relies on a clinician reassuring the patient and providing consistent and regular follow up to support them through this transition.¹ In practice, this process will vary from patient to patient—some may need weekly follow up, others only monthly. 

Deprescribing of these medicines should be considered and discussed at each medicines review as a minimum, but may be initiated outside of these regular reviews if prompted by a patient or healthcare professional.¹ Deprescribing can be appropriate for a variety of reasons, including:¹

• the medicine no longer providing any benefits, or the original condition being resolved
• the patient developing problems associated with dependence on the medicine
• benefits of the medicine no longer outweighing harms
• the patient deciding to initiate withdrawal. 

It may also be necessary to hold an initial discussion about deprescribing, outline a plan with the patient, and allow them time to consider their options before making any decisions.¹ This delay often allows the patient to make an informed choice, which is key to the shared decision-making process.²¹

It is important to explain to a patient how deprescribing will be carried out and give them some kind of timescale as a guide, but clinicians should be mindful that these timescales can change and are not rigid.¹ Plans must allow some flexibility, as they may require adaptation once deprescribing starts, and any dose-reduction schedule should be explained to and accepted by the person before it is initiated.¹ The clinician should give the patient tailored information about the process of withdrawal and how it will be carried out, and ensure that details of this are clearly recorded in the management plan.¹ When needed, a clinician can write the plan down for the patient, or ask them to write it down themselves, as this will likely help the patient to understand the plan and adhere to it.

Withdrawal Symptoms

It may be difficult to distinguish between withdrawal symptoms and re-emergence of an underlying condition; however, it is worth bearing in mind that withdrawal symptoms are usually associated with a rapid or early onset after medication reduction, and tend to be new upon deprescribing of the medicine or qualitatively different from pre-existing symptoms.¹ If a person reports distressing symptoms, particularly after a dose reduction, clinicians should use their judgement to consider whether further investigation is necessary, and whether the deprescribing plan should be adapted to ameliorate the person’s distress.¹ NICE recommends considering cognitive behavioural therapy for people undergoing dose reduction of a benzodiazepine, but does not recommend other interventions to support deprescribing, in particular advising against treating withdrawal symptoms with an alternative dependence-forming medicine, or using sodium valproate or buspirone to support deprescribing a benzodiazepine.¹

If dose reduction is unsuccessful, for example because the person’s withdrawal symptoms are intolerable, then NICE recommends continuing with the current prescription but avoiding any further escalation in dose, while also making plans with the person to try dose reduction again at a later date.¹ All such discussions and decisions should be recorded in the person’s management plan.¹

Useful Resources

There are many resources now available to support healthcare professionals and patients looking to deprescribe these medicines safely, and it is stressed in NG215 that clinicians should consider providing information about sources of support when deprescribing one of these medicines.¹ The resources listed in Box 2 are by no means the only ones available for healthcare professionals and patients, but I have used them in my own clinical practice. 

Summary

The prescribing and deprescribing of medicines associated with dependence or withdrawal is a complex area of practice that requires a lot of assessment and consideration, and it is important to have upfront and honest conversations with patients during the initiation, review, and deprescribing processes. Including patients in decision making is a key aspect of achieving success, and effective use of available guidance and resources will support both patients and healthcare professionals to achieve positive outcomes for everyone involved.