The practical process of tapering gabapentinoids is broadly similar to that outlined previously for benzodiazepines and antidepressants. Readers are encouraged to read those sections. The main principles are briefly presented here.

• The indications for deprescribing are:

  • adverse effects,
  • lack of efficacy or loss of efficacy (tolerance),
  • the patient wishes to stop,
  • the condition treated has improved or alternative coping skills have been developed, and
  • rationalising medication (e.g. reducing polypharmacy).

• Patients at higher risk from continued use of gabapentinoids are:

  • those on concomitant use of opioids or benzodiazepines,
  • those diagnosed with COPD, severe or uncontrolled respiratory disease, or at risk of respiratory depression,
  • those who have a substance use disorder or a history of overdose, and
  • women who are pregnant or contemplating pregnancy. ¹
• Deprescribing decisions should be agreed between patient and prescriber. Forced tapers are not recommended.
• Life circumstances (e.g. burden of existing stressors and degree of social support available) should be taken into account when deciding when to commence tapering. A brief period of reflection and/or the mobilising of further resources may be required before commencing a taper.
• A key element of a deprescribing intervention is education regarding the risks, benefits and alternatives to gabapentinoids ² (see 'When and why to stop gabapentinoids').
• Patients should also be educated about the benefits, risks and alternatives to deprescribing (see 'Overview of gabapentinoid withdrawal effects').

• If deprescribing is declined: ³

  • patients should be advised of the relevant benefits of stopping,
  • any concerns they have about stopping should be addressed,
  • patients should not be pressurised,
  • if appropriate, readdress discontinuation at future appointments, and
  • continue monitoring for adverse effects.
• Note that some patients may be unable to withdraw completely, and a more suitable goal may be dose reduction or maintenance of the current dose.

• Patients should be warned not to stop gabapentinoids abruptly if they have been used for more than a few weeks. Explain that in some cases this can cause severe problems (e.g. rarely, seizures) ⁴ and might provoke long-lasting withdrawal symptoms.
• Reassurance may be required for those that have rapidly tapered in the past with intolerable consequences. Explain that if tapering is performed gradually and adjusted to their symptoms, it can be tolerable. Rapid withdrawal should be reserved for cases where the medication is causing severe acute harms.
• Preparation for gabapentinoid tapering may be required: for example, bolstering of existing coping skills or development of new ones. ⁵ These skills can include intentional relaxation (mindfulness, progressive muscle relaxation ⁶), controlled breathing exercises, ⁷ physical exercise (if tolerated), sleep hygiene, acceptance, distraction techniques, CBT for insomnia and stress reduction. ^{6, 8} There are a wide variety of other coping skills that people might find helpful. Lightening of work load or family duties may be useful, if this is possible.
• A support system should be established. ⁵ This can involve family and friends (who may require education) or more regular contact with clinical staff. Sometimes the introduction of patients to a supportive peer group in person or online can be vital to the process (although beware of exposure to 'worst-case' scenarios, and sometimes inaccurate information).
• Consider replacement treatment for the original condition. Specific treatments for the conditions for which gabapentinoids were originally prescribed (i.e. pain and anxiety) can be helpful for the process. However, there is also general recognition that gabapentinoids may not have marked long-term efficacy for a number of the conditions that they are used to treat.
• Manage expectations. For people that have used gabapentinoids long term, the withdrawal process can take months, or even longer for those sensitive to the process. ^{9, 10} People who have been on the drugs short term may be able to stop completely in a few weeks. ⁹
• Past experience of reducing can help predict symptoms that may arise again on tapering so should be noted and can be helpful for monitoring targeted symptoms (see below).
• Familiarity of the patient and the clinician with the wide variety of withdrawal symptoms ('Overview of gabapentinoid withdrawal effects') may help to mitigate unnecessary anxiety when symptoms arise. It should be impressed on patients that unpleasant withdrawal symptoms do not indicate that the drug is needed but that the taper rate should be slowed.

• It is thought that a patient-directed taper, adjusted to symptoms, is the most successful approach to cessation. ^{5, 9, 10} The key elements of a programme of tapering are:

  • that it is flexible and can be adjusted so that the process is tolerable for the patient;
  • that it involves close monitoring of withdrawal symptoms to facilitate timely adjustments to the rate of taper; and
  • that patients are provided with preparations of medication to enable the process of creating doses which cannot be made with widely available tablet or capsule doses (e.g. liquid formulations or smaller-dose formulations of tablets).

The process of tapering involves four steps (Figure 4.3 ).

Step one: estimation of risk of withdrawal and size of the initial dose reduction

Patients may be broadly risk stratified according to what little is known about risk of withdrawal ⁹ in the suggested approach below. It is better to err on the side of caution when estimating risk category and so the presence of any moderate or high-risk characteristic should assign a patient to that category. Tapers can always be sped up if no difficulties are encountered - but the reverse is not always true.

• Low-risk patients could start with approximately 25% (or less) dose reductions from the minimum clinically employed doses (or larger reductions from higher doses) - e.g. the faster regimens given in the drug-specific chapters. This group is characterised by:

  • no evidence of tolerance or inter-dose withdrawal,
  • short-term use ( weeks),
  • absent or only mild withdrawal symptoms on stopping or skipping a dose in the past, and
  • no history of multiple episodes of psychiatric medication use and cessation. ¹¹

• Moderate-risk patients could start with approximately 15% (or less) dose reductions from the minimum clinically employed doses (or larger reductions from higher doses) -e.g. the moderate regimens given in the drug-specific chapters. This group is characterised by:

  • some evidence of tolerance or inter-dose withdrawal,
  • moderate-length use (months),
  • moderate withdrawal symptoms in the past on stopping or skipping a dose, and
  • a history of some episodes of psychiatric medication use and cessation. ¹¹

• High-risk patients could start with 10% (or less) dose reduction from the minimum clinically employed doses (or larger reductions from higher doses) - e.g. the slower regimens given in the drug-specific chapters. This group is characterised by:

  • evidence of significant tolerance to the medication or marked experience of inter-dose withdrawal,
  • past history of severe withdrawal symptoms on dose reduction or skipping doses,
  • long-term use (years),
  • older or otherwise physically frail, and
  • repeated cycles of psychiatric use and cessation (which is thought to lead to sensitisation, a phenomenon sometimes called kindling). ¹¹
• In order to instil confidence in patients in what can be a daunting process, it may be advisable to start with an even smaller dose reduction in order to alleviate patients' fears and promote confidence about the process.
• None of these regimens should be imposed on the patient but are a starting point to assess how the patient tolerates the process. Some patients may require even slower tapers. ¹¹
• If a patient prefers to try a smaller dose reduction than their risk category suggests, this should be supported.

Step two: monitoring of withdrawal symptoms resulting from this initial reduction

• The most important information to determine the rate of reduction is how the patient experiences the process. Imposed regimens tend to backfire. ¹¹
• Although there are various scales used to measure withdrawal symptoms, these can be cumbersome because of the large number of items. Scales may also miss certain individual-specific symptoms and rarely rate the importance of symptoms to the patient. An alternative is to rate a small number of core withdrawal symptoms such as anxiety, insomnia, pain or other prominent symptoms characteristic for the individual out of 10 (0 = no symptoms, 10 = extreme symptoms) or to rate the withdrawal symptoms out of 10 overall. This monitoring often detects a 'wave' pattern of withdrawal symptoms: where symptoms increase, reach a peak, start to resolve and return to or approach baseline (Figure 4.4 ). See further variations of withdrawal symptoms in Figures 2.11-2.13.

The information from withdrawal monitoring can be used to determine the frequency and size of reductions. See further detailed examples in 'Recommendations for stopping antidepressants in clinical practice' but briefly:

• If symptoms take up to 2 weeks to resolve and the severity is mild (e.g. less than 4 out 10) then similar-sized reductions (in terms of receptor occupancy) could be made every 2-4 weeks.
• If symptoms take longer to resolve or their severity is moderate (e.g. 5-8 out of 10) then greater time between reductions will be required and/or smaller reductions made in future.
• If symptoms are severe (e.g. 9 or 10 out 10) then the dose should be increased to the last dose at which the patient was stable, and after stabilisation the rate of reduction should be halved, or slowed even further.

It is important, as already emphasised, that these decisions be reached jointly and that a too rapid rate of taper not be imposed on patients.

• The steps outlined above in steps 2 and 3 should be repeated. Similar-sized reductions (in terms of effect on target receptors) should produce similar withdrawal reactions, but sometimes these vary over time. Because of this variation, ongoing monitoring of withdrawal symptoms is warranted, with adjustment of the regimen according to the experience of the patient.

  • Reductions should proceed in a hyperbolic pattern to accommodate the nature of the pharmacological effect of the drugs such that reductions in dose become smaller and smaller as the total dose gets smaller. ^{12, 13} Examples of such regimens are displayed in the drug-specific sections of this chapter.
  • The taper should be flexible to accommodate periods of stress, increased responsibilities, illness or patient preference.
  • The dose should be reduced to zero only when the dose is low enough that the reduction to zero will not cause a larger change (in terms of effect on target receptors) than previous tolerable reductions have caused.

Some patients can have ongoing withdrawal symptoms following cessation. ^{14, 15, 16} Sometimes this lasts just for days or weeks but occasionally is extended for months or longer, termed protracted withdrawal syndrome - although it is not known how commonly these syndromes occur for gabapentinoids. ¹⁴ There are two main approaches to such problems - either supportive management or small-dose re-instatement. ¹¹ See section on management of protracted withdrawal for further details.

• Physical dependence and the experience of a withdrawal syndrome does not indicate addiction. ^{17, 18} Addiction centres are therefore not suitable for people suffering withdrawal effects from gabapentinoids without abuse or misuse. Sometimes treatment at these centres involves abrupt cessation with other medications added in to 'cover' withdrawal effects, or 12-step approaches inappropriate for medication taken as prescribed.
• Some symptoms can seem bizarre but should not be discounted as many are recognised as withdrawal symptoms (see 'Overview of gabapentinoid withdrawal effects') - e.g. myoclonus, depersonalisation/derealisation, strange tactile sensation, and vertigo. ^{14, 19, 20, 21}
• Symptoms of gabapentinoid withdrawal can overlap with the diagnostic criteria for other conditions, leading to misdiagnosis (e.g. functional neurological disorder, medically unexplained symptoms, psychosomatic conditions, chronic fatigue syndrome, anxiety disorders, depression, neurological disorders) and unnecessary testing and medical treatment. ¹¹
• Withdrawal symptoms are best managed by adjustment of the taper rate, rather than 'white-knuckling' through the process because it is thought that severe withdrawal effects may make a protracted withdrawal syndrome more likely and can sometimes be unbearable. ¹¹
• Adjunctive medication aimed at treating withdrawal symptoms has not been investigated, but it has shown limited success in tapering other dependence-forming medications ²² and NICE recommends that withdrawal symptoms not be treated with another medication that is associated with dependence or withdrawal symptoms. ⁹

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