Many guidelines recommend deprescribing benzodiazepines and z-drugs in most long-term users. Due to physical dependence in those using medication as prescribed (distinct from addiction), discontinuation can be difficult and is often unsuccessful, as withdrawal symptoms can be severe and long-lasting, especially after long-term use. There is a lack of clarity on how to taper patients in a tolerable manner that minimizes discomfort. Current guidelines vary with some suggesting linear reductions (e.g. 1 mg every 1-4 weeks) and some proportionate reductions (e.g. 5%-10% of the most recent dose per month, with smaller reductions as the dose decreases). The shape of the relationship between dose of benzodiazepine and activity at gamma-aminobutyric acid-A (GABA-A) receptors is hyperbolic: steeply inclining at low doses, flattening at higher doses. Consequently, linear dose reductions produce increasingly large changes in receptor occupancy, predicting escalating withdrawal effects, while hyperbolic or proportionate dose reductions produce linear reductions in pharmacological effect. Slower tapering (over months and years) may be more successful than tapering over days or weeks. In practice, rate of tapering should be adjusted according to severity of withdrawal effects. Final doses for some people will need to be very small (equivalent to as little as 0.2 mg of diazepam, or less) so that the last 'step down' to zero is not larger than prior tolerated reductions in terms of pharmacological effects. Liquids or compounded formulations of medication can be helpful at low doses to make small reductions. Guidelines should recommend hyperbolic tapering while awaiting randomized trials comparing linear with hyperbolic tapering.

Formal guidelines recommend that opioids should be stopped when risks outweigh benefits. These guidelines generally recommend gradual dose tapering at a rate tolerable to the patient. However, there is considerable variation regarding the pattern of dose tapering recommended, with some suggesting linear tapers (with a fixed reduction of dose at each step), while others recommend increasingly small dose reductions as the total dose gets lower. No biological rationale has been put forward for these recommendations. We examined the pharmacodynamic properties of opioids to derive pharmacologically rational principles for tapering. As dictated by the law of mass action, the relationship between dose of opioid and effect on its principal target, the mu-opioid receptor, is hyperbolic, with diminishing incremental effects for increasing doses. This suggests that in order to mitigate withdrawal symptoms, opioid doses should be tapered according to a corresponding hyperbolic pattern, with dose reductions becoming increasingly small as total dose reduces. This can be approximated by proportional decreases (e.g. 1%–10% reduction of the most recent dose every 1–2 weeks). Dose reductions should be titrated to withdrawal symptoms throughout the process, and final doses before complete cessation will need to be very small (such as 0.1 mg of buprenorphine or 1 mg of methadone, or less). The duration required for this strategy of tolerable tapering after long-term use may require many months or years for some patients. The theoretical proposals in this paper offer a pharmacologically rational strategy that should prompt review of clinical practice and guidelines. Gradual, hyperbolic tapering should be evaluated in randomised controlled trials.

The author considers how the medical standard of care in depression treatment has shaped the course of her life. She recounts how she developed depression in childhood and, as a member of the demographic targeted by pharmaceutical marketing for antidepressants in the 1990s, how she came to be treated with the new selective serotonin reuptake inhibitor drugs, her experiences with her prescribers, and her recovery from disabling protracted antidepressant withdrawal syndrome. As a citizen scientist, she incorporates learnings from the history and practice of psychopharmacology and her own research into a personal narrative of what has become normal care for depression.

ObjectiveThe objective of this study is to identify the top 10 research priorities on reducing and stopping psychiatric medication that reflect the perspectives and unmet needs of three key stakeholder groups (people with lived experience, family members/carers/supporters and healthcare professionals).MethodsA priority-setting partnership was conducted using the James Lind Alliance’s seven-step process. This involved (1) creating an international Steering Group of key stakeholder representatives and (2) identifying potential partners; (3) gathering stakeholders’ uncertainties about reducing and stopping psychiatric medication using an online survey and summarising the survey responses; (4) checking the summary questions against existing evidence and verifying uncertainties; (5) shortlisting the questions using a second online survey; (6) determining the top 10 research questions through a prioritisation workshop; and (7) disseminating the results.ResultsA total of 3635 questions were collected in the initial survey from 884 respondents of which 32 questions were verified as uncertainties. These questions were then ranked in a second online survey by 526 respondents and the findings discussed in a final prioritisation workshop by 30 participants to produce the final top 10 list of research questions. These questions cover a range of areas including the most effective ways of safely reducing/stopping psychiatric medication and providing support to individuals undergoing the discontinuation process, as well as the best ways to educate healthcare professionals on this topic.ConclusionThe top 10 list of research priorities was produced through extensive engagement with key stakeholders and highlights important uncertainties and gaps in the existing evidence base that need to be addressed by future research.

Adaptation of the brain to the presence of a drug predicts withdrawal on cessation. The outcome of adaptation is often referred to as ‘physical dependence’ in pharmacology, as distinct from addiction, although these terms have unfortunately become conflated in some diagnostic guides. Physical dependence to antidepressants may occur in some patients, consistent with the fact that some patients experience withdrawal effects from these medications. It is thought that longer duration of use, higher dose and specific antidepressants affect the risk of antidepressant withdrawal effects as they might cause greater adaptation of the brain. We searched PubMed for relevant systematic reviews and other relevant analyses to summarise existing data on determinants of antidepressant withdrawal incidence, severity and duration. Overall, data were limited. From survey data, increased duration of use was associated with an increased incidence and severity of withdrawal effects, consistent with some evidence from data provided by drug manufacturers. Duration of use may be related to duration of withdrawal effects but data are heterogenous and sparse. Serotonin and noradrenaline reuptake inhibitors and paroxetine are associated with higher risks than other antidepressants, though data for some antidepressants are lacking. Higher doses of antidepressant has some weak association with an increased risk of withdrawal, with some ceiling effects, perhaps reflecting receptor occupancy relationships. Past experience of withdrawal effects is known to predict future risk. Based on these data, we outline a preliminary rubric for determining the risk of withdrawal symptoms for a particular patient, which may have relevance for determining tapering rates. Given the limited scope of the current research, future research should aim to clarify prediction of antidepressant withdrawal risk, especially by examining the risk of withdrawal in long-term users of medication, as well as the severity and duration of effects, to improve the preliminary tool for predictive purposes. Further research into the precise adaptations in long-term antidepressant use may improve the ability to predict withdrawal effects for a particular patient.

Background: There is a growing number of service users looking to discontinue use of psychiatric medicines. Tapering is the recommended approach for reducing and/or discontinuing the use of psychiatric medicines. This involves gradually reducing the dose over time to minimise the potential for withdrawal symptoms. However, many uncertainties exist regarding the process of reducing and stopping psychiatric medicines. This study will use a James Lind Alliance Priority Setting Partnership to determine the Top 10 unanswered questions and uncertainties about reducing and stopping psychiatric medicines. Methods: The Priority Setting Partnership will be conducted using the James Lind Alliance methodology. It will involve seven stages: (i) creating an international Steering Group of representatives from key stakeholder groups that will include people with lived experience of taking and/or stopping psychiatric medicines, family members, carers/supporters and healthcare professionals, and identifying potential partners to support key activities (e.g. dissemination); (ii) gathering uncertainties about reducing and stopping psychiatric medicines from key stakeholders using an online survey; (iii) data processing and summarising the survey responses; (iv) checking the summary questions against existing evidence and verifying uncertainties; (v) shortlisting the questions using a second online survey; (vi) determining the Top 10 research questions through an online prioritisation workshop; (vii) disseminating results. Conclusions: This study will use a Priority Setting Partnership to generate a Top 10 list of research questions and uncertainties about reducing and stopping psychiatric medicines. This list will help to guide future research and deliver responsive and strategic allocation of research resources, with a view to ultimately improving the future health and well-being of individuals who are taking psychiatric medicines.

Background: In the context of a recovery-oriented approach to mental healthcare, the role of psychotropic medication over extended or indefinite periods is increasingly being called into question. To minimise the risks of withdrawal symptoms and relapse, it is crucial that service users who want to discontinue psychotropic medication are supported throughout the tapering process. However, in the absence of effective interventions and supports, service users are increasingly relying on online resources for guidance and support. To date, the evidence base for mobile phone applications (‘apps’) and app-based interventions supporting discontinuation of psychotropic use has not been examined. This scoping review aims to examine the content, underpinning evidence base and impact of available mobile phone apps and app-based interventions to support psychotropic tapering. Methods: A scoping review will be conducted using the Joanna Briggs Institute guidance and results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA-ScR) guideline. Several electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, ACM and IEEE Xplore) will be searched from 2008 onwards. Searches of the major app stores will also be conducted, specifically Apple's App Store (iOS) and Google Play Store (Android). Following screening, key information will be extracted from the included studies and apps. Identified apps will be coded using the Behaviour Change Technique (BCT) Taxonomy. The findings will be described using narrative synthesis. Conclusions: This scoping review will provide a broad overview of available apps to support psychotropic tapering, including a summary of their content using the BCT Taxonomy. The review findings will guide future research relating to the development, implementation and evaluation of app-based interventions to support the tapering of psychotropic medication.

Although psychiatric drug withdrawal syndromes have been recognized since the 1950s – recent studies confirm antidepressant withdrawal syndrome incidence upwards of 40% – medical information about how to safely go off the drugs has been lacking. To fill this gap, over the last 25 years, patients have developed a robust Internet-based subculture of peer support for tapering off psychiatric drugs and recovering from withdrawal syndrome. This account from the founder of such an online community covers lessons learned from thousands of patients regarding common experiences with medical providers, identification of adverse drug reactions, risk factors for withdrawal, tapering techniques, withdrawal symptoms, protracted withdrawal syndrome, and strategies to cope with symptoms, in the context of the existing scientific literature.

Background: Protracted withdrawal syndrome (PWS) after stopping antidepressants (frequently also referred to as post-acute withdrawal syndrome or PAWS) has been described in a few case reports. However, a detailed quantitative analysis of specific symptom manifestations in antidepressant PWS is still lacking. Methods: We extracted patient narratives from a large English-language internet forum SurvivingAntidepressants.org, a peer support site concerned about withdrawal from antidepressants. PWS was ascertained based on diagnostic criteria proposed by Chouinard and Chouinard, specifically ⩾6 months of continuous antidepressant use, with emergence of new and/or more intense symptoms after discontinuation that last beyond the initial 6 weeks of acute withdrawal. We assessed medication history, outcome of PWS, and the prevalence of specific symptoms. Results: In total, n = 69 individual reports of protracted withdrawal were selected for analysis. At time of the subjects’ most recent reports, duration of PWS ranged from 5 to 166 months, mean = 37 months, median = 26 months. Length of time on the antidepressant causing protracted withdrawal ranged from 6 to 278 months, mean = 96 months, and median = 79 months. Throughout the withdrawal experience, affective symptoms, mostly anxiety, depression, emerging suicidality and agitation, were reported by 81%. Somatic symptoms, mostly headache, fatigue, dizziness, brain zaps, visual changes, muscle aches, tremor, diarrhea, and nausea were reported by 75%. Sleep problems (44%) and cognitive impairments (32%) were mentioned less frequently. These broad symptom domains were largely uncorrelated. Conclusion: PWS or PAWS from antidepressants can be severe and long-lasting, and its manifestations clinically heterogeneous. Long-term antidepressant exposure may cause multiple body system impairments. Although both somatic and affective symptoms are frequent, they are mostly unrelated in terms of occurrence. Proper recognition and detection of PWS thus requires a comprehensive assessment of medication history, duration of the withdrawal syndrome, and its various somatic, affective, sleep, and cognitive symptoms.