Search

Prescription rates for gabapentinoids are rising in England. Pregabalin is currently recommended by NICE for the treatment of anxiety. Gabapentinoids have some overlap with the action of benzodiazepines, and have similar issues with tolerance, dependence, addiction and withdrawal. They were scheduled as class C controlled drugs in 2019 because of these risks. There were 244 deaths due to poisoning recorded by the ONS in 2019 involving pregabalin. Poisonings due to pregabalin usually involve concomitant use of opioids or other drugs. The rate of deaths involving pregabalin has been rising steeply for the last 10 years, and now exceeds those attributed to diazepam, fentanyl, the tricyclics as a group or SSRIs as a group. Evidence for the use of pregabalin in anxiety is derived from short-term trials, with marginal differences from placebo, which do not take into account the longer term effects of tolerance, dependence and withdrawal. We call on NICE to re-evaluate their support for use of pregabalin in anxiety in light of its known harms. The use of gabapentinoids off-label for other psychiatric conditions should also be re-considered. In general, psychotropic medications require longer term efficacy and safety studies before allowing widespread use. [ABSTRACT FROM AUTHOR]

Background: Maintenance antipsychotic medication is recommended for people with schizophrenia or recurrent psychosis, but the adverse effects are burdensome, and evidence on long-term outcomes is sparse. We aimed to assess the benefits and harms of a gradual process of antipsychotic reduction compared with maintenance treatment. Our hypothesis was that antipsychotic reduction would improve social functioning with a short-term increase in relapse., Methods: RADAR was an open, parallel-group, randomised trial done in 19 National Health Service Trusts in England. Participants were aged 18 years and older, had a diagnosis of recurrent, non-affective psychotic disorder, and were prescribed an antipsychotic. Exclusion criteria included people who had a mental health crisis or hospital admission in the past month, were considered to pose a serious risk to themselves or others by a treating clinician, or were mandated to take antipsychotic medication under the Mental Health Act. Through an independent, internet-based system, participants were randomly assigned (1:1) to gradual, flexible antipsychotic reduction, overseen by treating clinicians, or to maintenance. Participants and clinicians were aware of treatment allocations, but assessors were masked to them. Follow-up was for 2 years. Social functioning, assessed by the Social Functioning Scale, was the primary outcome. The principal secondary outcome was severe relapse, defined as requiring admission to hospital. Analysis was done blind to group identity using intention-to-treat data. The trial is completed and has been registered with ISRCTN registry (ISRCTN90298520) and with ClinicalTrials.gov (NCT03559426)., Findings: 4157 people were screened, of whom 253 were randomly allocated, including 168 (66%) men, 82 (32%) women, and 3 (1%) transgender people, with a mean age of 46 years (SD 12, range 22-79). 171 (67%) participants were White, 52 (21%) were Black, 16 (6%) were Asian, and 12 (5%) were of other ethnicity. The median dose reduction at any point during the trial was 67% in the reduction group and zero in the maintenance group; at 24 months it was 33% versus zero. At the 24-month follow-up, we assessed 90 of 126 people assigned to the antipsychotic dose reduction group and 94 of 127 assigned to the maintenance group, finding no difference in the Social Functioning Scale (β 0·19, 95% CI -1·94 to 2·33; p=0·86). There were 93 serious adverse events in the reduction group affecting 49 individuals, mainly comprising admission for a mental health relapse, and 64 in the maintenance group, relating to 29 individuals., Interpretation: At 2-year follow-up, a gradual, supported process of antipsychotic dose reduction had no effect on social functioning. Our data can help to inform decisions about the use of long-term antipsychotic medication., Funding: National Institute for Health Research., Competing Interests: Declaration of interests JM has grants from National Institute for Health Research (NIHR) and is a co-applicant on grants from the Medical Research Future Fund (MRFF) in Australia. She receives royalties from six books about psychiatric drugs, she has received lecture fees from Alberta Psychiatric Association, British Psychological Association, Universite de Sherbrooke, Case Western Reserve University, and University of Basal. She is co-chair person of the Critical Psychiatry Network and a board member of the Council for Evidence-based Psychiatry (both unpaid roles). RC is an unpaid Board Member of the International Institute for Psychiatric Drug Withdrawal (IIPDW), has undertaken paid work for the All Party Parliamentary Group for Prescribed Drug Dependence, and is a member of the Advisory Board for the PARTANE Study (a paid role). NF has grants from NIHR, Medical Research Council, Cure Parkinson's Trust, and the EU. He has received consulting fees from ALK, Sanofi Avantis, Gedeo Richter, Abbott, Galderma, Astra Zeneca, Ipsen, Vertex, Thea, Novo Nordisk, and Aimmune, speaker fees from Abbott Singapore, and been paid to sit on a data safety monitoring or advisory board by Orion. GL is chair of an NIHR-funded trial steering committee. SJ has grants from NIHR and UK Research and Innovation. She is chair of programme advisory committees for two studies funded through NIHR Programme Grants and has acted as a paid reviewer of grant applications for programmes on social interventions for Austrian foundation–Wiener Wissenschafts-, Forschungs- und Technologiefonds (Vienna Science and Technology Fund). TB is joint head of the Prescribing Observatory for Mental Health, Royal College of Psychiatrists. MH is co-applicant on grants from the MRFF in Australia, he has received consulting fees from Outro Health, a digital clinic aimed to support people to stop unnecessary antidepressants, lecture fees from National Health Service Trusts for grand rounds presentations, Salomon's University and University of Washington. He sits on the data safety monitoring board of the RELEASE trial in Australia, and is a co-founder of Outro Health. He is a member of the Critical Psychiatry Network and IIPDW (both unpaid roles). SP has grants from NIHR. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Public Health England recently called for the establishment of services to help people to safely stop prescribed drugs associated with dependence and withdrawal, including benzodiazepines, z-drugs, antidepressants, gabapentinoids and opioids. NICE identified a lack of knowledge about the best model for such service delivery. Therefore, we performed a global survey of existing deprescribing services to identify common practices and inform service development., Methods: We identified existing deprescribing services and interviewed key personnel in these services using an interview co-produced with researchers with lived experience of withdrawal. We summarised the common practices of the services and analysed the interviews using a rapid form of qualitative framework analysis., Results: Thirteen deprescribing services were included (8 UK, 5 from other countries). The common practices in the services were: gradual tapering of medications often over more than a year, and reductions made in a broadly hyperbolic manner (smaller reductions as total dose became lower). Reductions were individualised so that withdrawal symptoms remained tolerable, with the patient leading this decision-making in most services. Support and reassurance were provided throughout the process, sometimes by means of telephone support lines. Psychosocial support for the management of underlying conditions (e.g. CBT, counselling) were provided by the service or through referral. Lived experience was often embedded in services through founders, hiring criteria, peer support and sources of information to guide tapering., Conclusion: We found many common practices across existing deprescribing services around the world. We suggest that these ingredients are included in commissioning guidance of future services and suggest directions for further research to clarify best practice., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RC is a Board Member of the International Institute for Psychiatric Drug Withdrawal (IIPDW) and JD an associate member. JD is a secretariat member of the All-Party Parliamentary Group for Prescribed Drug Dependence (APPG-PDD) and founding member of the Council for Evidence based Psychiatry. JM is co-chairperson of the Critical Psychiatry Network, a board member of the Council for Evidence-Based Psychiatry, chief investigator on the RADAR study of antipsychotic reduction funded by the UK government’s National Institute of Health Research (NIHR) and co-investigator on the REDUCE study of antidepressant discontinuation also funded by the NIHR. MH reports that he is co-founder of Outro Health a digital clinic which helps people safely stop unnecessary antidepressants in Canada and North America. He has been commissioned to write the Maudsley Deprescribing Guidelines in Psychiatry. He is co-investigator on the RELEASE trial in Australia investigating gradually stopping antidepressants in a hyperbolic manner. AG is an associate member of the IIPDW, a member of the Council for Evidence-based psychiatry, and the secretariat co-ordinator for the APPG-PDD secretariat 2016-19, 2020-present. MA, NM and JL declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials, although there are restrictions to data availability (please see data availability statement), (Copyright: © 2023 Cooper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In England, the prescribing of antidepressants, primarily the newer generation antidepressant classes, has steadily increased over recent years. There is ongoing debate about how the efficacy of these drugs is viewed, their place in therapy and the harms associated with stopping them. Much of the evidence of their efficacy comes from short-term placebo-controlled trials which tend not to include outcomes that are of greatest relevance to patients, such as social functioning or quality of life, but rather restrict outcomes narrowly to symptom measures. On such measures these studies do not demonstrate clinically significant differences from placebo for depression. A range of adverse effects are also recognised, often greater in naturalistic studies of long-term antidepressants users than those measured in short-term efficacy studies, including emotional numbing, sexual difficulties, fatigue and weight gain. There is increasing recognition that withdrawal symptoms from antidepressants are common and that these symptoms can be severe and long-lasting in some patients. Recent guidance on how to stop antidepressants in a tolerable way has been presented by the Royal College of Psychiatrists. We believe that increasing awareness about the difficulty that some patients have in stopping antidepressants should lead to more cautious prescribing practice, with antidepressants given to fewer patients and for shorter periods of time. This article discusses the perceived benefits and harms of antidepressant use., Competing Interests: Competing interests: None declared. Refer to the online supplementary files to view the ICMJE form(s)., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)