select search filters
briefings
roundups & rapid reactions
before the headlines
Fiona fox's blog
A study published in The Lancet Psychiatry looks at antidepressant discontinuation symptoms.
Prof Oliver Howes, Chair of the Psychopharmacology Committee at the Royal College of Psychiatrists, said:
“We welcome the insight that this robust study provides. It indicates that withdrawal symptoms can occur in about 1 in 6 people stopping antidepressant treatment, and that only about 1 in 35 might experience severe withdrawal symptoms.
“Antidepressants are a clinically recommended treatment, and they are effective at reducing the symptoms of moderate to severe depression, particularly when used in combination with talking therapies. It is important patients discuss their treatment options with a qualified practitioner, including their benefits, risks and side effects.
“Over the last 30 years our understanding of how different types of antidepressants work and the variation in side effects has grown considerably. As the body of evidence of withdrawal symptoms has improved, the College has pushed for changes to clinical guidance, to have a greater focus on safely managing withdrawal.
“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms. The College has produced a resource for patients and carers on stopping antidepressants, that offers information on how someone can taper their medication at a pace that suits them and their individual needs.”
Dr Sameer Jauhar, Senior Clinical Lecturer in Affective Disorders and Psychosis, Consultant Psychiatrist, King’s College, London and South London and Maudsley NHS Foundation Trust, said:
“There has been a lot of “debate” about the important problem of antidepressant withdrawal in the last few years, which has appeared within print and social media, with very high estimates of withdrawal being pronounced, at around 50%, and half as severe. This was based on a very unconventional review, which included data from online surveys, which are notoriously difficult to interpret (ask anyone involved in election polling).
“This new, thorough review and meta-analysis indicates rates are much lower, and also occur in people coming off placebo, as opposed to antidepressants. When accounting for placebo the rates of withdrawal symptoms are around 14%, and 2% for severe withdrawal. It should be acknowledged that this only pertains to those taking part in trials, though this is the best evidence we have.
“Clinically, doctors will still need to have conversations about stopping medications and doing this safely, though it will be gratifying to know rates of withdrawal are nowhere near s high as reported.
“This work is a salutary lesson, as some people may have been dissuaded from taking a potentially effective treatment, based on poor quality evidence that did not conform diligently to the scientific method.
“Science does correct itself, and the authors are to be congratulated on this work.”
Dr Eric Ruhé, Psychiatrist-epidemiologist, Department of Psychiatry, Radboud University Medical Center and Prof Christiaan Vinkers, Psychiatrist and Full Professor in the Department of Psychiatry, Amsterdam University Medical Center, said:
“This is an important study, following stringent methodology that indicates very clearly that the occurrence of discontinuation symptoms after withdrawal of antidepressants is an important topic to inform patients about and support them when these discontinuation symptoms occur. The incidence of discontinuation symptoms is around 31%, which includes substantial nocebo effects which also occur after placebo discontinuation (17%). This indicates that nocebo effects and anticipation are important factors, and that future research of antidepressant discontinuation require placebo-controlled studies in order to disentangle these effects.
Severe discontinuation symptoms occur much less (2.8%), but should be taken seriously, and are important as many millions of patients take antidepressants. Unclear is which patients will suffer from (severe) discontinuation symptoms. In the Dutch multidisciplinary document for discontinuation SSRIs and SNRIs (https://pubmed.ncbi.nlm.nih.gov/31230677/), consensus-based risk factors to determine slower tapering have been proposed and might guide decisions.
Dr Eric Ruhé: “Instead of causing undue alarm that all patients should be using slower tapering regimes when antidepressants are discontinued, these studies indicate that we need more empirical placebo-controlled studies to test who will develop discontinuation symptoms in order to tailor tapering schedules.”
Prof Christiaan Vinkers: “The current findings indicating antidepressant discontinuation symptoms in 1 out of every 6 to 7 patients are an important first step to help patients responsibly discontinue. However, this is evidence is based on studies that discontinue antidepressants abruptly or very fast (often in 1 of 2 weeks). Therefore, discontinuation symptoms may be lower in tapering schedules over several months that are currently often used. Moreover, the increasing evidence on stopping antidepressants is welcome and should lead to multidisciplinary guidelines to help clinicians and patients discuss and guide discontinuation.”
Prof Tony Kendrick, Professor of Primary Care, University of Southampton, said:
“Many of the studies included in the systematic review were not set up to study antidepressant discontinuation as a primary aim, but were efficacy studies comparing an antidepressant versus a placebo for a depressive or anxiety disorder, which also happened to observe patients in the wash-out period coming off the drugs at the end of the trials. Consequently, the period of taking the antidepressant was 12 weeks or less in 36 out of the 79 included studies (I observed this from the table of studies included as an appendix to the paper). This is a serious weakness which is not acknowledged in the paper, as severe discontinuation symptoms would not usually be expected to arise after only a few weeks of antidepressant use.
“The method of assessment of discontinuation symptoms in the included studies was very variable. A specific measure of discontinuation symptoms like the DESS was used in only six of 79 studies included in the review, and in most cases the assessment seemed to depend at least partly on the judgement of the authors of the included studies, rather than being based on a systematic collection of data. This would seem to me to make the assessment of the proportion of patients suffering severe symptoms particularly unreliable, as it was not the judgement of the patients being reported, but the judgement of the authors of the studies.
“There was no public or patient representation on the study, which if present might have made the authors consider at greater length these weaknesses in the studies in terms of the durations of antidepressant use and the methods of assessment of discontinuation symptoms.”
Prof Glyn Lewis, Professor of Epidemiological Psychiatry, UCL Division of Psychiatry, UCL, said:
“They have provided the best estimates so far about how many people experience discontinuation symptoms when they stop antidepressants. They also found that many people still experience ‘discontinuation symptoms’ after stopping placebo. It shows the importance of comparing antidepressants with placebo when studying discontinuation.”
Dr Paul Keedwell, Consultant Psychiatrist and Fellow of the Royal College of Psychiatrists, said:
“Doctors have been aware of the antidepressant withdrawal syndrome for some time. According to this meta-analysis of 79 randomised controlled trials, 85% of individuals will not experience withdrawal symptoms when stopping their antidepressant medication, and in most cases the symptoms will be mild. However, the average time to discontinuation in these studies was mostly less than 6 months, and as low as one week.
“Although this analysis did not provide information on the duration of withdrawal symptoms, other research suggests that they last for 1-2 weeks in most cases. Individuals who have been on their meds for a year or more will find it more difficult to come off them, and the withdrawal syndrome might last for months, and rarely up to a year.
“Individuals who are planning to stop their medication should always seek medical advice. This is important for two reasons:
“Firstly, depending on your mental health history, there might be a high risk of relapse of your depression. Sometimes a relapse of depression can be confused with withdrawal symptoms.
“Secondly, unpleasant withdrawal symptoms can be largely prevented with proper medical supervision. The medication can be withdrawn slowly or switched to a longer acting medication before stopping. Some antidepressants are more likely to cause withdrawal symptoms than others. Imipramine, paroxetine (Seroxat) and venlafaxine (Effexor) are particularly prone to causing them, while stopping fluoxetine (Prozac) is very unlikely to lead to significant problems.
“It is important to say that withdrawal symptoms are not dangerous, and the risk of experiencing them at some future date should not be a reason for refusing antidepressant treatment. The pros and cons of treatment should always be discussed with your doctor.”
‘Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis’ by name of first author et al. was published in The Lancet Psychiatry at 23:30 UK time on Wednesday 5th June.
DOI: doi.org/10.1016/S2215-0366(24)00133-0
Declared interests
Dr Sameer Jauhar: Dr Jauhar has received honoraria for educational talks given for Sunovian, Jannsen, Boehringer-Ingelheim and consulted for LB Pharmaceuticals, all based on antipsythoics and psychosis.
He is a Council Member for the British Association for Psychopharmacology and has sat on a funding panel for the Wellcome Trust and Health Technology Board for NICE, non tardive dyskinesia.
Dr Eric Ruhé: Dr Ruhe was a member of the task-force that drafted the Dutch multidisciplinary document for discontinuation SSRIs and SNRIs. Recently published about discontinuation across all classes of psychotropic drugs (https://pubmed.ncbi.nlm.nih.gov/38503923/). PI of the ongoing, placebo-controlled study “Trial Examining Methods for Antidepressant Discontinuation” (TEMPO), supported by ZonMW, Netherlands and contributed to the Dutch multidisciplinary Guideline Depression.
Prof Christiaan Vinkers: Dr. Vinkers is co-founder of the antidepressant discontinuation outpatient clinic in Amsterdam.
Recently published about discontinuation across all classes of psychotropic drugs (https://pubmed.ncbi.nlm.nih.gov/38503923/). PI of the ongoing, placebo-controlled study “Trial Examining Methods for Antidepressant Discontinuation” (TEMPO), supported by ZonMW, Netherlands and contributed to the Dutch multidisciplinary Guideline Depression.
Prof Tony Kendrick: I led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation, and was a member of the guideline committee for the NICE 2022 Depression Guideline.
Prof Glyn Lewis: Glyn Lewis acknowledges the support of National Institute for Health and Care Research (NIHR), the Wellcome Trust, UK Research and Innovation (UKRI), and University College London Biomedical Research Centre (UCLH BRC); grants from NIHR, the Wellcome Trust, and UKRI; and travel and accommodation to attend the European College of Neuropsychopharmacology 2023. Prof Glyn Lewis also co -authored the commentary piece accompanying this publication.
Dr Paul Keedwell: No conflicts