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Only one in six patients experience direct antidepressant withdrawal, study finds

Only one in six people who stop taking antidepressants will experience withdrawal symptoms as a direct result, according to a new study.

This is a much lower proportion than other studies have suggested, with previous estimates that over half of patients experience symptoms.

The research, published in the journal The Lancet Psychiatry, found that overall one in three patients reported at least one withdrawal symptom such as dizziness, headache or nausea.

But around one in six patients experienced the same symptoms when they stopped taking a placebo drug, suggesting that ‘approximately half of all symptoms experienced […] might be due to negative expectations (the “nocebo effect”) or non-specific symptoms which may occur at any time in the general population’.

The authors therefore concluded that ‘one in six to seven’, or 15%, of patients will experience one or more withdrawal symptoms as a direct result of stopping antidepressants.

Around one in 35 people (3%) will likely experience ‘severe symptoms’, the study also found.

According to the authors, this is the first meta-analysis on the incidence of antidepressant discontinuation symptoms, which analysed 79 randomised trials and included data from over 21,000 patients, of which 72% were women.

The researchers highlighted that patients and clinicians should make joint decisions about whether to discontinue antidepressants, and that patients should be monitored and supported throughout this process.

Study author Professor Christopher Baethge, from the psychiatry and psychotherapy department at the University of Cologne, said it is important that patients can access accurate, evidence-based information under the care of a doctor to discuss the balance of benefit and risk, including withdrawal. 

‘We hope the findings from this study will inform healthcare professionals and patients about the risk of experiencing discontinuation symptoms when stopping antidepressants without causing unnecessary alarm,’ he said.

‘Our findings do not imply that some symptoms experienced by people during antidepressant discontinuation are not “real“ or that all discontinuation symptoms are due to expectations on the part of patients.

‘Any symptoms that cause patients discomfort or distress should be taken seriously, and the patient should be supported. The patient and clinician should discuss which of the symptoms might be directly caused by stopping antidepressants and how best to manage all symptoms.’

The authors did note that a ‘challenge’ in all studies on antidepressant discontinuation is the chance that symptoms of ‘re-occuring depression’ are mistaken for discontinuation symptoms. 

Dr Sameer Jauhar, senior clinical lecturer in affective disorders at psychosis at King’s College, said there has been much debate about antidepressant withdrawal in recent years, with ‘very high estimates’ of withdrawal symptom incidence of around 50%. 

‘[This high estimate] 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),’ he said.

Dr Jauhar said this ‘thorough’ review only uses data from those taking part in trials, but highlighted that ‘this is the best evidence we have’. 

He added: ‘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 as high as reported.’

However, Professor Tony Kendrick, professor of primary care at the University of Southampton, said that many of the studies included in the systematic review were ‘not set up to study antidepressant continuation as a primary aim’.

He said: ‘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.’

In 2022, NICE concluded that antidepressants are not ‘dependence-forming’ drugs, although they can cause withdrawal symptoms.

A version of this article was originally published by our sister publication Pulse.

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