One in six people who come off antidepressants will experience withdrawal symptoms as a direct result, according to the most comprehensive study to date into the problem.

Researchers estimate that the effects of discontinuing the drugs will be severe for one in 45 patients, which can include feelings of dread and anxiety, insomnia, loss of libido and sexual function, brain zaps, dizziness, and suicidal thoughts.

The findings, published in the journal Lancet Psychiatry, are based on a meta-analysis of 76 existing papers comparing outcomes among 21,000 patients on a range of different antidepressants or a placebo - an inert "dummy" drug.

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Previous studies have suggested that antidepressant withdrawal may occur in as many as half of cases, but many of these estimates are based on observational studies where it is more difficult to determine cause and effect or from surveys which can be skewed by selection bias - where patients with negative experiences are more motivated to respond.

A petition to the Scottish Parliament calling for more help for patients experiencing prescription drug dependence and withdrawal previously attracted hundreds of submissions from people who had experienced permanent and debilitating symptoms after stopping antidepressants.

In 2023, NICE issued updated guidance on tapering - gradually reducing doses over time - to help patients reduce their risk of withdrawal effects. 

The Lancet review included 44 randomised control trials (RCTs) - where patients were unaware whether they were taking a real antidepressant or a placebo - plus 35 observational studies.

Seven on 10 of the participants were female, and the average age was 45.

It found that withdrawal symptoms occurred in 31% of the patients who had been taking an antidepressant, with severe symptoms in 2.8% of cases, compared to an incidence of 17% and 0.6% respectively among those on a placebo.

Christopher Baethge, a professor of psychiatry at the University of Cologne, who led the research, said this meant that roughly one in six people experiencing withdrawal symptoms after taking antidepressants could put it down to having a pharmacological cause.

He said that it was likely that the patients reporting adverse effects despite having been on the dummy drug were experiencing the "nocebo effect", where they "expect bad things to happen once you take a drug, or in this case you don't take the drug any longer".

The Herald: Awareness of potential withdrawal symptoms linked to stopping antidepressants has been increasing in recent yearsAwareness of potential withdrawal symptoms linked to stopping antidepressants has been increasing in recent years

This can be influenced by a "heightened awareness" of antidepressant withdrawal symptoms (ADS) as a result of participating in a trial, said Prof Baethge.

He said: "If patients believe they have received antidepressants and have been informed prior to the study that ADS may occur, that may be one explanation...We are not saying it's 'all in their heads' - for example, patients do truly feel dizzy, no matter what the cause is.

"And we're not saying there's no problem [with ADS]. ADS are real and patients need to be informed."

Prof Baethge added that in some cases the symptoms detected would reflect the natural "background noise" affecting any population at any given time, such as headaches, flu-like symptoms, insomnia, and difficulty concentrating, so it was also important to distinguish when this was being directly caused by antidepressant withdrawal compared to chance.

Overall, the analysis found that the incidence of discontinuation symptoms was lowest for patients using sertraline and fluoxetine - better known by the brand names Zoloft and Prozac, and among the most commonly prescribed antidepressants in the UK.

They also found "no material association" between the length of time patients had been taking antidepressants and their probability of experiencing withdrawal.

The Herald: The researchers said the findings should provide some reassurance to patients and doctors that withdrawal may be less common than previously thoughtThe researchers said the findings should provide some reassurance to patients and doctors that withdrawal may be less common than previously thought (Image: This content is subject to copyright.)

Co-author Dr Jonathan Henssler added: "It’s important both doctors and patients have an accurate, evidence-based picture of what might happen when patients stop taking antidepressants.

"Our study confirms that a number of patients coming off antidepressants will experience discontinuation symptoms, and for a few, these will be of a more severe extent.

"However, our findings, which consolidate data from a large number of studies, should also provide reassurance that rates of discontinuation symptoms are not as high as some previous single studies and reviews have suggested.”

In a linked commentary, Glyn Lewis and Gemma Lewis - researchers from University College London who were not involved in the study - said the findings highlight the importance of including a placebo control arm in studies into withdrawal rates.

They added: “Reports of withdrawal symptoms that are not compared with a placebo will give a large overestimate of the frequency of such symptoms.”