Most patients don’t have ‘severe’ antidepressant withdrawal, finds large study

A large evidence review has concluded that most people taking antidepressants do not experience ‘severe’ withdrawal symptoms.

The analysis by UK researchers found that while participants who stopped antidepressants did experience an average of one or more symptom than those who continued or were taking placebo, including dizziness and nausea, this was not enough to be clinically significant.

Yet in a strongly worded response to the paper, another group of UK experts said the paper was ‘flawed’ relying on short term pharmaceutical company trials.

That does not reflect real-world use of antidepressants which patients can be taking for many years, critics said.

The authors of the review, published in JAMA Psychiatry, said it was the largest study to date based on 50 high quality studies and would provide reassurance as well as highlighting the symptoms to look out for.

Overall, it included 17,828 participants, with an average age of 44 years, of whom 70% were female.

Across antidepressants, irrespective of the type taken, patients generally had around one extra symptom on a 43-symptom item scale when stopping the medication.

The most common symptoms when compared with placebo were dizziness (7.5% vs 1.8%), nausea (4.1% vs 1.5%), vertigo (2.7% vs 0.4%) and nervousness (3% vs 0.8%), the researchers reported.

A range of antidepressants was looked at in the study with researchers reporting the most symptoms were seen with discontinuance of venlafaxine, where approximately 20% of people suffered from dizziness, compared to 1.8% taking placebo.

With vortioxetine, fewer than one extra symptom was seen and no extra symptoms were seen with agomelatine, they said.

When non-placebo-controlled studies were also included, rates of symptoms increased slightly with dizziness reported by 11.8%, nightmares by 8.1%, nervousness by 7.6%, and nausea by 5.8% of patients.

The team said that relapse of depression was not seen in those withdrawing from antidepressants, even in people with existing depression.

Most of the studies included followed patients up for two weeks after they stopped taking the antidepressant.

Dr Sameer Jauhar, lead author, at Imperial College London, said: ‘Our work should reassure the public because we replicated other findings, from high-quality studies, and have highlighted the clinical symptoms to look out for.

‘Despite previous concern about stopping antidepressants, our work finds that most people do not experience severe withdrawal, in terms of additional symptoms.

‘Importantly, depression relapse was not linked to antidepressant withdrawal in these studies, suggesting that if this does occur, people will need to see their health professional to rule out a recurrence of their depressive illness.’

But the team added that while uncommon, there could be a sub-group of people who develop more severe withdrawal symptoms than the wider population of antidepressant users.

Dr Susannah Murphy, associate professor in the Department of Psychiatry at the University of Oxford, said the findings from the ‘comprehensive’ review could be helpful for clinicians to inform patients about potential effects, while also reassuring them that such symptoms are not common.

‘It’s important to note that the studies included only measured discontinuation symptoms in the first two weeks after stopping medication, so we still need more research to understand how long these effects might last.

‘The study was also not able to assess the severity of the symptoms, and this is important to consider in future studies.’

But Dr Mark Horowitz, lead author of the Maudsley Deprescribing Guidelines and visiting lecturer in Psychopharmacology at King’s College London said the study would ‘mislead’ the public and clinicians because many of the trials included had only lasted two to three months.

Dr Horowitz had authored a paper published in May which reported that taking antidepressants for more than two years is associated with a higher risk of withdrawal symptoms compared to short-term use.

‘In the UK about 4 million people take antidepressants for more than two years, and 2 million people take them for more than five years.

‘What happens to people in 8-12 week studies is a far cry from what happens to millions of people when they stop.’

Dr John Read, chair of the International Institute for Psychiatric Drug Withdrawal, also said the paper had methodological flaws.

‘Minimising the incidence of the withdrawal effects of antidepressants endangers patients’ safety.

‘It misinforms doctors, so they are less likely to recognise withdrawal effects and to provide proper support to the millions of people worldwide who are trying to come off their medication safely.’

A study published last year found that GPs could support almost half of patients taking long-term antidepressants to safely come off the drugs as long as they were well and willing to stop. 

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