A new review of research about antidepressant withdrawal has confirmed it does exist, but also reports that it's less common and severe than previously found.
Authors
Mark Horowitz
Honorary Clinical Research Fellow in Psychiatry, UCL
Joanna Moncrieff
Professor of Critical and Social Psychiatry, UCL
These findings feed into a growing debate about how common and severe withdrawal effects are. But we argue the researchers probably underestimate the incidence in long-term users who are most at risk of withdrawal effects.
One of the main limitations of this review is that it involved mostly short-term antidepressant users and therefore underestimates how common these symptoms are in people who take the drugs long-term. This is a growing group of people - and research shows they're most at risk of experiencing withdrawal.
The systematic review looked at 79 studies in total. Based on their analysis, the researchers reported that one in three people who stopped antidepressants experienced withdrawal effects. The authors also found that one in six people who'd been taking a placebo antidepressant reported experiencing withdrawal effects after stopping (often called the "nocebo" effect).
Taking this data into account, they concluded that about one in six people experienced withdrawal effects due to the antidepressants. The researchers also reported that only 3% of people demonstrated severe withdrawal effects, and they questioned whether some of these withdrawal effects were actually a return of people's underlying mental health problem.
Confirmation of antidepressant withdrawal will be welcomed by many people. While UK prescribing guidelines used to state withdrawal effects are typically mild and brief in most patients, tens of thousands of people have come forward in petitions, newspaper articles and on social media, reporting to have experienced severe withdrawal symptoms. Many describe problems including new-onset panic attacks, obsessive thinking, akathisia (a state of restlessness, agitation and terror) and profound risk of suicide.
In 2019, the first systematic review on antidepressant withdrawal found the picture was more congruent with what patients were reporting. The study found half of patients prescribed antidepressants experienced withdrawal effects - and half of these people reported severe symptoms.
Study limitations
The latest findings add to this picture, and it useful to have it confirmed that antidepressant withdrawal does occur and is not uncommon. But there are several reasons why they are not as reassuring as they seem.
First, the majority of studies included in the review were short-term studies conducted by drug manufacturers who have no incentive to detect withdrawal symptoms.
What's more, many of the studies were not designed to examine withdrawal and did so only incidentally or did not thoroughly assess withdrawal symptoms. This probably underestimated the incidence of withdrawal effects.
The average time people were on antidepressants in the studies included in the review was only 25 weeks. This is a far cry from how long many people use these drugs in clinical practice.
Half of patients in the UK who are on antidepressants have used them for more than two years - with 2 million people on them for than five years. In the US, half of people taking antidepressants are on them for more than five years.
We know that the longer people use antidepressants the more common and severe their withdrawal symptoms are when stopping. The authors of the paper reported that they found no relationship between how long people were taking antidepressants and risk of withdrawal effects but this is probably because they only looked at short-term studies, with very few studies lasting for more than a year.
One survey found that one in three people who had used antidepressants for three to six months reported withdrawal effects (similar to the results of the current meta-analysis) - with one-fifth reporting moderate or severe withdrawal effects.
For those who used antidepressants for more than three years, two-thirds reported withdrawal effects - and half reported these were moderate or severe. It's therefore likely the new review underestimates how common and severe withdrawal symptoms are for long-term antidepressant users.
The other major limitation of this review is that it assumed withdrawal effects from placebos and antidepressants were equivalent. However, symptoms were probably less intense in the placebo group.
In the few studies included in the review that did look at severity, people stopping antidepressants were seven times more likely to experience severe withdrawal effects as those stopping a placebo. Comparing the rates from these two groups is like comparing apples and oranges.
The review's authors also suggest that some of the reported withdrawal symptoms (such as emotional disturbance) may be a recurrence of the underlying mental health problem mistakenly classified as withdrawal. But it may be just as likely that some withdrawal symptoms could have been mis-classified as recurrence which may have meant they underestimated withdrawal effects.
And since depression is a fluctuating condition that comes and goes over time, it would be improbable for so many patients to relapse immediately after stopping antidepressants.
It's clear we need better quality research conducted in long-term users to more accurately know the risks. It's concerning that after decades of antidepressants being on the market so little attention has been paid to this major public health issue.
The risks of severe and long-lasting withdrawal effects should be taken into account when considering an antidepressant. These drugs should also be stopped more carefully than is normally done because of these risks.
Mark Horowitz is the author of the Maudsley Deprescribing Guidelines which outlines how to safely stop antidepressants, benzodiazepines, gabapentinoids and z-drugs, for which he receives royalties. He is co-applicant on the RELEASE and RELEASE+ trials in Australia funded by the NHMRC and MRFF examining hyperbolic tapering of antidepressants. He is co-founder and consultant to Outro Health, a digital clinic which helps people to safely stop no longer needed antidepressants in the US. He is a member of the Critical Psychiatry Network, an informal group of psychiatrists.
Joanna Moncrieff receives funding from the National Institute for Health Research for research projects. She is the author of three books about psychiatric drugs for which she receives royalties.
