Ghent University: Dramatic shortage of evidence for safe stopping from antidepressants

More than 12% Belgian adults take antidepressants every day, making Belgium the seventh highest consumer of antidepressants of all OECD countries. In a new review, Ghent University researchers highlight that while much is known about the increasing global uptake of antidepressants, there is very little evidence on safe and effective approaches to stop treatment.

Long-term antidepressant use puts people at risk
‘We know the rise in long-term antidepressant use is a major concern around the world. As general practitioner I see the struggles many patients have coming off antidepressants. It’s of critical concern that we don’t know enough about how to reduce inappropriate long-term use or what the safest and most effective approaches are to help people do this. For example, there are over 1000 studies looking at starting antidepressants, yet we found only 33 randomised controlled trials around the world that examined stopping them. It’s clear that this area needs urgent attention”, says lead author and Ghent University researcher, Ellen Van Leeuwen.
In 2017, 12% of Belgian adults took antidepressants, of which 29% longer than one year. Guidelines typically recommend that antidepressants be taken up to 6-12 months after improvement, or for up to 2 years in people at risk of relapse. However, many people take antidepressants for much longer. Surveys of antidepressant users suggest that up to half of the people on long-term antidepressant prescriptions have no clear medical reason to keep taking them. Long-term use can put people at risk of adverse events such as sleep disturbance, weight gain, sexual dysfunction, bleeding and gastrointestinal problems, as well as feeling emotionally numb and unable to deal with problems in life without medication.

New review on stopping with antidepressants
For this new Cochrane study, researchers looked at the findings from 33 randomised controlled trials that included 4995 participants who were prescribed antidepressants for 24 weeks or longer. In 13 studies, the antidepressant was stopped abruptly; in 18, it was stopped over a few weeks (known as ‘tapering’); in four, psychological therapy support was also offered; and in one study, stopping was prompted by a letter to general practitioners with guidance on tapering. Most tapering schemes lasted four weeks or less and none of the studies used very slow tapering schemes beyond a few weeks – in contrast to new guidelines from the UK Royal College of Psychiatrists that recommend tapering over months to safely stop.

The researchers compared different approaches versus continuation of long-term antidepressants and looked at benefits (such as successful stopping rates) and harms (such as return of the depressive or anxiety episodes, side effects and withdrawal symptoms). Their review shows that there was only very low evidence on the pros and cons of each of the different approaches to stopping – making it difficult to reach any firm conclusions at this time. The key problem is that previous studies have not distinguished between symptoms of a return (or relapse) of depression and symptoms of withdrawal after stopping the antidepressant.

Withdrawal symptoms or relapse?
Cochrane Study AntidepressantsThe difficulty of distinguishing between withdrawal symptoms and relapse presents a real challenge for patients, doctors and researchers alike – often resulting in inappropriate continuation of antidepressant medication and uncertain evidence on which to base healthcare decisions. For example, in studies where antidepressants are stopped, withdrawal symptoms such as insomnia, low mood, anxiety and changes to appetite were interpreted as a return of the patient’s anxiety or depression. This might make it look like more people are having a return of their anxiety or depression than is really the case.

To address this critical issue, more research is needed to establish the incidence of withdrawal symptoms in patients, and large randomised controlled trials are needed to test different tapering strategies. Ultimately, more discontinuation studies are needed – especially in primary care given that’s where most prescribing takes place –before more definitive conclusions can be made. In the meantime, the authors hope this review provides a starting point to help doctors openly discuss continuing or stopping antidepressants with their patients.

“We want to raise awareness that withdrawal symptoms from antidepressants are common and can be mistaken for relapse of the underlying condition. Experiencing withdrawal symptoms isn’t necessarily a sign that the patient has relapsed – it might be that they need to taper more gradually down to much lower doses instead, before eventually stopping”, says Ellen Van Leeuwen.

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