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Lack of evidence on safety of antidepressant withdrawal methods, study finds

By Beth Gault

27 Apr 2021

There is little evidence that the current approaches for stopping long term antidepressant use are safe and effective in people with recurrent depression, according to a recent study.

The recently published Cochrane review looked at 33 studies with 4,995 adult participants, which recorded different methods of antidepressant withdrawal, including stopping abruptly and stopping gradually over several weeks – or tapering.

Guidelines currently recommend that an antidepressant should be continued for at least six months after patients start feeling better, and for at least two years if they have had two or more periods of depression.

The review concluded that the evidence in this area was ‘very problematic’ and it was uncertain whether the methods studied to date are effective and safe in people with recurrent depression.

In a blog on the review, co-author Ellen Van Leeuwen, said: ‘The rise in long term antidepressant use is a major concern. For example, in the UK nearly half of people using antidepressants (8% of the total population, approximately 3.7 million people) have been taking them for more than two years.

‘Antidepressants that, despite initially being appropriate, are not discontinued after the recommended duration can lead to unnecessary harm and costs.’

She added: ‘Honestly, the evidence in this area is very problematic. It is not possible to make any firm conclusions about the effects and safety of the approaches for discontinuation studied to date. There were only a few studies with a focus on successful antidepressant discontinuation rate.

‘The main problem is that studies did not distinguish between symptoms of relapse of depression and symptoms of withdrawal after discontinuation.’

Withdrawal symptoms can include insomnia, low mood, anxiety and changes to appetite, but they are also recorded on the depression scales used to detect relapse. This could ‘inflate’ the rate of relapse in groups that stop antidepressants, according to co-author Mark Horowitz.

He added: ‘Additionally, most tapering regimes were limited to four weeks or less, in contrast to NICE guidelines recommending tapering over four weeks or more. In fact, there is now increasing recognition that antidepressants might need to be tapered over months or longer than a year to very low doses for long-term users.’

The authors said, despite the inconclusive data, the study would enable clinicians to openly discuss options with their patients, with the potential benefits or harms of continuing or stopping antidepressant use, but that more research was urgently needed.

Ms Van Leeuwen said: ‘This review reinforces the call for more research in the primary care setting, particularly for people with low risk of relapse and those for whom there is uncertainty about the benefit of antidepressant treatment.’

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