Discontinuation vs continuation of long-term antidepressant use

Over 7million (or 1 in 6) English adults take antidepressants every day, making England one of the highest consumers of antidepressants in the world. A new Cochrane review found little high quality evidence on safe and effective approaches for quitting. Comments by the MetroDaily Mail, and Guardian.

PRESS RELEASE BELOW…

‘We know the rise in long-term antidepressant use is a major concern around the world,’ says lead review author and Belgian-based researcher, Dr Ellen Van Leeuwen. ‘As a GP myself, I see first-hand 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 1,000 studies looking at starting antidepressants, yet we found only 33 randomised controlled trials (RCTs) around the world that examined stopping them. It’s clear that this area needs urgent attention.’

‘For me this is such a critical issue both from a personal and a professional perspective,’ says UCL-based researcher and training psychiatrist Dr Mark Horowitz. ‘I’m one of the hundreds of thousands of people who have had or are having long, difficult and harrowing battles coming off long-term depressants because of the severity of the withdrawal effects. And yet rather than being able to find or access any high quality evidence or clinical guidance in this situation, I could only find useful information on peer support sites where people who had gone through withdrawal from antidepressants themselves have been forced to become lay experts. Since then the Royal College of Psychiatrists has taken a great step forward in putting out guidance on Stopping Antidepressants in 2020. However, the is still a lack of research and therefore evidence in this area on what works for different people. I want other people to have the evidence on how to come off without the same trouble I had.’ 

In 2020, there were 78 million prescriptions provided for antidepressants across England to at least 7.3 million people. Half of patients who are on these medications are on them for more than two years. 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, but many people take antidepressants for much longer. Surveys of antidepressant users suggest that 30% to 50% of long-term antidepressant prescriptions have no evidence-based or 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, low blood sodium and gastrointestinal bleeding, as well as feeling emotionally numb and unable to deal with problems in life without medication.

Cochrane researchers looked at the findings from 33 RCTs that included 4,995 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 GPs 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 or years to safely stop.

‘We compared different approaches 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),’ says Dr Van Leeuwen. ‘Our review outlines detailed findings across all these areas, but in a nutshell there was only very low certainty 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 issue is that studies do not distinguish between symptoms of a return (or relapse) of depression and symptoms of withdrawal after stopping, and that’s really problematic.’

Dr Horowitz says ‘The difficulty of distinguishing between withdrawal symptoms and relapse presents a real challenge for patients, doctors and researchers alike. Withdrawal symptoms from antidepressants include low mood, anxiety, and trouble sleeping. This can look a lot like relapse of anxiety and depression and we know that doctors and patients often mistake withdrawal symptoms for relapse. This has negative consequences because when doctors mistake withdrawal symptoms for relapse they can advise continuing the antidepressant, sometime life-long. This is an inappropriate response – the correct response would be to try coming off the antidepressant more slowly. Patients have started making direct appeals to doctors to please pay more attention to the issue.

This is also a problem in studies where antidepressants are stopped and relapse is measured. Patients in these studies are often stopped from their antidepressant over a few days or weeks and withdrawal symptoms are ignored. This might make it look like more people are having a return of their anxiety or depression than is really the case. This means that the studies upon which we currently recommend long-term treatment with antidepressants are unreliable.’

Dr van Leeuwen says ‘To address this critical issue and provide the evidence we need, future studies need to distinguish carefully between withdrawal symptoms and relapse, and try using taper schemes of many weeks or months (or longer for long-term users) down to very low doses before stopping. These kinds of studies would give us a clearer idea if we need to continue antidepressants to prevent relapse.’

‘Ultimately we really need more studies of stopping antidepressants – especially in primary care given that’s where most prescribing takes place – before we can make more definitive conclusions. In the meantime, we hope this review provides a starting point to help GPs 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.’

‘Looking ahead, we await the results of current studies underway that are looking at discontinuing antidepressants, such as the REDUCE trial in the UK, which is testing online and phone psychological support for patients withdrawing from long-term antidepressants, where this is appropriate,’ Dr Van Leeuwen says. ‘We know future studies will be critical in addressing the urgent need for more and better evidence, given the concerning trend of long-term use of antidepressants here in England and around the world.’

  • Ends –

 

Media contact:

Dr Mark Horowitz

Co-author, training psychiatrist and researcher

University College London

m.horowitz@ucl.ac.uk

Ph: 07767 630 317

 

Dr Ellen van Leeuwen

Lead author, GP and researcher

Ghent University, Belgium

Ellen.VanLeeuwen@UGent.be