Urgent need to find safe ways for patients to withdraw from antidepressants, survey finds

Despite millions of Australians taking antidepressants each day – using them at the second highest rate out of all OECD countries – there is little high quality evidence on safe and effective ways to stop treatment.

The findings come from the latest review published on Friday by the independent Cochrane institute, which examines scientific evidence to provide the most up-to-date and rigorous advice.

Cochrane researchers wanted to determine the best practice for assisting patients who no longer need antidepressants to come off them. They examined findings from 33 large and rigorous trials that combined included 4,995 participants who were prescribed antidepressants for 24 weeks or longer.

Lead author of the review, GP and emeritus professor of general practice at the University of Queensland, Mieke van Driel, said the researchers compared different approaches and looked at benefits, such as successful stopping rates, and harms reported during and after stopping. Withdrawal symptoms and harms reported during stopping included insomnia, low mood, anxiety and changes to appetite, but these can also be symptoms of a return of depression.

“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,” van Driel said. “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.”

In 13 of the studies examined by van Driel and her team, the antidepressant was stopped abruptly, while in 18, dosage was reduced gradually over a few weeks until it was stopped, a process known as ‘tapering’. In four of the studies, psychological therapy support was also offered.

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 guidelines from the UK Royal College of Psychiatrists updates in 2020 that recommends tapering “over months or longer”. Meanwhile, the Royal Australian and New Zealand College of Psychiatry’s guidelines are more vague saying: “When patients have received maintenance antidepressant medication, cessation of medication should occur slowly with a taper over an extended period of time because withdrawal symptoms may be experienced”.

Australian Institute of Health and Welfare data shows 4.3 million people received mental health-related prescriptions in 2018-19, more than 70% of which were for antidepressants.

Van Driel said it made it all the more concerning that there was no strong evidence for coming off them. Clinical guidelines were currently based on “consensus” among specialists, rather than strong scientific evidence, she said.

“It is shocking, and this review also helps draw attention to the question of why people are staying on antidepressants for so long,” she said. “Especially since guidelines recommend that most people with simple episodes of depression would take them for about six to 12 months, after which you review their medication when and look at if things have stabilised and if you can stop.”

The Cochrane review said there is an “urgent” need to conduct studies to find safe and effective approaches for people who want to stop taking them.

“In the meantime, we hope this review provides a starting point to help GPs openly discuss continuing or stopping antidepressants with their patients,” van Driel said. “We also want to raise awareness that withdrawal symptoms from antidepressants are common and can be mistaken for relapse of the underlying condition.”

Co-director of health and policy at the University of Sydney’s Brain and Mind Centre, Prof Ian Hickie, agreed more research was needed. He said adding to the complexity of ceasing medication was that everyone’s mental illness, symptoms, reasons for stopping and circumstances were different and might require tailored approaches.

“One of the issues we have worldwide is post-marketing surveillance of drugs,” Hickie said. “The Covid-19 vaccine has shown the importance of and what can be done with comprehensive post-market surveillance. But traditionally we haven’t invested with other drugs in the ‘what happens next’ stage including how to stop drugs.

“However, we have to remember the conditions antidepressants are used to treat aren’t always the same, and even antidepressants within the same class of drugs aren’t the same. They have different pharmacology and have different half-lives. So this is partially why it’s an understudied area worldwide.”


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