Cochrane review finds ‘urgent shortage’ of evidence around safe withdrawal from antidepressants

Researchers said that, owing to a lack of studies on discontinuing long-term antidepressants, they could not make firm conclusions about the effects and safety of the approaches studied to date.

More research into the deprescribing of long-term antidepressants is urgently needed — particularly in primary care — to determine the safest and most effective approach, a Cochrane review has concluded.

Researchers reviewed 33 randomised controlled trials, published up until January 2020, involving a total of 4,995 participants with depression and anxiety, who had been prescribed antidepressants for at least six months.

Nearly all studies were conducted in a specialist mental healthcare service and included participants who had experienced two or more episodes of depression prior to discontinuation.

Overall, 13 of the studies reported “abrupt” discontinuation of antidepressants, while 18 used “tapering” to reduce the dosage over one week or longer, with most lasting four weeks or fewer.

Four studies reported providing psychological support while discontinuing antidepressants and one considered the impact of a letter to the patient’s GP to review antidepressant treatment.

However, none of the studies used low‐intensity psychological interventions, such as online support or a changed pharmaceutical formulation that allowed tapering with low doses over several months.

The review follows the publication of guidelines by the Royal College of Psychiatrists in September 2020, which recommend tapering antidepressants over a period of months or a year, depending on the dose and how long the individual has been taking them.

The researchers said that, owing to the small number of studies focused on approaches to discontinuing long-term antidepressants, they could not make any firm conclusions about effects and safety of the approaches studied to date.

“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,” said Ellen Van Leeuwen from the clinical pharmacology unit at the University of Ghent, Belgium, and lead author of the study.

“For example, there are over 1,000 studies looking at starting antidepressants, yet we found only 33 trials around the world that examined stopping them. It’s clear that this area needs urgent attention.”

Tony Kendrick, professor of primary care at the University of Southampton and co-author of the study, added that “more than one in ten adults in England” were now taking antidepressants, but that surveys of long-term users suggest that between a third and a half of these had no evidence-based reason to continue taking them.

The authors said that that there is “an urgent need” for trials that “adequately” addressed withdrawal confounding bias and carefully distinguished relapse symptoms from withdrawal symptoms.

They added that withdrawal symptoms, such as low mood and dizziness, could have an effect on almost every outcome, including adverse events, quality of life, social functioning and severity of illness.

Adrian James, president of the Royal College of Psychiatrists, said that antidepressants could be a “lifeline” for people whose depression has a clear detrimental impact on their quality of life; for those with severe depression; and for patients where other treatment options have not worked.

“Some people experience withdrawal symptoms when trying to come off them, and reducing the dose slowly before stopping — also known as tapering — can help,” he said. “The more we understand about side effects, withdrawal symptoms, and how to reduce them, the more people we will be able to help.”

READ MORE: We designed a new way of tapering antidepressants, but why won’t the health authorities recognise its value?

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Citation
The Pharmaceutical Journal, April 2021;Online:DOI:10.1211/PJ.2021.1.80077