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When “I feel well enough” is not enough: findings from a discontinuation of antidepressants trial

It’s a question often asked while on antidepressants: Can I stop taking these pills? For many people who feel well while on maintenance antidepressant therapy, there’s always the question of whether they’d continue to feel okay when weaned off the medications. There has been little research on the risk of relapse after discontinuing therapy in patients who’ve been on maintenance antidepressant therapy for longer than 8 months. A recently published study, however, found that people who tapered off prolonged maintenance antidepressant therapy were more likely to relapse than those who continued drug therapy.

The findings from the September 30, 2021 issue of the New England Journal of Medicine almost sounds like a no-brainer: duh, people with a long-standing history of depression taken off antidepressant medications will do poorly compared to similarly-matched people who continue on antidepressants. But the findings are both revealing and sobering.

When “I feel well enough” is not enough

The 478 patients enrolled in the study had long-standing depression with multiple recurrences, had been on continuous drug therapy for at least two years, but (and here’s the kicker) they felt well enough to consider stopping their medication. To test this assumption, participants were randomized to continue drug therapy or to taper and stop their antidepressants. One year after stopping the antidepressants, more than half (56%) of the participants relapsed, compared to 39% in the maintenance antidepressant group.

Sadly, depression relapse is not uncommon, especially for those who’ve had prior depressive episodes and the risk increases for every subsequent episode. The findings from this recent study highlights not only the risks involved in stopping maintenance antidepressant treatment in people with long-standing depression but also the challenges in remission maintenance for matched-peers who remain on treatment.

While the results are disappointing, they should be considered in the context of the studied patient population. Since participants of this study had a well-established history of depression, it’s unclear if these findings are applicable to people with a first episode of depression. While study participants felt well enough to go off medication, it’s also unclear how long they were in remission prior to starting the trial. It’s also worth mentioning that nondrug therapies (such as cognitive behavioral therapy) which can help prevent relapses in people who discontinue drug treatment, were not offered in this study.

To stop or not to stop

Ultimately, the decision to stop or not to stop antidepressant therapy is on a case by case basis. This study suggests that the “I feel well enough to stop” conviction is an inadequate litmus test to discontinue antidepressants in those with a longstanding history of depression. While the decision to wean off antidepressants may be prompted by conviction, it should be made in partnership with a mental health provider who knows your clinical history well. Ideally, there should be appropriate psychotherapy support in place. Any trial to discontinue antidepressants requires close physician followup for any depressive symptoms. Close partnership with a licensed mental health provider who knows you well can help increase the odds of “I feel well enough to stop” to “I am well off of antidepressants.”


Lewis G et al. Maintenance or discontinuation of antidepressants in primary care. N Engl J Med 2021 Sep 30; 385:1257.

Moriarty AS et al. Predicting and preventing relapse of depression in primary care. Br J Gen Pract 2020;70:54-55.

Geddes JR et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003;361:653-661.

​​Hollon SD et al. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Arch Gen Psychiatry 2005;62:417-422.


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