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Research shows that over half of patients well enough to stop antidepressants have relapse

Discontinuing antidepressants in patients feeling well enough to stop led to a higher rate of depression relapse compared with continued therapy.

Depression is a global problem thought to affect around 280 million people or 5% of adults. The causes of depression are multifactorial and can involve a complex interaction between social, psychological, and biological factors. Treatment can be achieved through cognitive behavioural therapy as well as the use of antidepressants.

However, among those prescribed antidepressants, once a patient feels better in themselves, should they stop treatment or continue? This was the question posed by a UK team of researchers who looked at primary care patients who considered that they were now well enough to stop antidepressant treatment.

The team recruited adults prescribed conventional doses of three commonly used antidepressants: citalopram, sertraline and fluoxetine. In addition, eligible patients were those who had reported at least two prior episodes of depression or who had been taking antidepressants for more than two years.

Patients were then randomised 1:1 to either maintenance of their current antidepressant (maintenance group) or tapering and discontinuing (discontinuation group). Treatments were provided in identical bottles so that patients were unaware of whether they were assigned to the maintenance or discontinuation arm. In the discontinuation arm, the dose of antidepressant drug was reduced over a two month period so that by the third month they were taking placebo.

The primary outcome was the first relapse of depression during a 52 week follow-up period. There were eight secondary outcomes including depressive symptoms using the Patient Health Questionnaire 9-item (PHQ-9), as well as measures of anxiety and quality of life.


A total of 478 patients with a mean age of 54 years (75% women) were enrolled and randomised to either maintenance (238) or discontinuation of therapy. By week 52, relapse had occurred in 39% of those in the maintenance group but more than half, 56%, in the discontinuation group (hazard ratio, HR = 2.06, 95% CI 1.56 – 2.70, p < 0.001). The secondary outcomes were all generally in the same direction.

The authors concluded that even though all patients believed that they were well enough to discontinue with their antidepressants, doing so resulted in a higher risk of depression relapse. In addition, quality of life and symptoms of depression and anxiety were all worse in those who stopped treatment.


Lewis G et al. Maintenance or Discontinuation of Antidepressants in Primary Care. N Eng J Med 2021.