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Am Fam Physician. 2022;105(4):online

Clinical Question

For patients who are currently taking an anti-depressant and are doing well, what is the likelihood of relapse after discontinuation of their medication?

Bottom Line

Primary care patients who discontinued antidepressant medications were more likely to experience relapse of their depression (number needed to harm [NNH] = 6) than those who continued to take their antidepressants. The interpretation is that 44% of patients with depression who discontinue their antidepressant medication when they are doing well continue to do well. (Level of Evidence = 1b−)


The researchers identified primary care patients who had at least two episodes of depression or had been taking antidepressants for at least two years. All patients felt well enough to consider discontinuing their medication; those with current depressive symptoms were excluded. The patients who had been taking citalopram (Celexa), 20 mg; fluoxetine (Prozac), 20 mg; sertraline (Zoloft), 100 mg; or mirtazapine (Remeron), 30 mg for at least nine months were randomized to continue their medication or discontinue their medication by substituting a placebo over a two month period. At baseline, the mean age of participants was 54 years, 73% were women, 95% were White, approximately one-half were taking citalopram, and approximately three-fourths had been taking an antidepressant for more than three years. The primary outcome was relapse of depression, defined as feeling sad, miserable, depressed, or being unable to enjoy or take an interest in things as much as usual, accompanied by at least one other depressive symptom for two weeks. After one year, this outcome occurred significantly more often in the placebo group (56% vs. 39%; hazard ratio = 2.06; 95% CI, 1.56 to 2.70; NNH = 6). Depression and anxiety symptoms were, on average, more severe in the discontinuation group. More patients in the discontinuation group stopped taking the placebo (48% vs. 30%; hazard ratio = 2.28; 95% CI, 1.68 to 3.08) and resumed antidepressant medications (39% vs. 20%). The mean scores on the 7-item Generalized Anxiety Disorder Questionnaire and the 9-question Patient Health Questionnaire were higher in the discontinuation group.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (primary care)

Reference: Lewis G, Marston L, Duffy L, et al. Maintenance or discontinuation of antidepressants in primary care. N Engl J Med. 2021;385(14):1257–1267.

Editor’s Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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