• Gemma Lewis, Louise Marston, Larisa Duffy, Nick Freemantle, Simon Gilbody, Rachael Hunter, Tony Kendrick, David Kessler, Dee Mangin, Michael King, Paul Lanham, Michael Moore, Irwin Nazareth, Nicola Wiles, Faye Bacon, Molly Bird, Sally Brabyn, Alison Burns, Caroline S Clarke, Anna Hunt, Jodi Pervin, and Glyn Lewis.
• From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.).
• N. Engl. J. Med. 2021 Sep 30; 385 (14): 1257-1267.

BackgroundPatients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting.MethodsWe conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings.ResultsA total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group.ConclusionsAmong patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.).Copyright © 2021 Massachusetts Medical Society.

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