BACKGROUND: Selective serotonin reuptake inhibitors are increasingly used in the long-term treatment of depression. Much of the supporting evidence about the effects of these drugs comes from discontinuation trials, a variant of randomized controlled trials whose design is problematic to interpret. We conducted a systematic review to examine the efficacy and acceptability of long-term therapy with selective serotonin reuptake inhibitors relative to placebo in the treatment of unipolar depression. METHODS: We identified placebo-controlled randomized trials with a treatment duration of at least 6 months by searching MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to update a recently published systematic review. Efficacy was defined in terms of response to treatment (50% improvement in depression score relative to baseline) and remission (score of 7 or below on the Hamilton rating scale for depression). Key secondary outcomes included quality of life, return to work, need for additional treatment and self-harm. Overall acceptability was defined in terms of dropouts for any reason over a course of treatment. RESULTS: Of the 2693 records identified initially, we included 6 randomized controlled trials that met our eligibility criteria. These studies had a moderate risk of bias, had assigned a total of 1299 participants with depression to either treatment or placebo and had followed both groups for 6-8 months. We observed statistically significant improvements in response to treatment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.12-2.48), but not in remission (OR 1.46, 95% CI 0.92-2.32) or acceptability (OR 0.87, 95% CI 0.67-1.14). The effects appeared greater among patients without comorbidities. INTERPRETATION: There is a lack of classic randomized controlled trials of serotonin reuptake inhibitors lasting more than 1 year for the treatment of depression. The results of our systematic review support current recommendations for 6-8 months of antidepressant treatment following initial recovery but provide no guidance for longer treatment.
BACKGROUND: Selective serotonin reuptake inhibitors are increasingly used in the long-term treatment of depression. Much of the supporting evidence about the effects of these drugs comes from discontinuation trials, a variant of randomized controlled trials whose design is problematic to interpret. We conducted a systematic review to examine the efficacy and acceptability of long-term therapy with selective serotonin reuptake inhibitors relative to placebo in the treatment of unipolar depression. METHODS: We identified placebo-controlled randomized trials with a treatment duration of at least 6 months by searching MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to update a recently published systematic review. Efficacy was defined in terms of response to treatment (50% improvement in depression score relative to baseline) and remission (score of 7 or below on the Hamilton rating scale for depression). Key secondary outcomes included quality of life, return to work, need for additional treatment and self-harm. Overall acceptability was defined in terms of dropouts for any reason over a course of treatment. RESULTS: Of the 2693 records identified initially, we included 6 randomized controlled trials that met our eligibility criteria. These studies had a moderate risk of bias, had assigned a total of 1299 participants with depression to either treatment or placebo and had followed both groups for 6-8 months. We observed statistically significant improvements in response to treatment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.12-2.48), but not in remission (OR 1.46, 95% CI 0.92-2.32) or acceptability (OR 0.87, 95% CI 0.67-1.14). The effects appeared greater among patients without comorbidities. INTERPRETATION: There is a lack of classic randomized controlled trials of serotonin reuptake inhibitors lasting more than 1 year for the treatment of depression. The results of our systematic review support current recommendations for 6-8 months of antidepressant treatment following initial recovery but provide no guidance for longer treatment.
Authors: Michael J Detke; Curtis G Wiltse; Craig H Mallinckrodt; Robert K McNamara; Mark A Demitrack; Istvan Bitter Journal: Eur Neuropsychopharmacol Date: 2004-12 Impact factor: 4.600
Authors: Jeffery A Lieberman; Joel Greenhouse; Robert M Hamer; K Ranga Krishnan; Charles B Nemeroff; David V Sheehan; Michael E Thase; Martin B Keller Journal: Neuropsychopharmacology Date: 2005-03 Impact factor: 7.853
Authors: Welmoed E E Meijer; E R Heerdink; Hubert G M Leufkens; Ron M C Herings; Antoine C G Egberts; Willem A Nolen Journal: Eur J Clin Pharmacol Date: 2004-02-19 Impact factor: 2.953
Authors: Alexander C Tsai; Dan H Karasic; Gwendolyn P Hammer; Edwin D Charlebois; Kathy Ragland; Andrew R Moss; James L Sorensen; James W Dilley; David R Bangsberg Journal: Am J Public Health Date: 2012-06-21 Impact factor: 9.308
Authors: Alastair J Flint; Barnett S Meyers; Anthony J Rothschild; Ellen M Whyte; George S Alexopoulos; Matthew V Rudorfer; Patricia Marino; Samprit Banerjee; Cristina D Pollari; Yiyuan Wu; Aristotle N Voineskos; Benoit H Mulsant Journal: JAMA Date: 2019-08-20 Impact factor: 56.272