Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials
Open accessAbstract
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.
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- Authors
- Deshauer, D., Moher, D., Fergusson, D., Moher, E., Sampson, M., & Grimshaw, J.
- Affiliations
- University of Waterloo (CA)
- University of Ottawa (CA)
- Corresponding author
- Deshauer, D.
- Venue
- Canadian Medical Association Journal
- Publisher
- CMA Joule Inc.
- Published
- 2008-05-06
- Volume
- 178
- Issue
- 10
- Pages
- 1293-1301
- ISSN
- 0820-3946 (ISSN-L)
- 1488-2329
- PMC
- PMC2335186
- OpenAlex
- W2156078023
- Cited by
- 78
- References
- 45
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 6 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Canadian Medical Association Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Ottawa
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Keywords
- selective serotonin reuptake inhibitors, major depressive disorder, long-term antidepressant treatment, treatment response, remission, treatment acceptability, dropout, quality of life, return to work, comorbidities
- MeSH terms
- Depressive Disorder, Humans, Placebos, Quality of Life, Research Design, Randomized Controlled Trials as Topic, Outcome Assessment, Health Care, Selective Serotonin Reuptake Inhibitors
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