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Comparative Risk for Harms of Second-Generation Antidepressants: A Systematic Review and Meta-Analysis
Abstract
Background Evidence indicates that only minor differences in efficacy exist among second-generation antidepressants for the treatment of major depressive disorder (MDD). However, a comprehensive assessment of both benefits and harms is crucial to evaluate the net benefit.Objective To review systematically the comparative harms of second-generation antidepressants for the treatment of MDD in adults by including both experimental and observational evidence.Data sources We searched MEDLINE, EMBASE, PsychLit, The Cochrane Library and the International Pharmaceutical Abstracts from 1980 to April 2007. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database to identify unpublished research.Study selection Eligible study designs were trials and observational studies comparing one drug of interest with another.Data extraction Two persons independently reviewed abstracts and full-text articles. One investigator extracted relevant data. A senior reviewer checked data for completeness and accuracy.Data synthesis We included 104 experimental and observational studies. If data were sufficient, we conducted meta-analyses of randomized controlled trials on the relative risk of specific adverse events. Findings indicate that the spectrum of adverse events is similar. The frequency of specific adverse events, however, differed across drugs. Venlafaxine was associated with a significantly higher rate of nausea and vomiting than selective serotonin reuptake inhibitors. Compared with other drugs, paroxetine frequently led to more sexual adverse effects and bupropion to fewer such effects; mirtazapine and paroxetine was associated with more weight gain and sertraline with a higher rate of diarrhoea. Overall, however, these differences did not lead to different discontinuation rates. The evidence is insufficient to draw conclusions about rare but severe adverse events.Conclusions Adverse event profiles are similar among second-generation antidepressants. However, different frequencies of specific adverse events might be clinically relevant and influence the choice of a treatment.
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“around 60% of patients using second-generation antidepressants, such as selective serotonin reuptake inhibitors [SSRIs] encountered adverse events, and 7% to 15% quit treatment due to the events (Gartlehner et al. 2008)”
From A Scoping Review of Correctional-Based Interventions for Women Prisoners with Mental Health Problems (2023) · cites this paper as Gartlehner et al. 2008
In the citing paper
“A meta-analysis further showed that the relative risk of nausea and vomiting for venlafaxine was higher than those for SSRIs with RR of 1.53 (95% CI, 1.26–1.86).44”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [44]
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Metadata
- Authors
- Gartlehner, G., Thieda, P., Hansen, R. A., Gaynes, B. N., DeVeaugh-Geiss, A., Krebs, E. E., & Lohr, K. N.
- Affiliations
- Universität für Weiterbildung Krems (AT)
- University of North Carolina at Chapel Hill (US)
- Regenstrief Institute (US)
- RTI International (US)
- Corresponding author
- Gartlehner, Gerald
- Venue
- Drug Safety
- Published
- 2008
- Volume
- 31
- Issue
- 10
- Pages
- 851-865
- ISSN
- 0114-5916 (ISSN-L)
- OpenAlex
- W2006078781
- Cited by
- 150
- References
- 141
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 9 · 2015: 10 · 2014: 7 · 2013: 11 · 2012: 10
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Safety (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (290-02-0016)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- second-generation antidepressants, major depressive disorder, adverse drug reactions, drug safety comparison, venlafaxine, selective serotonin reuptake inhibitors, paroxetine, bupropion, mirtazapine, sertraline, sexual adverse effects, weight gain, nausea and vomiting, diarrhea, discontinuation rate, net benefit
- MeSH terms
- Adult, Blood Pressure, Depressive Disorder, Major, Major Depressive Disorder, Humans, Nausea, Seizures, Sexual Dysfunction, Physiological, Vomiting, Treatment Outcome, Risk Assessment, Antidepressive Agents, Second-Generation, Sexual Dysfunctions, Psychological
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