Drug Safety

, Volume 37, Issue 1, pp 19–31 | Cite as

Sexual Dysfunction associated with Second-Generation Antidepressants in Patients with Major Depressive Disorder: Results from a Systematic Review with Network Meta-Analysis

  • Ursula ReichenpfaderEmail author
  • Gerald Gartlehner
  • Laura C. Morgan
  • Amy Greenblatt
  • Barbara Nussbaumer
  • Richard A. Hansen
  • Megan Van Noord
  • Linda Lux
  • Bradley N. Gaynes
Systematic Review



Sexual dysfunction (SD) is prevalent in patients with major depressive disorder (MDD) and is also associated with second-generation antidepressants (SGADs) that are commonly used to treat the condition. Evidence indicates under-reporting of SD in efficacy studies. SD associated with antidepressant treatment is a serious side effect that may lead to early termination of treatment and worsening of quality of life.


Our objective was to systematically assess the harms of SD associated with SGADs in adult patients with MDD by drug type.


We retrieved English-language abstracts from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012 as well as from reference lists of pertinent review articles and grey literature searches. Two independent reviewers identified randomized controlled trials (RCTs) of at least 6 weeks’ duration and observational studies with at least 1,000 participants.

Study Selection

Reviewers abstracted data on study design, conduct, participants, interventions, outcomes and method of SD ascertainment, and rated risk of bias. A senior reviewer checked and confirmed extracted data and risk-of-bias ratings.


Random effects network meta-analysis using Bayesian methods for data from head-to-head trials and placebo-controlled comparisons; descriptive analyses calculating weighted mean rates from individual trials and observational studies.


Data from 63 studies of low and moderate risk of bias (58 RCTs, five observational studies) with more than 26,000 patients treated with SGADs were included. Based on network meta-analyses of 66 pairwise comparisons from 37 RCTs, most comparisons showed a similar risk of SD among included SGADs. However, credible intervals were wide and included differences that would be considered clinically relevant. We observed three main patterns: bupropion had a statistically significantly lower risk of SD than some other SGADs, and both escitalopram and paroxetine showed a statistically significantly higher risk of SD than some other SGADs. We found reporting of harms related to SD inconsistent and insufficient in some trials.


Most trials were conducted in highly selected populations. Search was restricted to English-language only.

Conclusion and Implications

Because of the indirect nature of the comparisons, the often wide credible intervals, and the high variation in magnitude of outcome, we rated the overall strength of evidence with respect to our findings as low. The current degree of evidence does not allow a precise estimate of comparative risk of SD associated with a specific antidepressant. In the absence of such evidence, clinicians need to be aware of SD as a common adverse event and should discuss patients’ preferences before initiating antidepressant therapy.


Major Depressive Disorder Paroxetine Sexual Dysfunction Bupropion Duloxetine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This project was originally funded under Contract No. HHSA-290-2007-10056I from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. The authors of this manuscript are responsible for its content. Statements in the manuscript should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

No sources of funding were used to assist in the preparation of this systematic review. However, this review updates part of a larger comparative effectiveness review on SGAD [19], which was funded by and conducted for the US AHRQ, US Department of Health and Human Services under contract no. HHSA-290-2007-10056I.

Amy Greenblatt has participated in research funded by the US AHRQ during the conduct of the study. Richard Hansen has received consulting fees from Daiichi Sankyo and Novartis for studies on unrelated topics, and has served as an expert witness for Allergan for Botox drug safety. Ursula Reichenpfader, Gerald Gartlehner, Laura C. Morgan, Barbara Nussbaumer, Megan Van Noord, Linda Lux, and Bradley N. Gaynes have no conflicts of interest that are directly relevant to the content of this study.

Network meta-analyses were conducted by Tania Wilkins, PhD (The University of North Carolina at Chapel Hill, Gillings School of Global Public Health Biostatistics, 3101 McGavran-Greenberg Hall, Chapel Hill, NC 27599-7420, USA).

Supplementary material

40264_2013_129_MOESM1_ESM.docx (332 kb)
Supplementary material 1 (DOCX 332 kb)
40264_2013_129_MOESM2_ESM.docx (26 kb)
Supplementary material 2 (DOCX 25 kb)


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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Ursula Reichenpfader
    • 1
    • 5
    Email author
  • Gerald Gartlehner
    • 1
    • 2
  • Laura C. Morgan
    • 2
  • Amy Greenblatt
    • 2
  • Barbara Nussbaumer
    • 1
  • Richard A. Hansen
    • 3
  • Megan Van Noord
    • 1
    • 2
  • Linda Lux
    • 2
  • Bradley N. Gaynes
    • 4
  1. 1.Department for Evidence-based Medicine and Clinical EpidemiologyDanube University KremsKremsAustria
  2. 2.RTI InternationalResearch Triangle ParkUSA
  3. 3.Auburn UniversityAuburnUSA
  4. 4.Department of PsychiatryUniversity of North Carolina School of Medicine Chapel HillChapel HillUSA
  5. 5.Division of Community Medicine, Department of Medical and Health SciencesLinköping UniversityLinköpingSweden

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