Little differences among antidepressants regarding sexual dysfunction, but bupropion performs best


Antidepressant treatment is associated with a variety of side effects, including emotional changes, weight gain or fatigue. As pharmaceutical treatment has evolved, clinicians have become increasingly aware of another major adverse effect of modern antidepressants: sexual dysfunction.

Current figures estimate that up to every second patient will, at some stage, experience reduced sexual function, which is likely to lead to significant patient strain. However, there is still insufficient knowledge about which drug compares most favourably in terms of sexual side effects, leaving clinicians without coherent prescription guidelines. A recent review by Reichenpfader et al. (2013) aims to close this gap.


The authors screened common medical databases for randomised controlled trials (RCTs) where second-generation antidepressants (including SSRIs like fluoxetine, but also atypical compounds like bupropion or mirtazapine) were used to treat major depression for at least 6 weeks. In total, 37 RCTs and five observational studies with more than 26,000 patients met the inclusion criteria.


When it came to sexual side-effects, this review found it hard to differentiate between the included drugs


  • Among male patients, prevalence of sexual dysfunction during treatment was 12.3% (95%CI, 8.8 to 15.8%)
  • There was insufficient data to calculate values for female patients
  • Across different drugs, sexual dysfunction prevalence varied, ranging in RCTs, e.g.
    • 8.8% for fluoxetine (95% CI, 0.5 to 17%)
    • 15.8% for sertraline (95% CI, 1.2 to 30.4%)
  • Observational studies suggested that bupropion was associated with the lowest occurrence (7%) of sexual dysfunction
  • Overall data quality was poor, including insufficient assessment of sexual side effects


The authors conclude that:

Based on the findings of this review using data from RCTs and observational studies on adverse events and second-generation antidepressant drugs, the comparative risk of sexual dysfunction associated with a specific antidepressant cannot be precisely determined.


There are a few limitations that affect this meta-analysis:

  • Differences in medication schedules, including dosage or concomitant treatment, were not considered and neither were comorbidities (like alcohol abuse) that could have affected sexual function
  • In addition, study duration was usually very short, which makes evaluation of long-term effects impossible and sex-specific effects were not investigated
  • In general, there was significant heterogeneity across primary studies regarding assessment of sexual dysfunction as well as pre-treatment scores
Comorbidities such as alcohol

Comorbidities such as alcohol abuse were not taken into account


While poor data quality prevents straightforward conclusions, this meta-analysis still highlights important points for clinicians:

  • Firstly, the reviewed observational studies suggest buproprion is the drug of choice in terms of maintaining sexual function. This conclusion agrees with its supposed mechanism of action, which is different from compounds associated with higher risks (e.g. sertraline)
  • Secondly, variation among other drugs seems negligible, demanding other consideration when making an informed treatment decision
  • Thirdly, as sexual dysfunction can cause significant emotional and relationship strain, clinicians should keep patient preferences in mind when prescribing an antidepressant
  • Lastly, even though this meta-analysis relies on a significant number of patients (>26,000), the fact that it offers very little methodologically sound conclusions emphasises the need of more research in this area


This meta-analysis suggests that, in spite of sub-optimal data quality, the likelihood of sexual side effects is an important issue when initiating antidepressant treatment. Crucially, clinicians should be aware of some differences between compounds and raise these issues to patients.

GPs will find the data in this review helpful when prescribing antidepressants

GPs will find the data in this review helpful when prescribing antidepressants


Reichenpfader, U., Gartlehner, G., Morgan, L.C., Greenblatt, A., Nussbaumer, Hansen, R.A. et al. (2014). Sexual dysfunction associated with second-generation antidepressants in patients with major depressive disorder: results from a systematic review with network meta-analysis. Drug Saf, 37(1), 19-31. [PubMed abstract] Angst, J. (1998).

Sexual problems in healthy and depressed persons. Int Clin Psychopharmacol13(6), 1-4.  [PubMed abstract]

Share on Facebook Tweet this on Twitter Share on LinkedIn Share on Google+