There are limited data to indicate effective treatment strategies for antidepressant-related sexual dysfunction, in particular for patients with treatment-resistant major depression. We subanalyzed our published data whether augmentation with methylphenidate extended release (OROS MPH) improved sexual dysfunction associated with antidepressants in patients with treatment-resistant major depression. The primary efficacy measure was the change in Arizona Sexual Experiences Survey (ASEX) from baseline to end of treatment in an intent-to-treat analysis with last observation carried forward approach. There were no significant differences between the 2 groups in terms of changes in ASEX scores over time (F1,35 = 1.14; P = 0.32), although the numerical decrease in ASEX score was greater in OROS MPH (mean change, -4.5; 20.1% decrease) than in the placebo group (mean change, -0.6; 2.6% decrease). Augmentation with OROS MPH showed no statistically significant benefit in antidepressant-related sexual dysfunction, although addition of OROS MPH to antidepressants did not worsen preexisting sexual dysfunction. Adequately powered controlled trials are needed to fully evaluate the efficacy of OROS MPH in this area.