An Open-Label Pilot Study to Evaluate the Efficacy of Sildenafil Citrate in Middle-Aged Men With Late-Onset Dysthymia

Abstract

Late onset dysthymic disorder (DD) in middle-aged and elderly men responds poorly to established antidepressants. Previous studies noted an improvement in mood accompanying sildenafil citrate treatment for erectile dysfunction. We sought to evaluate whether sildenafil's mood effects were independent of the effect on erectile function. A 6-week open label study was conducted with 20 male participants, aged 41-60 who were diagnosed with DD and who had normal erectile function. Participants were treated with sildenafil citrate 25 mg per day for 6 weeks. The primary outcome measure was the 21-item Hamilton Depression Rating Scale. Depressive and sexual symptoms were also evaluated using self-report questionnaires. Treatment with sildenafil resulted in a significant reduction in Hamilton Depression Rating Scale mean scores: from 14.61 +/- 3.5 at baseline to 6.39 +/- 5.13 at end of study (F(3,51) = 32.52, p </= 0.001). No changes in sexual functioning were detected. Significant improvement was also noted on the self-report measures of depressive symptoms. Sildenafil citrate might have an antidepressant effect on late onset DD, that is not attributable to improvement in erectile function. Possible explanations for this effect are offered. Larger placebo controlled studies are warranted.

A literature review and case reports series on the use of phosphodiesterase inhibitors in the treatment of female sexual dysfunction

“…More recent studies might suggest that PDE5i themselves have antidepressant effects and thereby may contribute to increased sexual pleasure. 36,37 At first glance, the positive response rate of 50% in our case series of 16 women who received PDE5i for FSD seems no better than chance. However, the original sildenafil study in men with erectile dysfunction 21 demonstrated a placebo response rate of only 25%.…”

A multicenter, double-blind, placebo-controlled study of sildenafil citrate in Canadian men with erectile dysfunction and untreated symptoms of depression, in the absence of major depressive disorder

“…Subsequently, in a small open-label study, Orr et al (2008) reported that sildenafil relieved depressive symptoms in men with dysthymia in the absence of ED, suggesting that sildenafil may have direct antidepressant effects. This may be because of the ability of sildenafil to cross the bloodbrain barrier to affect networks implicated in depression (Zhang et al, 2002) and an association with testosterone stimulation (Saraiva et al, 2009), which has also been linked to MDD .…”

Expectations do not Influence the Response to Phosphosdiesterase Type 5 Inhibitor Therapy for Erectile Dysfunction

“…However, 47.1% of the placebo were not depressed at the end of the study [ 39 ]. Orr et al [ 40 ] observed a positive effect of sildenafil on depressive symptoms independent of changes in EF. They suggested that these could be due to the effects of the drug on the autonomic nervous system or hippocampal neurogenesis.…”