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Introduction: Vilazodone is a potent serotonin (5-HT) reuptake inhibitor and 5-HT₁A receptor partial agonist approved by the US Food and Drug Administration for the treatment of major depressive disorder (MDD) in adults. This study evaluated the efficacy and tolerability of vilazodone in the treatment of MDD., Method: This 8-week, randomized (1:1), double-blind, placebo-controlled, parallel-group, fixed-dose study conducted from January 2012 to February 2013 compared vilazodone 40 mg/d with placebo in outpatients with DSM-IV-TR-diagnosed MDD. The primary efficacy measure was Montgomery-Asberg Depression Rating Scale (MADRS) total score change from baseline to week 8 analyzed by a mixed-effects model for repeated measures on the intent-to-treat population (placebo = 252, vilazodone = 253). Secondary efficacy outcomes were Clinical Global Impressions-Severity of Illness (CGI-S) Scale score change from baseline and MADRS sustained response rate (total score ≤ 12 for at least the last 2 consecutive double-blind visits)., Results: Approximately 83% of patients completed the study. Least squares mean differences (95% CI) were statistically significant for vilazodone versus placebo on MADRS (-5.117 [-6.886 to -3.347], P < .00001) and CGI-S (-0.622 [-0.845 to -0.399], P < .00001) change from baseline; statistically significant improvements versus placebo occurred at week 2 and persisted for the study duration. The MADRS sustained response rate was 17% for placebo and 27% for vilazodone (P < .01). Patients taking vilazodone versus placebo had higher rates of diarrhea and nausea; most incidences were mild in severity. Weight increase and sexual dysfunction adverse events were low in both groups., Conclusions: A large and significant treatment effect on the MADRS and statistically significant improvement on the CGI-S demonstrated meaningful depressive symptom improvements. Vilazodone was generally well tolerated., Trial Registration: ClinicalTrials.gov identifier: NCT01473394., (© Copyright 2014 Physicians Postgraduate Press, Inc.)

Objective: To compare the effects on sexual functioning and the antidepressant efficacy of once-daily bupropion extended release (XL) and escitalopram in adults with major depressive disorder (MDD)., Method: Adult outpatients with moderate to severe DSM-IV-defined MDD and normal sexual functioning were randomly assigned to receive bupropion XL (300-450 mg/day; N = 276), escitalopram (10-20 mg/day; N = 281), or placebo (N = 273) for up to 8 weeks in 2 identically designed, randomized, double-blind, parallel-group studies (study 1 conducted from February 6, 2003, to June 10, 2004; study 2 conducted from January 21, 2003, to June 15, 2004). Data were analyzed prospectively for each study individually, and pooled data were analyzed retrospectively., Results: In both the individual studies and the pooled dataset, the incidence of orgasm dysfunction at week 8 (primary endpoint) and the incidence of worsened sexual functioning at the end of the treatment period were statistically significantly lower with bupropion XL than with escitalopram (p < .05), not statistically different between bupropion XL and placebo (p > or = .067), and statistically significantly higher with escitalopram than with placebo (p < or = .001). The percentages of patients with orgasm dysfunction at week 8 in study 1, study 2, and the pooled dataset, respectively, were 13%, 16%, and 15% with bupropion XL; 32%, 29%, and 30% with escitalopram; and 11%, 8%, and 9% with placebo. The respective percentages of patients with worsened sexual functioning at the end of the treatment period were 18%, 22%, and 20% with bupropion XL; 37%, 34%, and 36% with escitalopram; and 14%, 16%, and 15% with placebo. Mean changes in Changes in Sexual Functioning Questionnaire scores for all domains at week 8 were statistically significantly worse for escitalopram compared with bupropion XL (p < or = .05). Separation from placebo could not be established at a statistical .05 level for bupropion on 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. However, escitalopram showed statistical superiority to placebo on HAM-D-17 total score in one of the 2 studies and in the pooled data. Bupropion XL did not statistically differ from escitalopram with respect to mean change in HAM-D-17 total score, HAM-D-17 response or remission rates, percentage of patients much or very much improved on Clinical Global Impressions-Improvement scale scores, or mean changes in the Hospital Anxiety and Depression (HAD) scale total score or Clinical Global Impressions-Severity of Illness scale score at week 8., Conclusions: Bupropion XL had a sexual tolerability profile significantly better than that of escitalopram with similar HAM-D-17 remission rates and HAD total scores in patients with MDD.

The ideal antidepressant would control depression with no adverse effect on sexual function. Erectile dysfunction and other sexual dysfunction associated with antidepressant medication treatment are problems with many antidepressants and can lead to patient dissatisfaction and decreased compliance with treatment. A computerized MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sexual dysfunction. Emphasis was placed on studies with specific sexual function measurements taken before and after treatment and placebo control. Mixed mediator, nonserotonergic antidepressants that block postsynaptic serotonin type 2 receptors (nefazodone, mirtazapine) or that primarily increase dopamine or norepinephrine levels (bupropion) were thought to be good choices for avoiding antidepressant-associated sexual dysfunction or for switching patients in whom antidepressant-associated sexual dysfunction emerged. Comparisons with serotonin reuptake inhibitors (SRIs) have revealed less desire and orgasm dysfunction with nonserotonergic bupropion, less orgasm dysfunction with nefazodone, and superior overall satisfaction with sexual functioning with bupropion or nefazodone. However, most of these studies have design flaws that make evidence-based claims of efficacy difficult to substantiate. Agents proposed for antidote use in antidepressant-associated sexual dysfunction have either not been studied in men or not proved efficacious in randomized placebo-controlled trials. Switching to and augmentation with bupropion or nefazodone have also not clearly shown efficacy in controlled trials and require care and monitoring to avoid SRI discontinuation symptoms and loss of antidepressant efficacy. Few proposed treatment options, apart from avoidance, have proved effective for antidepressant-associated sexual dysfunction, which can have negative consequences on depression management.

Background: Sexual dysfunction commonly occurs during antidepressant treatment. However, the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature. The objectives of this study were (1) to estimate the prevalence of sexual dysfunction among patients taking newer antidepressants (bupropion immediate release [IR], bupropion sustained release [SR], citalopram, fluoxetine, mirtazapine, nefazodone, paroxetine, sertraline, venlafaxine, and venlafaxine extended release [XR]) and (2) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction., Method: This cross-sectional, observational study was conducted in 1101 U.S. primary care clinics. Adult outpatients (4534 women and 1763 men) receiving antidepressant monotherapy were enrolled. The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Questionnaire., Results: In the overall population, bupropion IR (22%) and SR (25%) and nefazodone (28%) were associated with the lowest risk for sexual dysfunction, whereas selective serotonin reuptake inhibitor (SSRI) antidepressants, mirtazapine, and venlafaxine XR were associated with higher rates (36%-43%). In a prospectively defined subpopulation unlikely to have predisposing factors for sexual dysfunction, the prevalence of sexual dysfunction ranged from 7% to 30%, with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR. Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction., Conclusion: Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a validated rating scale. Overall, SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone. Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians, greater recognition and education are imperative when prescribing antidepressant treatment.