Reemergence of sexual dysfunction in patients with major depressive disorder: double-blind comparison of nefazodone and sertraline. Efficacy and tolerability of tadalafil for treatment of erectile dysfunction in men taking serotonin reuptake inhibitors. Triple-blind, placebo-controlled trial of Ginkgo biloba in sexual dysfunction due to antidepressant drugs. Female sexual dysfunction associated with antidepressant administration: a randomized, placebo-controlled study of pharmacologic intervention. Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial. A placebo-controlled, randomized, double-blind study of adjunctive bupropion sustained release in the treatment of SSRI-induced sexual dysfunction. Sustained-release bupropion for selective serotonin reuptake inhibitor-induced sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel-group study. A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction. Bethanecol chloride for treatment of clomipramine-induced orgasmic dysfunction in males. Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial. A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI-induced sexual dysfunction. A placebo-controlled, double-blind trial of Ginkgo biloba for antidepressant-induced sexual dysfunction. A pilot randomized, double-blind, placebo-controlled study of granisetron in the treatment of sexual dysfunction in women associated with antidepressant use. The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study. Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study. Selective serotonin re-uptake inhibitor treatment-emergent sexual dysfunction: randomized double-blind placebo-controlled parallel-group fixed-dose study of a potential adjuvant compound, VML-670. A placebo-controlled, crossover trial of granisetron in SRI-induced sexual dysfunction. Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial. A randomized, placebo-controlled, crossover study of ephedrine for SSRI-induced female sexual dysfunction. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial.
Several different classes of antidepressants have been associated with sexual adverse effects. This double-blind, randomized trial compared the effects of nefazodone and sertraline on reemergence of sexual dysfunction in depressed patients who had experienced sexual dysfunction as a result of sertraline treatment. Depressive symptoms were also monitored.
                One hundred five patients with DSM-III-R major depressive episode who were experiencing sexual dysfunction attributable to sertraline (100 mg/day) were screened for entry. Eligible patients entered a 1-week washout period that was followed by a 7- to 10-day single-blind placebo phase. Patients without symptoms of sexual dysfunction at the end of the single-blind placebo phase were randomly assigned to receive double-blind treatment with either nefazodone (400 mg/day) or sertraline (100 mg/day) for 8 weeks.
                Nearly 3 times more sertraline-treated patients (76%; 25/33) experienced reemergence of sexual dysfunction (ejaculatory and/or orgasmic difficulty) than did nefazodone-treated patients (26%; 10/39) (p < .001). In addition, patients treated with nefazodone were more satisfied with their sexual functioning than were patients treated with sertraline. Both treatment groups demonstrated a similar and sustained improvement in depressive symptoms. Both drugs were well tolerated, and the overall incidence of adverse reactions was similar for both treatment groups; however, 9 sertraline-treated patients (26%) discontinued because of adverse events compared with 5 nefazodone-treated patients (12%). Of the patients discontinuing therapy for adverse events, 5 of the sertraline-treated patients did so because of sexual dysfunction reported as an adverse event, whereas only 1 of the nefazodone-treated patients discontinued therapy secondary to sexual dysfunction.
                In this sample of patients with major depression who had recovered from sexual dysfunction induced by treatment with sertraline, nefazodone treatment resulted in significantly less reemergence of sexual dysfunction than did renewed treatment with sertraline and provided continued antidepressant activity. To evaluate the efficacy and safety of tadalafil in men with treatment-emergent sexual dysfunction due to serotonin reuptake inhibitors.
                The present prospective, double-blind, 12-week study, randomized in a 1:1 ratio to tadalafil 20 mg or placebo taken on demand, included 50 men. The efficacy measures were the changes in total and domain scores of the International Index of Erectile Function questionnaire, Sexual Encounter Profile diary questions 2-6, and the Global Assessment questions (GAQs) 1 and 2. The safety analyses included the evaluation of adverse events, vital signs, serum chemistry results, and electrocardiography findings.
                For the patients who took tadalafil 20 mg, the net median score change from baseline to the endpoint compared with placebo was 26 for the 15-item International Index of Erectile Function; 10, 4, 4, 3, and 3 for the erectile function, intercourse satisfaction, overall satisfaction, orgasmic function, and sexual desire domains; and 3 and 5 points for "yes" responses to the Sexual Encounter Profile 2 and Sexual Encounter Profile 3 questions, respectively. All comparisons between tadalafil and placebo were significant (P < .001). At the endpoint, 92% of the tadalafil group responded affirmatively to both GAQs 1 and 2 compared with 8% of the placebo group (P < .001, for each). In the safety measures, no clinically significant changes attributable to tadalafil use were found.
                Tadalafil 20-mg treatment significantly improved sexual function in patients who were taking serotonin reuptake inhibitors for depression, with mild to moderate, well-tolerable adverse events.
                Copyright © 2011 Elsevier Inc. All rights reserved. A triple-blind (investigator, patient, statistician), randomized, placebo-controlled, trial of Ginkgo biloba 240 mg daily was carried out. Following a 1-week control, it was given to 24 patients with sexual impairment due to antidepressant drugs. Efficacy analysis was carried out on eight males and five females on placebo and six males and five females on Ginkgo, completing the full 12 weeks of treatment. Not included were three subjects who dropped out after 6 weeks. A validated, sex (gender)-orientated questionnaire was recorded at - 1, 0, 1, 3, 6, 9 and 12 weeks, and a non-blind follow-up for a further 6-weeks on Ginkgo. Hamilton anxiety and depression ratings were made at 0, 6 and 12 weeks and simple global assessments of alertness and memory. There were some spectacular individual responses in both groups, but no statistically significant differences, and no differences in side-effects.
                2004 John Wiley & Sons, Ltd. Few controlled trials of pharmacologic intervention in women with antidepressant-associated sexual dysfunction have been reported, and there is uncertainty about the usefulness of putative treatments and the assessment methodologies. The authors evaluated the efficacy of buspirone and amantadine in the treatment of sexual dysfunction associated with fluoxetine administration.
                Women who had been successfully treated with fluoxetine for at least 8 weeks and who had reported a deterioration in sexual function not present before the initiation of fluoxetine entered a 4-week assessment period. After assessment they were randomly assigned to an 8-week treatment trial with buspirone (N=19), amantadine (N=18), or placebo (N=20). Outcomes were assessed by using a patient-rated daily diary and a clinician-rated structured interview.
                While the amantadine-treated women did report significantly greater improvements in energy levels than women in the placebo group, all treatment groups experienced improvement in overall sexual function as well as in most individual measures. There were no statistically significant differences among the three groups.
                Neither buspirone nor amantadine was more effective than placebo in ameliorating antidepressant-associated sexual dysfunction. All groups experienced marked nonspecific improvement during treatment, which suggests the importance of placebo-controlled trials for this condition. Many agents have been proposed as potential treatments for SSRI-associated sexual dysfunction, but few placebo-controlled trials have been reported.
                After a 1-month baseline evaluation, pre-menopausal women with moderate to severe sexual dysfunction associated with the institution of fluoxetine therapy were randomized to augmentation therapy with placebo (N=39), mirtazapine (N=36), yohimbine (N=35) or olanzapine (N=38) for a 6-week period. Outcomes were measured using a daily diary, a biweekly self-report assessment, and a computer assisted structured interview.
                At baseline, orgasm was most severely impaired. After 6 weeks, there was statistically significant improvement on most measures for the overall group of patients, however there were few differences between treatment groups. Isolated treatment differences were observed for the patient self-report of overall sexual function (olanzapine superior to placebo) and the structured interview sexual satisfaction item (mirtazapine inferior to placebo).
                No drug assessed was consistently associated with differences from placebo. The results of the study do not support uncontrolled reports of efficacy for these agents in premenopausal women. Sexual side effects are among the common reasons patients discontinue selective serotonin reuptake inhibitors (SSRIs). While many antidotes have been proposed, few have been subjected to double-blind trials. Some evidence has suggested that bupropion may be an effective antidote for SSRI-induced sexual dysfunction. In this double-blind trial, the efficacy of a standard dose of bupropion sustained release (SR) is evaluated in the treatment of SSRI-induced sexual dysfunction.
                Patients with a history of SSRI-induced sexual side effects were randomly assigned to adjunctive treatment with either bupropion SR 150 mg daily or placebo for 6 weeks. Assessments of sexual function and interest included the Arizona Sexual Experiences Scale (ASEX), Brief Index of Sexual Functioning, and a 10-point visual analogue scale. Efficacy was defined as a 50% improvement on the ASEX at the end of 6 weeks. Data were collected from January 1999 to March 2001.
                Forty-one patients entered the study and completed the 6-week trial. No significant differences were seen between placebo and bupropion SR on the ASEX or on any measure of sexual functioning at the end of the trial.
                A fixed dose of 150 mg/day of bupropion SR taken in the morning does not appear to be effective in the treatment of SSRI-induced sexual dysfunction. Additional trials will be required to define what role, if any, bupropion might have in the treatment of SSRI-induced sexual side effects. The authors compared low-dose sustained-release bupropion with placebo for sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRIs).
                Thirty adults who had received SSRIs for at least 6 weeks, who were euthymic, and who had sexual dysfunction as determined by a total score greater than 19 out of a possible 30 on the Arizona Sexual Experience Scale were randomly assigned to receive either 150 mg/day of sustained-release bupropion or placebo at 6:00 p.m. for 3 weeks.
                There were no significant differences between the sustained-release bupropion and placebo groups as measured by change in Arizona Sexual Experiences Scale or Hamilton Depression Rating Scale scores or side effects.
                Future studies should compare higher doses of bupropion for treating sexual dysfunction and should include a greater number of subjects. This study reports the results of a placebo-controlled, double-blind comparison of bupropion sustained release (SR) as an antidote for sexual dysfunction versus placebo in 42 patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. Exploratory analyses of the association of testosterone and sexual functioning in women in the study were also performed.
                Patients with DSM-IV major depression who experienced a therapeutic response to any SSRI and were experiencing medication-induced global or phase-specific sexual dysfunction, as measured by the Changes in Sexual Functioning Questionnaire (CSFQ), were randomly assigned to receive either bupropion SR 150 mg b.i.d. or placebo for 4 weeks in addition to the SSRI. Total testosterone levels were assessed at baseline and week 4.
                The difference in global sexual functioning, based on the total CSFQ score, was not statistically significant between the 2 groups at week 4, nor were differences in orgasm, desire/ interest as measured by sexual thoughts, or self-reported arousal. There was a statistically significant difference between the 2 groups at week 4 in desire as measured by self-report feelings of desire and frequency of sexual activity. Desire/ frequency showed a significantly greater improvement among those patients receiving bupropion SR compared with placebo (Wilk's F = 5.47, df = 1, p =.024). Frequency was significantly correlated to total testosterone level at baseline (r = 0.36, p =.027) and at week 4 (r = 0.41, p =.025).
                Bupropion SR, as an effective antidote to SSRI-induced sexual dysfunction, produced an increase in desire to engage in sexual activity and frequency of engaging in sexual activity compared with placebo. A larger study is needed to further investigate this finding. To investigate whether bethanecol chloride may be an alternative for the clinical management of clomipramine-induced orgasmic dysfunction, reported to occur in up to 96% of male users.
                In this study, 12 fully remitted panic disorder patients, complaining of severe clomipramine-induced ejaculatory delay, were randomly assigned to either bethanecol chloride tablets (20 mg, as needed) or placebo in a randomized, double-blind, placebo-controlled, two-period crossover study. A visual analog scale was used to assess severity of the orgasmic dysfunction.
                A clear improvement was observed in the active treatment period. No placebo or carry-over effects were observed.
                These findings suggest that bethanecol chloride given 45 minutes before sexual intercourse may be useful for clomipramine-induced orgasmic dysfunction in males. Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance.
                To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants.
                Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment.
                Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks.
                The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D).
                Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration.
                In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment. We sought to determine whether maca, a Peruvian plant, is effective for selective-serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. We conducted a double-blind, randomized, parallel group dose-finding pilot study comparing a low-dose (1.5 g/day) to a high-dose (3.0 g/day) maca regimen in 20 remitted depressed outpatients (mean age 36+/-13 years; 17 women) with SSRI-induced sexual dysfunction. The Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) were used to measure sexual dysfunction. Ten subjects completed the study, and 16 subjects (9 on 3.0 g/day; 7 on 1.5 g/day) were eligible for intent-to-treat (ITT) analyses on the basis of having had at least one postbaseline visit. ITT subjects on 3.0 g/day maca had a significant improvement in ASEX (from 22.8+/-3.8 to 16.9+/-6.2; z=-2.20, P=0.028) and in MGH-SFQ scores (from 24.1+/-1.9 to 17.0+/-5.7; z=-2.39, P=0.017), but subjects on 1.5 g/day maca did not. Libido improved significantly (P<0.05) for the ITT and completer groups based on ASEX item #1, but not by dosing groups. Maca was well tolerated. Maca root may alleviate SSRI-induced sexual dysfunction, and there may be a dose-related effect. Maca may also have a beneficial effect on libido. The aim of this study was to examine the effect of Ginkgo biloba on antidepressant-induced sexual dysfunction. The Ginkgo biloba (n=19) and the placebo groups (n=18) were divided; each to be administered with Ginkgo biloba and placebo respectively for 2 months by means of a randomized placebo-controlled, double-blind study. The results of this 2 month trial were: (1) there was no statistical significant difference from the placebo at weeks 2, 4 and 8 after medication; (2) in comparison with baseline, both the Ginkgo biloba group and the placebo group showed improvement in some part of the sexual function, which is suggestive of the importance of the placebo effect in assessing sexual function. This study did not replicate a prior positive finding supporting the use of Ginkgo biloba for antidepressant, especially SSRI, induced sexual dysfunction.
                Copyright 2002 John Wiley & Sons, Ltd. A pilot study was conducted to evaluate the usefulness of granisetron for the treatment of antidepressant induced sexual dysfunction in women. Twelve women with antidepressant induced sexual dysfunction (AISD) were assigned granisetron (n=5) or placebo (n=7) in a 14-day randomized, double-blind, placebo-controlled study. One participant in the granisetron group did not complete the study. Participants were assessed at baseline, day 7 and day 14 using the Feiger Sexual Function and Satisfaction Questionnaire and the Arizona Sexual Experience Scale. No statistical differences were measured at baseline or at endpoint between the granisetron or placebo group. This study did not produce evidence supporting the usefulness of granisetron in AISD. To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined.
                The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period.
                After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age.
                Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion. A significant number of patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) report sexual dysfunction. SSRI-induced sexual dysfunction adversely affects quality of life and patient adherence to and compliance with treatment regimens. This trial examined the efficacy and safety of adjunctive bupropion in the treatment of SSRI-induced female sexual dysfunction. Sexual function was assessed by using the sexual function domains of the Female Sexual Function Index (primary efficacy outcome measure) and the Clinical Global Impression Scale adapted for sexual function (secondary efficacy outcome measure). End point treatment satisfaction was assessed using a Visual Analog Scale. A total of 218 women (25-45 years old) with SSRI-induced sexual dysfunction were randomized to receive 12 weeks of double-blind fixed dosed treatment with bupropion sustained release 150 mg b.i.d. (n = 109) or placebo (n = 109). The mean (SD) for Female Sexual Function Index total score was higher in the bupropion sustained release group (25.9 (5.12), 95% confidence interval (CI) 22.2-29.4) than in the placebo group (17.2 (4.9), 95% CI 15.8-20.1) (p = 0.001). Mean (SD) Clinical Global Impression Scale score for the bupropion group (2.4 (0.6), 95% CI 2.0-3.6) was significantly lower than that for the placebo group (4.2 (0.8), 95% CI 3.4-5.4) (p = 0.001). At the end of the trial the mean (SD) scores for desire (4.1 (0.7), 95% CI 3.5-4.8) (p = 0.001), arousal (4.4 (0.6), 95% CI 3.7-4.8) (p = 0.01), lubrication (4.4 (0.4), 95% CI 3.3-4.8) (p = 0.001), orgasm (4.4 (0.5), 95% CI 3.7-4.7) (p = 0.001), and satisfaction (4.2 (0.7), 95% CI 3.4-4.8) (p = 0.001) were significantly higher in the bupropion group. The highest improvement was observed in sexual desire, followed by lubrication. Compared with baseline, desire and lubrication domains increased by 86.4% (95% CI 64.9-102.2%, p = 0.001) and 69.2% (95% CI 44.7-82.6%, p = 0.001) in the bupropion group. Adjunctive treatment with bupropion sustained release during a 12-week period significantly improved key aspects of sexual function in women with SSRI-induced sexual dysfunction. Sexual dysfunction is common during acute and continuation treatment of depressed patients with selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibitors (ssRIs), but there is no consensus on clinical management. Compounds with 5-HT(1A) agonist properties have been proposed as adjuvant agents in patients continuing with ssRIs. Randomized double-blind placebo-controlled parallel-group fixed-dose 4-week treatment study. Previously depressed male or female patients in symptomatic remission receiving stable doses of fluoxetine or paroxetine but experiencing treatment-emergent sexual dysfunction were randomised to double-blind treatment with placebo or VML-670 (a 5-HT(1A) and 5-HT(1D) agonist). sexual dysfunction was assessed by the Arizona sexual Experiences scale (ASEX). Two-hundred and eighty-eight patients (204 women, 84 men; mean age 44.2 years) received VML-670 (n = 149; 107 women, 42 men) or placebo (n = 139; 97 women, 42 men). In the intention-to-treat, last-observation carried forward analysis (n = 282), proportionately more patients became free of sexual dysfunction with VML-670 (34.3% versus 27.9% with placebo) but this difference was not statistically significant. Male patients treated with VML-670 showed a significantly greater (p =0.01) improvement in ability to achieve and maintain penile erection (a secondary outcome measure). A similar proportion of patients reported on-treatment, treatment-emergent adverse events with VML-670 (71.1%) and placebo (68.3%), and a similar proportion experienced at least one treatment-related adverse event (36.9% versus 35.3%). Double-blind treatment with VML-670 offered no significant advantage over placebo on the primary outcome measure in the overall sample. Further studies may be warranted in larger groups of male patients with sexual dysfunction. Sexual side effects are commonly associated with serotonin reuptake inhibitor (SRI) therapy. The mechanism underlying SRI-induced sexual dysfunction has been hypothesized to be mediated by direct serotonergic effects. Evidence from open-label reports suggests that cyproheptadine, nefazodone, mirtazapine, and mianserin, which block one or more serotonin receptors, may reverse sexual side effects. The current study was a prospective, randomized, crossover trial comparing granisetron, a serotonin-3 antagonist, with placebo in outpatients who developed sexual dysfunction during SRI treatment.
                Thirty-one outpatients who were currently experiencing sexual dysfunction associated with SRIs were randomly assigned to double-blind treatment with granisetron (1-1.5 mg) or placebo for use 1 to 2 hours prior to sexual activity. Patients rated sexual symptoms after each trial using the Sexual Side Effect Scale (SSES). After 4 trials of the medication, patients crossed over to the other treatment for 4 more trials.
                Twenty patients received at least 1 dose of placebo and granisetron. Analysis by repeated-measures analysis of variance showed no significant effects of granisetron relative to placebo. Significant improvement between baseline and treatment-phase SSES scores was observed for both granisetron (p = .0004) and placebo (p = .0081). The study medication was generally well tolerated.
                The results of this study do not support the efficacy of granisetron (1-2 mg) in the treatment of SRI-associated sexual side effects. A significant placebo response may be associated with the treatment of SRI-induced sexual dysfunction. To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED).
                Men (aged>or=18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event log of sexual activity.
                Patients receiving sildenafil (N=71) versus placebo (N=71) reported significantly higher mean+/-SE scores on Q3 (3.9+/-0.2 vs. 3.1+/-0.2, p=.003) and Q4 (3.7+/-0.2 vs. 2.8+/-0.2, p<.001) of the IIEF and significantly higher scores on all domains of the IIEF. Patients receiving sildenafil also reported significantly improved scores on all questions of the EDITS questionnaire (p<.02) and the GEQ (p<.0001) and an increased number of successful sexual intercourse attempts per week (p<.0001) compared with patients receiving placebo. All patients remained in MDD remission (score<or=10 on the Hamilton Rating Scale for Depression). Adverse events in patients taking sildenafil (vs. placebo) were headache (9% vs. 9%), dyspepsia (9% vs. 1%), anxiety (6% vs. 4%), and abnormal vision (3% vs. 0%).
                Short-term (6-week) administration of sildenafil was well tolerated and significantly improved erectile function and overall sexual satisfaction in men with ED associated with SRI therapy for MDD. Sildenafil may be successfully used to treat SRI-associated ED without interruption of antidepressant therapy. The objective of this study was to determine whether ephedrine, an alpha- and beta-adrenergic agonist previously shown to enhance genital blood flow in women, has beneficial effects in reversing antidepressant-induced sexual dysfunction. Nineteen sexually dysfunctional women receiving either fluoxetine, sertraline, or paroxetine participated in an eight-week, double-blind, placebo-controlled, cross-over study of the effects of ephedrine (50 mg) on self-report measures of sexual desire, arousal, orgasm, and sexual satisfaction. Although there were significant improvements relative to baseline in sexual desire and orgasm intensity/pleasure on 50 mg ephedrine 1-hr prior to sexual activity, significant improvements in these measures, as well as in sexual arousal and orgasmic ability also were noted with placebo. These findings highlight the importance of conducting placebo-controlled trials for this condition. Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women.
                To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women.
                An 8-week prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 1, 2003, and January 1, 2007, at 7 US research centers that included 98 previously sexually functioning, premenopausal women (mean [SD] age 37.1 [6] years) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction.
                Forty-nine patients were randomly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity.
                The primary outcome measure was the mean difference in change from baseline to study end (ie, lower ordinal score) on the Clinical Global Impression sexual function scale. Secondary measures included the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale-female version, the University of New Mexico Sexual Function Inventory-female version, a sexual activity event log, and the Hamilton Depression Rating scale. Hormone levels were also assessed.
                In an intention-to-treat analysis, women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 (95% confidence interval [CI], 1.6-2.3) compared with those taking placebo (1.1; 95% CI, 0.8-1.5), with a mean end point difference of 0.8 (95% CI, 0.6-1.0; P = .001). Assigning baseline values carried forward to the 22% of patients who prematurely discontinued resulted in a mean end point in the sexual function score of 1.5 (95% CI, 1.1-1.9) among women taking sildenafil compared with 0.9 (95% CI, 0.6-1.3) among women taking placebo with a mean end point difference of 0.6 (95% CI, 0.3-0.8; P = .03). Baseline endocrine levels were within normal limits and did not differ between groups. The mean (SD) Hamilton scores for depression remained consistent with remission in both groups (4.0 [3.6]; P = .90). Headache, flushing, and dyspepsia were reported frequently during treatment, but no patients withdrew because of serious adverse effects.
                In this study population, sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects.
                clinicaltrials.gov Identifier: NCT00375297.
The evidence currently available is rather limited. For men with antidepressant-induced erectile dysfunction, the addition of sildenafil or tadalafil appears to be an effective strategy. For women with antidepressant-induced sexual dysfunction the addition of bupropion at higher doses appears to be the most promising approach studied so far.