Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Bupropion as Treatment for Methadone-Emergent Sexual Dysfunction in Men

Abstract

Methadone is largely recognized as an effective treatment for opiate-dependent patients; however, it causes reduced brain dopaminergic action resulting in significant sexual dysfunction. Bupropion is a dopamine reuptake inhibitor which can potentially improve erectile function among male patients on methadone (MMT). This is a phase II, randomized, double-blind, parallel-group, placebo-controlled trial, involving 80 MMT male patients (73.4%) with mean age of 42.83 years ±9.68. These MMT male patients were randomly assigned into two groups to receive bupropion and placebo, respectively. The primary efficacy outcome measure was the difference between the two groups in end-point mean improvement scores using the measurement of Clinical Global Impression Scale adapted for Sexual Function (CGI-SF) at baseline (week 0) and at weeks 2, 4, and 6. Malay version of the sexual desire inventory-2 (SDI-2-BM) and Malay version of International Index of Erectile Function 15 (Mal-IIEF-15) domain scores were evaluated as secondary parameters. Improvement of the end-point mean from baseline were seen across the scores of SDI-2-BM (mean difference = 11.77 ± 2.90, 95% confidence interval (CI) [3.89, 19.54], p < .001) and Mal-IIEF-15 (mean difference = 8.37 ± 2.71, 95% CI [15.75, 0.99], p = .02), and the total plasma testosterone level (mean difference = 4.03, 95% CI [0.90, 7.15], p = .01). A categorical improvement of “much/very much improved” (CGI-SF score = 2) was reported by 58.3% (n = 21/36) of bupropion SR-assigned versus 27.7% (n = 10/36) placebo-assigned patient. Bupropion was well tolerated with no serious adverse events reported other than insomnia (17.7%). Six weeks of bupropion SR treatment reported significant improvement in key aspects of sexual function among male opiate-dependent patients on methadone maintenance treatment with emergent sexual dysfunction.

Cigarette Smoking Is Significantly Linked to Sexual Dissatisfaction in Chinese Heroin-Dependent Patients Receiving Methadone Maintenance Treatment

“…Findings from pharmacological studies have shown that methadone and other opioids could suppress the release of gonadal hormones via its inhibitory effect on HPG axis, including testosterone, which plays a critical role in maintaining sexual desire in both men and women (51–55). Therefore, in the clinical management of heroin addiction, sexual dysfunction is generally considered as one of the most common side effects associated with methadone treatment (25, 56), as confirmed by the significant association between a high dose of methadone and sexual dissatisfaction in Table 3 of the present report.…”

Treatments of Sexual Dysfunction in Opioid Substitution Therapy Patients: A Systematic Review and Meta-Analysis

“…Due to the difference in terms of the pathophysiology of sexual dysfunction, the treatment option of sexual dysfunction in the OST population is different from the other population. Antidepressants such as bupropion and trazodone and herbal alternatives such as rosa Damascena and ginseng have been reported to significantly improve OST patients with sexual dysfunction [8,[22][23][24][25][26][27]. Although various clinical studies and reviews have explored the role of intervention for sexual dysfunction in many conditions, such as diabetes, stroke, and cancer population, the effectiveness and safety of sexual dysfunction intervention in the OST population has not been studied thoroughly [28][29][30].…”

“…• Outcomes: Studies with any mean score of validated questionnaires for sexual function assessment such as Arizona Sexual Experience Scales (ASEX) [25], Brief Sexual Function Inventory [22,23], Clinical Global Impression for Sexual Function (CGI-SF) [27], Erectile Dysfunction Intensity Scale [8,26], Female Sexual Function Index [22,24], International Index of Erectile Function with 15-item [22,23,27], and Sexual Desire Inventory -2 [27]. Any minor and major adverse effects related to the interventions and the number of participants who dropped out and adverse effects were also retrieved;…”

“…Two quasi-experimental studies had set the minimum duration of MMT at 30 days [8,26]. Other eligibility criteria included lack of the following conditions; other psychiatric comorbidities or conditions [10,[22][23][24][25], other substance use disorder [23,24,36], obvious organic illnesses [8,26,27,36], not on other psychotropic drugs [8, 22-24, 27, 36], anti-viral treatment [8,24,27], and sexual enhancement therapy [8,24,27], somatic problems [22], current marital issues [22], non-adherence to the protocol [24], allergy [22], intention to become pregnant, pregnancy, or lactation [24], and adverse effects related to treatment [24].…”

“…Only two RCT studies on bupropion as a treatment of sexual dysfunction were eligible for meta-analysis. The mean and standard deviation of the total ASEX score [36] and CGI-SF [27] were included in the analysis to calculate SMD. A meta-analysis of two RCT studies with a total of 132 patients demonstrated a significant effect of bupropion in the treatment of sexual dysfunction with a SMD of 0.53; 95% confidence interval of 0.19-0.88; P < 0.01; I 2 =0 (Figure 3).…”