Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: A preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects

Background: This study was designed to evaluate the effect of combining bupropion sustained release (SR) with venlafaxine, paroxetine, or fluoxetine in patients who reported unacceptable sexual dysfunction when treated with monotherapy with the latter 3 agents. Method: Following a minimum of 6 weeks of antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI) or venlafaxine (a serotonin-norepinephrine reuptake inhibitor), eligible subjects received a further 8 weeks of monitored combination therapy with bupropion SR at a dose of 150 mg/day with no alterations to index antidepressant dosing. Results: There was a clinically significant benefit in 14 (78%) of 18 partial responders or nonresponders, and 33% (N = 6) achieved a full response (X-2 = 8.06, df = 2, p = .017). Sexual dysfunction, particularly a decrease in orgasmic delay, was also significantly improved with combination therapy (men: paired t = -2.1, df = 6, p = .08 women: paired t = -3.0, df = 7, p = .02). Plasma monitoring of drugs and their metabolites revealed a statistically significant increase in venlafaxine levels (F = 6,89, df = 4,24; p = .001) accompanied by a decrease in 0-desmethyl-venlafaxine (F = 14,26; df = 4,24; p < .0005) during combined treatment with bupropion SR. There were no statistically significant changes in plasma levels of SSRIs (paroxetine and fluoxetine) during the trial. Conclusion: Bupropion had an effect on the pharmacokinetics of venlafaxine but not those of the SSRIs. Further investigation of combination treatments under randomized, double-blind conditions is recommended.