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

J Clin Psychiatry. 2002 Mar;63(3):181-6. doi: 10.4088/jcp.v63n0302.

Abstract

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 (chi2= 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 O-desmethylvenlafaxine (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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / pharmacokinetics
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Bupropion / pharmacology*
  • Bupropion / therapeutic use
  • Cyclohexanols / adverse effects
  • Cyclohexanols / blood
  • Cyclohexanols / pharmacokinetics*
  • Cyclohexanols / therapeutic use
  • Cytochrome P-450 CYP2D6 / metabolism
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dopamine Uptake Inhibitors / therapeutic use
  • Drug Interactions
  • Female
  • Fluoxetine / adverse effects
  • Fluoxetine / blood
  • Fluoxetine / pharmacokinetics*
  • Fluoxetine / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / adverse effects
  • Paroxetine / blood
  • Paroxetine / pharmacokinetics*
  • Paroxetine / therapeutic use
  • Serotonin Uptake Inhibitors / blood
  • Serotonin Uptake Inhibitors / pharmacokinetics*
  • Serotonin Uptake Inhibitors / therapeutic use
  • Sexual Behavior / drug effects*
  • Surveys and Questionnaires
  • Treatment Outcome
  • Venlafaxine Hydrochloride

Substances

  • Antidepressive Agents, Second-Generation
  • Cyclohexanols
  • Dopamine Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Bupropion
  • Paroxetine
  • Venlafaxine Hydrochloride
  • Cytochrome P-450 CYP2D6