Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjects

Paroxetine inhibits cytochrome P-450 2D6, which is involved in the metaboli sm of mirtazapine. The possible drug-drug interaction between two pharmacol ogically distinct antidepressants, mirtazapine and paroxetine, has been inv estigated in a randomized, three-way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30 mg mirtazapine, 40 mg paroxetine or the combinatio n for 6 days. Assessments included serial blood sampling for pharmacokineti cs at steady state cognitive testing using the test battery of CDR Ltd, a v isual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evalu ation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24 h AUC's of mirtaz apine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazap ine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluat ion Questionnaire, compared with the administration of either drug alone. T he incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest t hat the combination of mirtazapine and paroxetine is unlikely to lead to cl inically relevant drug-drug interactions and can be used without dose adjus tment of either drug. The combination may even be better tolerated than eit her drug alone. Copyright (C) 2001 John Wiley & Sons, Ltd.