Mirtazapine Compared With Paroxetine in Major Depression

Background: The aim was to compare the efficacyand tolerability of mirtazapine with those of paroxetine.

Method: 275 outpatients with a diagnosis ofmajor depressive episode (DSM-IV) and a score >= 18 on the17-item Hamilton Rating Scale for Depression (HAM-D-17) wererandomly assigned to 6 weeks of treatment with mirtazapine (15-45mg/day) or paroxetine (20-40 mg/day). Efficacy was assessed bythe HAM-D-17, Hamilton Rating Scale for Anxiety (HAM-A), andClinical Global Impressions scales (Severity and Improvement),and analyses were performed on the intent-to-treat sample (127mirtazapine-treated patients and 123 paroxetine-treatedpatients).

Results: Mean daily doses were 32.7 mg ofmirtazapine and 22.9 mg of paroxetine. Thirty patients in themirtazapine group and 33 in the paroxetine group dropped out.Both drugs were equally effective in reducing symptoms ofdepression. At week 1, the mean HAM-D-17 total score wassignificantly lower in mirtazapine- than paroxetine-treatedpatients (16.5 vs. 18.8, p = .0032). Similarly, significantlymore mirtazapine-treated patients were HAM-D-17 responders (>=50% decrease from baseline) at weeks 1 (23.2% vs. 8.9%, p = .002)and 4 (58.3% vs. 44.5%, p = .04). Both treatments were equallyeffective in reducing anxiety. However, the reduction in meanHAM-A total score was significantly greater with mirtazapine thanwith paroxetine at week 1 (-5.1 vs. -3.5, p = .0435).Tolerability of both treatments was good, with more nausea,vomiting, tremor, and sweating in the paroxetine group and moreweight increase and influenza-like symptoms in the mirtazapinegroup.

Conclusion: Mirtazapine and paroxetinewere equally effective after 6 weeks of therapy and were bothwell tolerated. A potentially faster onset of overall therapeuticefficacy of mirtazapine was suggested by significant differencesbetween treatments after 1 week of therapy that were due toslightly larger improvements of several core symptoms ofdepression as well as distinct prevention of treatment-emergentworsening of anxiety and physical components of depression.