Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation.
This double-blind study compared initial combination therapy against monotherapy using two antidepressant drugs with complementary mechanisms of action on the serotonin (5-HT) and norepinephrine (NE) systems. Sixty one adult patients with a DSM-IV diagnosis of unipolar depression were randomized to receive mirtazapine (30 mg/day), paroxetine (20 mg/day), or the combination of both drugs for 6 weeks. Response at week 4 was defined as a 30% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS), and at week 6 as a 50% reduction in the MADRS. Remission was defined as a reduction in the MADRS score to 10 points or less. After 4 weeks, non-responders in the monotherapy groups had their medication dose increased by 50%. After 6 weeks, non-responders on monotherapy had the second trial drug added to their current regimen. Non-responders on combination therapy had the dosage of both drugs increased by 50%. There was a significantly greater decrease in MADRS scores in the combination group compared to the monotherapy groups at days 28, 35 and 42, with a 10 point difference separating the combination from the monotherapies at day 42. Remission rates at week 6 were 19% on mirtazapine, 26% on paroxetine, and 43% on the combination. Fifteen patients in the mirtazapine arm and 10 in the paroxetine arm who did not respond had the other drug added to their current regimen, and 5 on the combination had an increase in dose of both drugs secondary to non-response. Of these 30 patients, approximately 50% went on to achieve remission in the subsequent 2 weeks. These results indicate that the combined use of two antidepressants was well tolerated and produced a greater improvement than monotherapy.
Department of Psychiatry, McGill University, 1033 Avenue des Pins Ouest, Montréal, Québec, Canada H3A 1A1. pierre.blier@rohcg.on.ca
Pierre
P
Blier
Gabriella
G
Gobbi
Julie E
JE
Turcotte
Claude
C
de Montigny
Nathalie
N
Boucher
Chantal
C
Hébert
Guy
G
Debonnel
D000328:Adult; D000704:Analysis of Variance; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003187:Compliance / Q000502:physiology; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004563:Electrochemistry / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D017374:Paroxetine / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D017374:Paroxetine; D000078785:Mirtazapine