CONTROLLED COMPARISON OF NEFAZODONE AND AMITRIPTYLINE IN MAJOR DEPRESSIVE INPATIENTS

Nefazodone, a phenylpiperazine antidepressant, exhibits novel dual act ivity on serotonin (5-HT) neurons; it binds to 5-HT, receptors and inh ibits 5-HT reuptake. Flexible doses of nefazodone (100-400 mg/day) and amitriptyline (50-200 mg/day) were compared in 106 major depressive i npatients in a 6-week double-blind study. Results showed significant s uperiority of amitriptyline over nefazodone on all rating instruments: Montgomery and Asberg depression rating scale (P < 0.0001), Hamilton depression scale (P < 0.0006), Clinical Global Impressions (P<0.0001) and Patient Global Assessment (P < 0.01). A total of 65% of patients u nder amitriptyline and 56% of patients under nefazodone reported adver se events during the study, with significantly more dry mouth in the a mitriptyline group (39% Versus 11%, P = 0.001). Modal daily doses with in the last treatment week reached 242 mg with nefazodone and 124 mg w ith amitriptyline. The lower efficacy of nefazodone, which contradicts comparative trials with imipramine in US patients, is discussed with regard to the dose of nefazodone, probably below the optimal therapeut ic range for melancholic patients, and to the clinical differences bet ween the patient samples.