A DOUBLE-BLIND COMPARISON OF MOCLOBEMIDE AND THIORIDAZINE VERSUS MOCLOBEMIDE AND PLACEBO IN THE TREATMENT OF REFRACTORY, SEVERE DEPRESSION

In a multicenter study of 78 severely depressed inpatients (44 women a nd 34 men; age range, 23 to 70 years), the efficacy, onset of efficacy , and tolerability of the reversible monoamine oxidase-A inhibitor moc lobemide (450 mg/day) in combination with thioridazine (100 mg/day) we re compared with those of moclobemide (450 mg/day) plus placebo. Patie nts enrolled met the DSM-III-R criteria for severe depression and had a severity score of at least 20 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Additionally, these patients had not responded to at least two standard antidepressants during the 2 ye ars preceding screening and the mean duration of the current episode w as 6 months. After a wash-out period of 3 to 5 days, patients were ran domized to one of the two treatment groups, which at the outset had si milar characteristics. Efficacy was assessed by the HAM-D, a depressio n observation rating for nurses, and a Clinical Global Impression (CGI ) scale. Tolerability assessments included an overall rating, a descri ption of adverse events, vital signs, electrocardiogram, and laborator y tests. After 4 weeks of therapy, both groups of patients showed sign ificant improvements in HAM-D and CGI scores. The response rates (base d on HAM-D greater than or equal to 50% decrease) were 74% for moclobe mide/thioridazine and 77% for moclobemide/placebo, and according to CG I scores, 76 and 72% were ''very much improved'' or ''much improved,'' respectively. Onset of effect was noted after 9.2 and 9.8 days, respe ctively. Overall tolerability at the end of the study was rated ''very good'' or ''good'' in 89% of the moclobemide/thioridazine group and i n 88% of the moclobemide/placebo group. This study demonstrates that m oclobemide is effective and well tolerated in the treatment of resista nt, severely depressed patients. The addition of thioridazine to moclo bemide did not increase efficacy or speed of onset, nor did it signifi cantly impair tolerability.