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 and 34 men; age range, 23 to 70 years), the efficacy, onset of efficacy, and tolerability of the reversible monoamine oxidase-A inhibitor moclobemide (450 mg/day) in combination with thioridazine (100 mg/day) were compared with those of moclobemide (450 mg/day) plus placebo. Patients 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 years preceding screening and the mean duration of the current episode was 6 months. After a washout period of 3 to 5 days, patients were randomized to one of the two treatment groups, which at the outset had similar characteristics. Efficacy was assessed by the HAM-D, a depression observation rating for nurses, and a Clinical Global Impression (CGI) scale. Tolerability assessments included an overall rating, a description of adverse events, vital signs, electrocardiogram, and laboratory tests. After 4 weeks of therapy, both groups of patients showed significant improvements in HAM-D and CGI scores. The response rates (based on HAM-D >or=to50% decrease) were 74% for moclobemide/thioridazine and 77% for moclobemide/placebo, and according to CGI scores, 76 and 72% were "very much improved" or "much improved," respectively. Onset of effect was noted after 9.2 and 9.8 days, respectively. Overall tolerability at the end of the study was rated "very good" or "good" in 89% of the moclobemide/thioridazine group and in 88% of the moclobemide/placebo group. This study demonstrates that moclobemide is effective and well tolerated in the treatment of resistant, severely depressed patients. The addition of thioridazine to moclobemide did not increase efficacy or speed of onset, nor did it significantly impair tolerability. (J Clin Psychopharmacol 1995;15[Suppl 2]:41S-45S)