Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder

We aimed to compare the antidepressant and anxiolytic effects, tolerability and effects on quality of life of mirtazapine and citalopram in a randomiz ed, double-blind, multicentre, 8-week study. Patients with a Major Depressi ve Episode (DSM-TV) and a baseline score of greater than or equal to 22 on the Montgomery-Asberg Depression Rating Scale (MADRS) were randomized to 8 weeks treatment with either mirtazapine (n = 137, 15-60 mg/day) or citalopr am (n = 133, 20-60 mg/day). Efficacy was evaluated by the MADRS, Hamilton A nxiety Scale (HAM-A), Clinical Global Impression scales (CGI), the Leeds Sl eep Evaluation Questionnaire (LSEQ) and Quality of Life Enjoyment and Satis faction Questionnaire (QLESQ). The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method. Vi tal signs and laboratory variables are measured and adverse events recorded at each weekly visit. The magnitude of reduction from baseline in group me an MADRS scores was large in both groups, reaching after 8 weeks of treatme nt mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram gr oup. Both treatments also resulted in a substantial improvement in anxiety symptoms, sleep disturbances and quality of life, and high percentage of re sponders. However, at day 14, statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS, HAM- A and CGI-Severity of illness and Quality of life scores. A difference of 2 .3 points on MADRS favouring mirtazapine is considered indicative for a cli nically relevant superiority between two proven antidepressants, Mirtazapin e treatment was also related to faster improvement of sleep, quality of sle ep and improved alertness following awakening, as shown by statistically si gnificant differences on the self-rating LSEQ at various time points. There were no differences between two treatment groups on self-rating QLSEQ. Bot h drugs were well tolerated, with a low number of patients in either group prematurely terminating the study due to adverse events (mirtazapine: 3.6%, citalopram, 3.0%). Sweating and nausea were statistically significantly mo re frequent in the citalopram group and increased appetite and complaints o f weight increase in the mirtazapine group. There were no clinically releva nt changes in laboratory parameters and vital sign variables with either tr eatment, except for clinically relevant increase in body weight, occurring more frequently in mirtazapine patients. In this study, mirtazapine and cit alopram were equally effective in reducing symptoms of depression and anxie ty, and well tolerated. However, mirtazapine was significantly more effecti ve than citalopram after 2 weeks of treatment on the MADRS, HAM-A and CGI S everity of illness and Quality of life scales. This finding, consistently p resent at all major efficacy variables, suggests potentially faster onset o f efficacy of mirtazapine over citalopram. Int Clin Psychopharmacol 14:329- 337 (C) 1999 Lippincott Williams & Wilkins.