Dual-dual action? Combining venlafaxine and mirtazapine in the treatment of depression

OBJECTIVE: Venlafaxine and mirtazapine in combination are increasingly used in clinical practice to treat treatment-refractory depression. Putative efficacy for this combination of antidepressants, beyond that of monotherapy, stems from their synergistic actions. This paper describes a prospective case series that examined the efficacy of the venlafaxine-mirtazapine combination in the treatment of depressed patients who had failed at least one antidepressant trial. METHOD: Twenty-two depressed patients with major depression were treated with venlafaxine and mirtazapine in combination for an average of just under 8 weeks. Baseline ratings on the 17-item Hamilton Depression Rating Scale (HAM-D(17)), Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression-Severity Scale (CGI-S) were repeated at end-point, determined by the naturalistic termination of the depressive treatment episode or the discontinuation of the combination treatment due to adverse effects. The length of treatment until end-point was documented for each patient. Descriptive statistics were used on the collated data. RESULTS: At baseline, mean scores were 28.8 (SD=3.8) for HAM-D(17), 30.1 (SD=5.8) for MADRS, and 4.5 (SD=0.5) for CGI-S, reflecting a cohort at the moderate to severe end of the spectrum. At end-point, mean absolute scores were 10.2 (SD=4.7) for HAM-D(17), 10.8 (SD=4.6) for MADRS, and 2.3 (SD=0.6) for CGI-S. Mean change from baseline was 18.6 (SD=6.4) for HAM-D(17), 19.3 (SD=6.8) for MADRS, and 2.3 (SD=0.6) for CGI-S. Mean duration of treatment was approximately 8 weeks, producing a response rate of 81.8% and a remission rate of 27.3%. Only one patient was unable to tolerate the combination although nearly half (10) had significant side-effects during treatment. CONCLUSION: This study demonstrates relatively high response and remission rates that are encouraging and contribute to the efficacy database for this antidepressant combination. Further studies using randomized controlled designs are needed.