Augmentation with olanzapine in TCA-refractory depression with melancholic features: a consecutive case series

Using an 8-week, open label study design, we report the effect of augmentation strategy with olanzapine in hospitalized depressive patients with melancholic features who had insufficient response to a tricyclic antidepressant (TCA), amitriptyline. Subjects were hospitalized patients meeting the criteria of DSM-IV major depressive disorder with melancholic features who had been suffering from residual symptoms after treatment of amitriptyline. After study entry, olanzapine was added to amitriptyline and the dose was adjusted according to patients' clinical condition. Data were analyzed using an intent-to-treat methodology, with last observation carried forward. Paired t-test was adopted to assess the data from baseline to endpoint. Of 26 patients who enrolled in this study, 23 patients completed the trial and 3 patients dropped out. The mean dose of olanzapine was 6.5 (SD = 2.4) mg/day. The mean score of Montgomery-Asberg Depression Rating Scale (MADRS) was significantly decreased from 33.6 (SD = 3.5) to 20.8 (SD = 9.1) during this study (37.9% from baseline) (p < 0.001). Ten patients (38.5%) were considered as responders (50% or greater reduction in MADRS scores from baseline). These results suggest that augmentation with olanzapine in TCAs-resistant melancholia may be effective and well tolerated. We cannot draw any conclusion with certainty from the open-label, uncontrolled clinical trial. Double blind, controlled trial is needed to confirm this preliminary finding.