Olanzapine in the treatment of apathy in previously depressed participants maintained with selective serotonin reuptake inhibitors: An open-label, flexible-dose study

Background: We report a clinical trial of olanzapine in the treatment of prominent apathy in the absence of depression in patients on long-term treatment with selective serotonin reuptake inhibitors (SSRIs) for nonpsychotic major depression. Method: Participants were 21 men and women who met DSM-IV criteria for major depressive disorder in full remission (Montgomery-Asberg Depression Rating Scale [MADRS] score less than or equal to 12) who had been taking an SSRI for at least 3 months. Data are presented (last observation carried forward) based on 20 enrolled participants who completed at least I follow-up visit. Participants had significant symptoms of apathy, defined as a Clinical Global Impressions-Severity of Illness scale (CGI-S) score greater than or equal to 3, an Apathy Evaluation Scale (AES) score > 30, and a MADRS item 8 (inability to feel) score greater than or equal to 2. Participants with a personal or family history of psychosis were excluded. Olanzapine was titrated in 2.5-mg increments at weekly intervals, until CGI-S score improved greater than or equal to 2 points from baseline or greater than or equal to 1 point with dose-limiting side effects. and participants continued in the protocol for 8 weeks at a stable dose following this improvement. Results: Improvement was clinically evident and demonstrable on all symptom assessments: AES (mean +/- SD change in score = -21.3 +/- 8.7 p <.0001), CGI-S (-2.7+/-0.9: p <.0001). MADRS (-5.6+/-5.9 p =.001), and MADRS item 8 (-2.2+/-1.4 p <.0001). The mean dose of olanzapine was 5.4+/-2.8 mg/day. Conclusion: These preliminary data Suggest that olanzapine may be effective in treating apathy syndrome in nonpsychotic patients taking SSRIs.