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 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 1 follow-up visit. Participants had significant symptoms of apathy, defined as a Clinical Global Impressions-Severity of Illness scale (CGI-S) score 3, an Apathy Evaluation Scale (AES) score >30, and a MADRS item 8 (inability to feel) score 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 2 points from baseline or 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.