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 < or = 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 > or = 3, an Apathy Evaluation Scale (AES) score > 30, and a MADRS item 8 (inability to feel) score > or = 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 > or = 2 points from baseline or > 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.