Dose Decrease and Other Correlates of Relapse in Patients with Schizophrenia or Schizoaffective Disorder During Olanzapine Drug Therapy

Purpose

To assess dose decrease and other variables as correlates of relapse during olanzapine treatment.

Methods

In two 28-week, randomized, double-blind clinical trials, a Cox proportional hazards model was used for post hoc analysis of potential correlates of relapse (defined as ≥20% worsening on PANSS total and CGI-Severity ≥ 3) among patients (N = 271) who responded to 8 weeks of olanzapine treatment (10-20 mg/day). Variables examined included demographics, illness characteristics, baseline symptoms, symptom changes, dose, adverse events, and functioning.

Results

Patients with a lower last dose relative to that of the preceding visit interval were 4 times more likely to relapse during that visit interval than patients without a lower dose (p < 0.001). A similar finding was observed for a decrease in interval modal dose and risk for relapse, although this relationship was more predictive of relapse in the next visit interval (p = 0.027). A dose decrease in women was not associated with relapse (p = 0.922), whereas a dose decrease in men did predict relapse (p < 0.001). Relapse also correlated with the emergence or worsening of a psychiatric adverse event during the same visit interval as relapse (p < 0.001), and during the preceding visit interval (p = 0.007). The occurrence of a nonpsychiatric adverse event was not associated with relapse.

Conclusion

Dose decrease was a significant predictor of relapse in male patients. Psychiatric adverse events were also a significant predictor of relapse. Symptom worsening and dose decrease are both clinical measures that call for closer monitoring of patients due to increased likelihood of relapse.