Olanzapine treatment for tardive dyskinesia in schizophrenia patients: a prospective clinical trial with patients randomized to blinded dose reduction periods

BACKGROUND: Tardive dyskinesia (TD) is a potentially persistent and disabling abnormal involuntary movement disorder. The aim of this 8-month study was to determine if olanzapine treatment could lead to a significant and persistent reduction in preexisting TD. METHODS: Eligible schizophrenia patients met restricted Research Diagnosis criteria of TD requiring, in part, a rating of at least moderate severity (score > or = 3) in one or more of seven body regions on the Abnormal Involuntary Movement Scale (AIMS). Patients received olanzapine, 5-20 mg/day, for 8 months. During this period, they underwent one to two dose reduction periods under blinded conditions. Concurrent changes in TD, psychopathology, parkinsonism and akathisia were assessed with the AIMS, the Positive and Negative Syndrome Scale (PANSS), and the Simpson-Angus and Barnes Akathisia Scales, respectively. RESULTS: A significant reduction in mean AIMS total score was demonstrated at endpoint (n = 92; p < 0.001) as well as at each visit (p < 0.001) and as early as Week 1 on olanzapine. Approximately 70% of patients no longer met the restricted Research Diagnostic criteria for persistent TD (RD-TD) after 8 months of treatment. No statistically significant rebound worsening of TD was found during either blinded drug reduction period. Significant improvement in psychopathology (p = 0.001) and parkinsonism (p < 0.001) was observed. CONCLUSIONS: Improvement in the severity of preexisting TD was achieved with olanzapine and persisted throughout the 8-month study and during each dose reduction period. Overall improvement in clinical status suggests that olanzapine may be effective for the long-term management of schizophrenia patients with preexisting TD.