Olanzapine–valproate combination versus olanzapine or valproate monotherapy in the treatment of bipolar I mania: a randomized controlled study in a Chinese population group

BACKGROUND Bipolar disorder (BP) is a mental illness that has a high social burden estimated by disability-adjusted life years. In the present study, we investigated the efficacy of olanzapine-valproate combination therapy versus olanzapine or valproate monotherapy in the treatment of bipolar I mania in a Chinese population group. SUBJECTS AND METHODS Patients aged 19-58 years who had had an acute manic episode of BP were enrolled in the present study and randomly assigned to receive 600 mg sodium valproate daily (group A), 10 mg olanzapine daily (group B), or a combination of 600 mg olanzapine and 10 mg sodium valproate daily (group C) for 4 weeks. The primary outcome was reduction in Young Mania Rating Scale (YMRS) scores. The secondary outcome was assessed with the Clinical Global Impression - Bipolar (CGI-BP) scale. Adverse reactions, such as weight gain, sleepy, and dizziness were also evaluated. Statistical analysis was carried out on a per-protocol basis. RESULTS Patients in groups B and C showed significant improvement in YMRS scores compared with those in group A (P<0.01) during weeks 1-4 of treatment. Patients in group C showed significant improvement in YMRS scores compared with those in group B (P<0.01) only after 4 weeks of treatment. Furthermore, after 3-4 weeks of treatment, patients in groups B and C showed significantly greater improvement in CGI-BP scale scores compared with group A (P<0.05), while Group C demonstrated significantly greater improvement in CGI-BP scale scores than group B (P<0.01). No significant difference existed in extrapyramidal reactions among these groups. Adverse reactions, including weight gain, drowsiness, dizziness, and constipation, were stronger in groups B and C than in group A (P<0.05). CONCLUSION The combination therapy with olanzapine and sodium valproate had higher efficacy than monotherapy in patients with bipolar mania, which provides a crucial insight of the treatment regimen during clinical practice.