Efficacy and safety of combination of risperidone and haloperidol with divalproate in patients with acute mania

Abstract

Objective. The current study evaluated the efficacy and safety of risperidone and haloperidol as an adjunctive agent in combination with divalproate in patients with an episode of acute mania. Methods. This 6-week randomized, single-blind study was conducted in psychiatric wards of a mental hospital. A total of 41 patients were randomly assigned to the risperidone (risperidone plus divalproate) or haloperidol groups (haloperidol plus divalproate). Efficacy was assessed by changes in symptom rating scales [Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) scores]. Safety and tolerability were assessed by monitoring the Extrapyramidal Symptom Rating Scale (ESRS) and Hamilton Rating Scale for depression. Results. Mean doses at baseline, and at weeks 4 and 6 were 3.77, 4.95 and 5.00 mg/day of risperidone and 5.89, 9.95 and 8.58 mg/day of haloperidol, respectively. Risperidone was shown to have significant anti-manic effects which was observed as early as week 1, following start of treatment. The BPRS scores were in favor of risperidone at week 2. Patients receiving risperidone exhibited significant greater global improvement on the CGI, as early as week 2 and over the entire treatment period, than haloperidol after 4 weeks of treatment. The ESRS at endpoint were significantly higher in the haloperidol patients. Conclusions. Risperidone plus divalproate was more efficacious than haloperidol plus divalproate for treatment of acute mania, and was well tolerated due to its evidence showing rapid anti-manic action, effective and sustained control of manic and psychotic symptoms and a favorable safety and tolerability profile in acute mania.

Key Words::

• Mania
• risperidone
• haloperidol
• divalproate
• efficacy

Acknowledgements

This project was partly supported by the funding support of a pharmaceuticals company Taiwan. The authors thank Dr Shih-Ku Lin and Dr Hsin-Cheng Liu in Taipei City Psychiatric Center for their advice. This study also was performed with the assistance of all doctors and staff of Jianan Mental Hospital. The statistical analysis of this study was help and performed by Chia-Min Chen statistician, PhD, in the General Clinical Research Center, Jianan Mental Hospital, and Weir-Sen Lin, DSc, in the Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Taiwan.

Statement of Interest

None.