This research was supported by an investigator-initiated study grant from Ortho-McNeil Neurologics, Inc., which provided financial support and study medication. KNRC has received grant support and has been a consultant to Ortho-McNeil Neurologics. DJK, HP, VJ, RB, JB, PS, PH, JSB, and SG have no reported conflicts of interest. KNRC and SG, as co-editors of this journal, have not had any influence on the acceptance or rejection of the manuscript, which was overseen by other senior Editorial Board members.
A placebo-controlled, random-assignment, parallel-group pilot study of adjunctive topiramate for patients with schizoaffective disorder, bipolar type
Article first published online: 5 SEP 2007
Volume 9, Issue 6, pages 609–617, September 2007
How to Cite
Roy Chengappa, K., Kupfer, D. J., Parepally, H., John, V., Basu, R., Buttenfield, J., Schlicht, P., Houck, P., Brar, J. S. and Gershon, S. (2007), A placebo-controlled, random-assignment, parallel-group pilot study of adjunctive topiramate for patients with schizoaffective disorder, bipolar type. Bipolar Disorders, 9: 609–617. doi: 10.1111/j.1399-5618.2007.00506.x
- Issue published online: 5 SEP 2007
- Article first published online: 5 SEP 2007
- Received 30 September 2005, revised and accepted for publication 30 April 2006
- bipolar type;
- body mass index;
- body weight;
- clinical trial;
- schizoaffective disorder;
Objectives: This pilot study evaluated the efficacy and safety of adjunctive topiramate compared with placebo in the treatment of patients with a diagnosis of schizoaffective disorder, bipolar type (SAD-BT).
Methods: A sample of 48 adult patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnosis of SAD-BT (supported by the Structured Clinical Interview for DSM-IV Axis I Disorder, Patient Edition) were randomly assigned in a 2:1 ratio (favoring topiramate) to 8 weeks of double-blind treatment with topiramate (100–400 mg/day) or placebo. Patients who had achieved a ≥20% decrease from baseline in their Positive and Negative Syndrome Scale (PANSS) total scores were given the opportunity to continue for an additional 8 weeks of double-blind treatment. The dosage of the study medicine was continued unchanged from the earlier 8-week study period. At the end of the study period, the study medicine was tapered and discontinued over a 2-week period. Primary efficacy was assessed at 8 weeks using the mean change between treatment groups of the PANSS total scores in the intent-to-treat population of randomized patients. Several secondary measures were also assessed. Safety analyses included monitoring of adverse events, vital signs, electrocardiogram (ECG) and laboratory values.
Results: Even though both treatments reduced scores on various psychopathology rating scales, adjunctive topiramate treatment (nearly 275 mg/day) did not show increased efficacy relative to placebo on the primary outcome measure (PANSS scale) or any of the secondary outcome measures. Topiramate-treated patients lost significantly more body weight than placebo-treated patients, which led to a significant reduction in body mass index (BMI). Relative to adjunctive placebo, topiramate-treated patients experienced higher rates of paresthesia, sedation, word-finding difficulty, sleepiness, and forgetfulness, but these differences were not statistically significant. There were no clinically significant abnormalities in either the ECG or laboratory results. There were no serious adverse events in the study. Further, there was no worsening of the PANSS total scores (to ≥10% from baseline), and no significant differences between the treatments on worsening of total Montgomery–Asberg Depression Rating Scale (MADRS) scores [1/13 (7.7%) for placebo; 1/25 (4.0%) for topiramate].
Conclusions: This pilot study did not support clinical efficacy for adjunctive topiramate treatment in patients with SAD-BT. There were no major safety or tolerability issues in this study. Confirming the results of other studies, topiramate-treated patients did experience greater body weight loss and reduction in BMI.