BACKGROUND The safety and efficacy of the combination of risperidone and topiramate in the long-term treatment of mania were assessed in a 12-month, multicenter open study. METHODS Subjects (N = 58) who met DSM-IV criteria for bipolar disorder and for a manic episode received both risperidone and topiramate for the treatment of their manic symptoms. Patients with mixed episodes were excluded. Risperidone could be discontinued at any point, but patients had to be on topiramate therapy for at least 12 months to be considered completers. Efficacy was assessed with the Young Mania Rating Scale (YMRS) and a modified version of the Clinical Global Impressions for Bipolar Disorder (CGI-BP-M). Safety was assessed with systematic collection of side effect data, weight, and the Hamilton Rating Scale for Depression (HAM-D) scores, to address the risk of switch into depression. RESULTS 41 patients (70.7%) completed the study. There was a significant improvement on the YMRS (p <.001) and the CGI-BP-M subscales for manic symptoms (p <.005) and long-term outcome (p <.005) from week 2 onward. Relapse rates were significantly lower during the 12-month study period compared to the precedent year (p <.0001). There was no increase in depressive symptoms as measured by the HAM-D. 37 patients (63.8 %) experienced at least 1 adverse event, the most frequent of which was somnolence (N = 7, 12.1%). At endpoint, the patients' mean weight had decreased an average of 1.1 +/- 0.4 kg. CONCLUSIONS Despite the limitations inherent to the open design, this naturalistic study suggests that the combination of risperidone and topiramate may be a valuable option for the short- and long-term treatment of mania.