Objective: To evaluate the efficacy, safety, and tolerability of eslicarbazepine acetate (ESL), a once-daily voltage-gated sodium channel blocker, in patients with acute mania.

Methods: Subjects met DSM-IV criteria for acute manic or mixed episode with a Young Mania Rating Scale (YMRS) score ≥20 and onset within 2 weeks of randomization. 162 subjects were randomized to initial QD doses of 600 mg (n=64) or 800 mg (n=58) or placebo (n=40); subjects were then titrated every three days to a maximum dose of either 1800 mg QD (600 mg steps) or 2400 mg QD (800 mg steps)

Results: YMRS total scores decreased (±SD) -10.0±9.73, -12.2±7.85, and -14.1±8.92 in the placebo, ESL 600-1800 mg, and ESL 800-2400 mg groups, respectively. The difference of 3.9 between the 800-2400 mg group and placebo was not significant (p=0.0523). There were no significant differences in the responder rates. 50.9% of subjects were in full remission (YMRS<12) at week 3 in the ESL 800-2400 mg QD group, versus 27.5% in the placebo group (p=0.0232). There were no clinically meaningful differences in TEAE’s, laboratory or safety parameters.

Conclusions: The study failed to demonstrate a significant difference in the YMRS change from baseline and responders. A significantly higher percentage of patients in the ESL 800-2400 mg group were in full remission at week 3. Limitations of the study include: small number of subjects, baseline imbalances between the treatment groups, and a higher % of subjects with initiation of benzodiazepines or antiepileptics after randomization. These results warrant further investigation.