This paper is highly cited because it offers an overview of positive results from the first randomized, double-blind, placebo-controlled trial ever done with extended-release carbamazepine capsules as monotherapy in the treatment of bipolar disorder. Previous controlled evaluations of carbamazepine have been small or confounded by concomitant therapy with lithium or antipsychotics, and all have used immediate-release carbamazepine formulations.

Though carbamazepine has been around for nearly forty years, our study is the first to describe the efficacy and safety of carbamazepine extended-release capsules (an advanced formation of carbamazepine that utilizes a 3-bead delivery system designed to prolong the release of the drug) in bipolar disorder. Extended-release formulations of carbamazepine have been developed in recent years to decrease daily fluctuations in serum carbamazepine concentration and improve dosing convenience. The study data were an essential part of the clinical evidence that subsequently led to FDA approval of carbamazepine extended-release capsules for the treatment of bipolar disorder. It was also interesting in that this trial used a rapid titration schedule championed by Dr. Amir Kalali of Quintiles CNS Therapeutics in San Diego, CA.

Twice-daily carbamazepine extended-release capsules provide a much needed treatment option for patients with bipolar disorder, including patients unable to benefit from other medications. Compared with immediate-release carbamazepine formulations, extended-release formulations have been associated with decreased toxicity, and decreased central nervous system side effects, which can lead to things such as double vision, confusion, and sleepiness. Adverse events during the trial were generally mild to moderate, with most events emerging in the first 2 weeks of treatment. Recently, weight gain and diabetes have become concerns in the management of patients with bipolar disorder. Carbamazepine does not cause significant weight gain or significant blood sugar changes, which should reflect favorably on the risk-benefit ratio of this agent.

This paper was the result of a combined effort of many individuals who were interested in finding a treatment option that worked effectively in both manic states and in the large number of mixed patients, who were both depressed and manic at the same time. There is great satisfaction in knowing that our research efforts have provided important information regarding the real-world use of carbamazepine in a large cohort of patients with bipolar disorder, hopefully leading to improved patient care.