Carbamazepine extended-release capsules in bipolar disorder

Abstract

Carbamazepine (CBZ) has long been a therapeutic option for bipolar disorder. Carbamazepine extended-release capsules (CBZ-ERC) are a recent formulation of CBZ approved by the US Food and Drug Administration in 2004 for the treatment of acute manic and mixed episodes associated with bipolar I disorder. This new formulation was developed to improve dosing convenience and decrease daily fluctuations in serum CBZ concentration, thereby lowering the incidence of adverse events. Two randomized, double-blind, placebo-controlled trials and an open-label extension study have demonstrated that CBZ-ERC monotherapy is efficacious in patients with bipolar I disorder experiencing either manic or mixed episodes. In these trials, CBZ-ERC was shown to be a safe and well-tolerated therapy. Retrospective chart reviews conducted in private practice settings have shown that clinical response to CBZ-ERC is independent of bipolar subtype, as patients with bipolar I depression and bipolar II disorder responded similarly to patients with bipolar I disorder either manic or mixed episodes. CBZ is currently considered a treatment alternative to lithium and valproate according to the American Psychiatric Association's treatment guidelines for patients with bipolar disorder. Although further study is required, the clinical evidence presented in these studies may change the treatment paradigm.

Keywords: bipolar disorder; carbamazepine; extended-release; mania.

Figure 1

Mean change in YMRS total scores in pooled analysis of 3-week studies of CBZ-ERC in acute mania. *p < 0.0001 compared with placebo following analysis of covariance with baseline score as covariate. Abbreviations: YMRS, Young Mania Rating Scale; LOCF, last observation carried forward; CBZ-ERC, carbamazepine extended-release capsules.

Figure 2

Mean change in YMRS total scores with long-term CBZ-ERC treatment in bipolar disorder patients with manic or mixed episodes. *p < 0.01; ^†p < 0.001; ^‡p < 0.0001 vs baseline (one-sample t-test of mean change from day 1). ^aPatients who were previously placebo in the acute 3-week trials before entrance into the 6-month study. Abbreviations: YMRS, Young Mania Rating Scale; LOCF, last observation carried forward; CBZ-ERC, carbamazepine extended-release capsules.

Figure 3

HDRS total scores from the 6-month CBZ-ERC study including baseline score in the pooled analysis of the 3-week studies. *p < 0.0001, ^†p = 0.0004, ^‡p = 0.0002 based on one sample t-test of mean change from baseline scores of pooled analysis from the 3-week studies. Notes: When scores were based on one sample t-test of mean change from baseline values at day 1 in 6-month study, no statistical significance was detected. Abbreviations: HDRS, Hamilton Depression Rating Scale; LOCF, last observation carried forward; CBZ-ERC, carbamazepine extended-release capsules.