Studies of 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.

Extended-release carbamazepine versus lithium in management of acute mania in male inpatients with bipolar I disorder

“…At this time, several small studies reported the anti-manic effects of carbamazepine as well as its prophylactic effects against the recurrence of manic and depressive episodes in patients with bipolar disorder. Over the last several decades, many double-blind, controlled trials demonstrated the efficacy of carbamazepine in the treatment of acute mania in bipolar disorder, with response rates similar to those of lithium [10]. Early controlled trials of carbamazepine in the treatment of acute mania were conducted with conventional immediate-release formulations and confounded by co-administration with lithium or standard antipsychotics [10].…”

“…Over the last several decades, many double-blind, controlled trials demonstrated the efficacy of carbamazepine in the treatment of acute mania in bipolar disorder, with response rates similar to those of lithium [10]. Early controlled trials of carbamazepine in the treatment of acute mania were conducted with conventional immediate-release formulations and confounded by co-administration with lithium or standard antipsychotics [10]. But, the established correlation between fluctuations in serum levels of carbamazepine and intermittent side effects helped prompt the development of extended-release formulations of carbamazepine for use in epilepsy.…”

“…But, the established correlation between fluctuations in serum levels of carbamazepine and intermittent side effects helped prompt the development of extended-release formulations of carbamazepine for use in epilepsy. The subsequent use of extended-release carbamazepine in patients with epilepsy provided clinical evidence that, compared with immediate-release formulations, extended-release carbamazepine was associated with lower peak serum concentrations, decreased circadian toxicity, and decreased central nervous system side effects [10]. Since extended-release formulations of carbamazepine have been developed to decrease daily fluctuations in the serum concentration level of carbamazepine and improve dosing convenience, several large clinical trials have recently been conducted to assess the efficacy and tolerability of a novel, beaded, extended-release formulation of carbamazepine in bipolar disorder [10][11][12].…”

“…The subsequent use of extended-release carbamazepine in patients with epilepsy provided clinical evidence that, compared with immediate-release formulations, extended-release carbamazepine was associated with lower peak serum concentrations, decreased circadian toxicity, and decreased central nervous system side effects [10]. Since extended-release formulations of carbamazepine have been developed to decrease daily fluctuations in the serum concentration level of carbamazepine and improve dosing convenience, several large clinical trials have recently been conducted to assess the efficacy and tolerability of a novel, beaded, extended-release formulation of carbamazepine in bipolar disorder [10][11][12]. The beneficial effects of extended-release carbamazepine have been reviewed from different aspects by some other scholars as well [13,14].…”

Quantitative Phase Analyses Through The Rietveld Method with X-Ray Powder Diffraction Data of Heat-Treated Carbamazepine Form III

“…2 As an oral preparation, CBZ has a well-established therapeutic profile with nearly 40 years of clinical use in the United States and around the world. 3 Concerning its crystal structures, CBZ crystallizes in four different anhydrous polymorphs. A complete list of references, with the different nomenclature of these four CBZ polymorphs, can be found in the work of Grzesiak et al 4 Moreover, CBZ can form a dihydrate 5,6 and several cocrystals or molecular adducts.…”