Historical Review of Carbamazepine for the Treatment of Bipolar Disorder

Abstract

The management of bipolar disorder has seen significant evolution in terms of the number of treatment options now approved for both the acutely manic phase and the maintenance stages of the illness. In addition, new formulations of traditional agents are available for clinicians to use in their treatment approach. One such example is carbamazepine, which has approval by the United States Food and Drug Administration for the treatment of acute and mixed mania in an extended-release formulation that uses a three-bead delivery system. Although the parent compound has been available for decades, its approval for bipolar disorder is recent despite numerous clinical trials that have supported its use in both the acute and maintenance phases of bipolar disorder. Advantages of the new formulation include less fluctuation in plasma concentration and, in general, improved tolerability. However, issues remain with regard to cytochrome P450 drug-related interactions and the need for therapeutic drug monitoring (e.g., drug concentrations, epoxide metabolite concentrations, hematology, and liver function tests) as part of the treatment and monitoring process. We review the current body of literature describing the use of carbamazepine in bipolar disorder during both the acute and maintenance phases of the disorder, including trials of both monotherapy and combination therapy, as well as findings from trials that included patients with rapid cycling and mixed episodes.

Is Anticonvulsant Treatment of Mania a Class Effect? Data from Randomized Clinical Trials

“…However, in the Multicentre study of long‐term treatment of affective and schizoaffective psychoses (MAP) studies, carbamazepine was inferior to lithium for the treatment of classic mania. Carbamazepine provides hepatic enzymes (CYP 3A4) induction that lowers drug levels and may require additional upward dose titration, after some weeks of treatment [49]. Although carbamazepine appears to be less tolerable than valproate for short‐term treatment because of the high incidence of side effects (e.g., gastrointestinal effects, sedation, ataxia, and asthenia), it may offer some advantages in terms of weight gain, polycystic ovarian syndrome, bone loss, and teratogenicity [65].…”

“…Carbamazepine induces medication metabolism, including its own, through cytochrome P‐450 oxidation and conjugation [49]. This enzymatic induction may decrease levels of concomitantly administered medications such as valproate, lamotrigine, oral contraceptives, protease inhibitors, benzodiazepines, and many antipsychotic and antidepressant medications.…”

Mood-Stabilizing Agents

“…Different formulations of carbamazepine appear to be similar in ef fi cacy [ 105 ] . The anticonvulsant was introduced in Japan to treat mania in the early 1970s [ 256,257,317 ] . However, evidence pertaining to possible prophylactic, mood-stabilizing effects of carbamazepine remains limited, despite decades of international use of the drug for long term as well as antimanic treatment for bipolar disorder patients, and it is not FDA approved for long-term mood stabilization.…”

Antiepileptic drugs for the treatment of post-traumatic stress disorder

“…When prescribing CBZ, clinicians should take into account possible drug interactions; side effects, especially blood dyscrasias and hepatotoxicity [29]; and the need for therapeutic drug monitoring [99]. Double-blind, placebocontrolled trials are needed to fully determine the efficacy of CBZ in PTSD.…”