This discussion focuses on the historical trends of carbamazepine in the treatment of acute mania, acute bipolar depression, and as maintenance treatment for bipolar disorder. Clinical implications of efficacy, safety, tolerability, and drug interactions associated with carbamazepine are discussed as well.
Important progress in bipolar disorders therapeutics began in the 1970s with lithium and the conventional antipsychotics, and continued in the 1980s with carbamazepine, in the 1990s with divalproex, and in the 2000s with lamotrigine and the introduction of the atypical antipsychotics. Electroconvulsive therapy (ECT) has been used throughout these periods and still has a place in bipolar disorder, especially for severe, treatment-resistant, and very acute cases.
Immediate-release carbamazepine was first approved for epilepsy in 1974, followed by approval of carbamazepine extended release capsules (CBZ ERC) for epilepsy in 1997. Reports of carbamazepine use in bipolar disorder began in 1973 in Japan, when Okuma and colleagues reported antimanic efficacy in manic-depressive psychosis. In 1978, Ballenger and Post reported effective use of carbamazepine in bipolar illness. The initiation of CBZ ERC in bipolar disorder trials began in 2001. In 2004, CBZ ERC received Food and Drug Administration approval for the treatment of acute manic and mixed episodes in patients with bipolar disorder (Slide 4).
In 1988, a survey of American psychiatrists reported moderate-to-marked effectiveness for carbamazepine for the following conditions: partial complex seizures (85%), generalized seizures (82%), trigeminal neuralgia (81%), mania prophylaxis (72%), acute bipolar depression (67%), intermittent explosive disorder (65%), acute mania (62%), and schizoaffective disorder (58%). Historically, carbamazepine has been considered superior to lithium for rapid cycling and mixed mania, bipolar II disorder, bipolar disorder not otherwise specified (NOS), and bipolar disorder with mood incongruent delusions or comorbidity. In multiple controlled trials, carbamazepine was as effective as lithium in the treatment of acute mania. Limitations of early controlled carbamazepine trials include lack of parallel placebo groups, small samples (commonly <60 subjects), confounds of concomitant treatments, and low doses used to avoid/attenuate adverse effects.