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Thirty Years of Clinical Experience with Carbamazepine in the Treatment of Bipolar Illness

Principles and Practice


Carbamazepine began to be studied in a systematic fashion in the 1970s and became more widely used in the treatment of bipolar disorder in the 1980s. Interest in carbamazepine has been renewed by (i) the recent US FDA approval of a long-acting preparation for the treatment of acute mania; (ii) studies suggesting some efficacy in bipolar depression; and (iii) evidence of prophylactic efficacy in some difficult-to-treat subtypes of bipolar illness. A series of double-blind controlled studies of the drug were conducted at the US National Institute of Mental Health from the mid-1970s to the mid-1990s. This review summarises our experience in the context of the current literature on the clinical efficacy, adverse effects and pharmacokinetic interactions of carbamazepine.

Carbamazepine has an important and still evolving place in the treatment of acute mania and long-term prophylaxis. It may be useful in individuals with symptoms that are not responsive to other treatments and in some subtypes of bipolar disorder that are not typically responsive to a more traditional agent such as lithium. These subtypes might include those patients with bipolar II disorder, dysphoric mania, substance abuse co-morbidity, mood incongruent delusions, and a negative family history of bipolar illness in first-degree relatives. In addition, carbamazepine may be useful in patients who do not adequately tolerate other interventions as a result of adverse effects, such as weight gain, tremor, diabetes insipidus or polycystic ovarian syndrome.

We review our clinical and research experience with carbamazepine alone and in combination with lithium, valproic acid and other agents in complex combination treatment of bipolar illness. More precise clinical and biological predictors and correlates of individual clinical responsiveness to carbamazepine and other mood stabilisers are eagerly awaited.

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    The use of trade names is for product identification purposes only and does not imply endorsement.


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This research was supported (in part) by the Intramural Research Program of the NIH, National Institutes of Mental Health.

Thomas Uhde has no conflicts of interest that are directly relevant to the content of this review. Robert Post and James Ballenger have received honoraria and consultancies from several pharmaceutical companies including Shire, GlaxoSmithKline, Bristol Myers Squibb, AstraZeneca and Abbott. Terence Ketter has received honoraria, consultancies and grants from a number of pharmaceutical companies including Shire.

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Correspondence to Prof. Terence A. Ketter.

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Post, R.M., Ketter, T.A., Uhde, T. et al. Thirty Years of Clinical Experience with Carbamazepine in the Treatment of Bipolar Illness. CNS Drugs 21, 47–71 (2007).

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  • Bipolar Disorder
  • Carbamazepine
  • Valproic Acid
  • Lamotrigine
  • Oxcarbazepine