PubMed · 16154673
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Steven H Jones, Nick Tarrier. 2005-09-09. New developments in bipolar disorder.. https://doi.org/10.1016/j.cpr.2005.07.001
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Valproate is principally effective in manic aspects of bipolar disorder. Tolerability has been somewhat more favorable for valproate than comparators, with the frequent adverse effects being gastrointestinal disturbances and weight gain. Total cholesterol and low-density lipoproteins are reduced by valproate. Valproate is effective and well tolerated when combined with lithium or antipsychotic drugs. Valproate is efficacious in mixed and euphoric mania. In studies of maintenance versus placebo and active comparators, patients initially treated with divalproex for mania had more robust long-term benefits than in the full sample analyses. In maintenance treatment, patients whose valproate serum levels were between 75 and 99 microg/ml had longer time to discontinuation for any reason or a new mood episode than did patients receiving placebo. The profile of utility in bipolar disorders is principally for core features of manic symptomatology (e.g., impulsivity, hyperactivity and irritability), with little evidence of benefit for anxiety or psychosis. Valproate appears useful in other disorders that have behavioral dimensions inclusive of the domains that valproate benefits in bipolar disorders, such as schizophrenia.
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.
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.