Newer Anticonvulsants

Several drugs that have been approved by the FDA as anticonvulsants have been studied as possible mood stabilizers or antimanic drugs (lamotrigine, gabapentin, and topiramate). In spite of extremely limited data on short- or long-term efficacy, their use for the treatment of bipolar disorder and refractory depression in the United States has become widespread.

Lamotrigine is the best studied of the newer anticonvulsants. While showing efficacy for treatment of depression and for maintenance treatment in bipolar patients, it may be less efficacious in the treatment of acute mania (Leadbetter et al., 2002; American Psychiatric Association, 2002). Along with many open-label studies, there is one large multisite placebo-controlled trial of lamotrigine monotherapy for treatment of depression in outpatients with bipolar disorder (Calabrese et al., 1999). In this study, 200 mg/day of lamotrigine demonstrated significant antidepressant effects in over 50 percent of these patients without inducing mania or rash. Lamotrigine inhibits voltage-gated sodium channels and reduces glutamate. It is absorbed within 1 to 3 hr and has a half-life of 25 hr. Rash can occur in up to 8 percent of adults, and serious rash requiring hospitalization can be seen in up to 0.5 percent of patients. Because of the possibility of Stevens-Johnson syndrome, toxic epidermal necrolysis, or angioedema, all rashes should be regarded as potentially serious and monitored closely. Low starting doses (25 mg/day) and slow titration may help reduce the occurrence of rash.

Gabapentin has been studied as both a monotherapy and adjunctive treatment for mania and bipolar depression (Cabras et al., 1999), and while the initial results were generally favorable, subsequent trials failed to show efficacy. Because of this, gabapentin is not recommended for use in mood disorders (American Psychiatric Association, 2002).

Topiramate inhibits rapid firing at voltage-dependent sodium channels, antagonizes kainate binding to the AMPA receptor, and potentiates the effects of GABA at the GABA-A receptor. In a small number of cases, topiramate addition to ongoing treatment with other drugs has been reported to be effective in reducing acute mania or refractory depression (Yatham et al., 2002). It has a half-life of 20 hr and is usually dosed twice daily. Eighty percent of the drug is excreted unchanged in the urine.

In the presence of metabolism-enhancing drugs, it is more extensively metabolized by the liver, causing the plasma levels and half-life to decrease by up to 50 percent. Topiramate can interfere with the efficacy of oral contraceptives, therefore women of child-bearing potential should be counseled and alternative sources of birth control should be considered. The most common side effects of topiramate include somnolence, dizziness, ataxia, speech and cognitive disorders, fatigue, and weight loss. Up to 20 percent of patients experience weight loss, a side effect that has led to the use of topiramate in psychiatric patients solely for this property (Yatham et al., 2002).

Understanding And Treating Bipolar Disorders

Understanding And Treating Bipolar Disorders

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