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Lamotrigine: A Review of Clinical Studies in Bipolar Disorders S Zerjav-Lacombe, BSc,(Pharm), PharmD1, E Tabarsi, BA(Psych), BSc(Pharm), PharmD2 |
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Objective: This article reviews published studies on the use of lamotrigine in the
treatment of bipolar disorder (BD). Method: We performed a Medline search to identify the literature data base available on double-blind, open-label studies and case series on the use of lamotrigine to treat BD. Results: Three double-blind studies, 3 open-label studies, and 2 case series have been conducted to date (n = 401 patients). Most patients were either nonresponders or partial responders to other mood stabilizers. Overall, 50% to 83% of the patients responded to lamotrigine; doses in the studies ranged from 50 to 400 mg daily. Switching to mania while on 200 mg of lamotrigine or more was extremely rare, and there were no reports of serious adverse effects during the study periods. Conclusions: Lamotrigine is proving to be an effective agent in the treatment of BD and may be useful for patients who have not responded to other mood stabilizers. (Can J Psychiatry 2001;46:328-333) Key Words: Lamotrigine, bipolar disorder, nonresponders |
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Reports of lamotrigine’s effectiveness in treating bipolar disorder (BD) appeared as early as 1994 (1). Since that time, there have been reports of over 200 cases describing the moderate-to-marked efficacy of lamotrigine in treating BD in the depressed phase, hypomanic, and mixed states (2–9). Several successful cases of the treatment of rapid cyclers have also been described. Although there are several other treatment options, notably lithium, valproate, carbamazepine, verapamil, gabapentin, and more recently, topiramate, there are still patients who do not respond to or tolerate the adverse effects of these agents. Lithium is known to be less effective than valproate and carbamazepine in treating rapid cyclers and has numerous unpleasant adverse effects (10). Valproate and carbamazepine have been found to be less effective than lithium in treating the depressed phase of BD, and adding antidepressants to the treatment regimen of patients with BD runs the risk of switching patients into mania (11–13). This article reviews the clinical studies of lamotrigine treatment of bipolar and unipolar illness. In particular, it addresses its effectiveness in rapid cyclers, in the manic, mixed, and depressed phase of bipolar illness, and its efficacy for treatment-resistant patients. Manuscript
received April 2000, revised, and accepted March 2001. |
Methodology We completed a literature search using lamotrigine as a key word. We then exploded the results to the following subject headings: BD, depressive disorder, depression, affective disorder, psychotic and mood disorder. The exploded disorders and lamotrigine were combined and were limited to continuous update. Lamotrigine Mechanisms of Action There are several hypotheses regarding the mechanism of action of lamotrigine in BD; however, the exact mechanism is still unknown. One theory suggests that lamotrigine inhibits the release of the excitatory neurotransmitters glutamate and aspartate, thus producing antikindling effects and thereby resolving the cycling in BD (14). Another theory proposes that lamotrigine may potentiate effects of dopamine and inhibit the effects of 5-HT3 receptors, resulting in an antidepressant effect (15). Lamotrigine downregulates b-adrenergic receptors, a property that has been found to be associated with antidepressant action (14). Adverse Effects and Drug Interactions The most frequent adverse effects include headache, ataxia, visual disturbances, drowsiness, dizziness, somnolence, |
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