Anticonvulsants, including valproate and carbamazepine, have established efficacy in the treatment of mania. The anticonvulsant, lamotrigine, has been reported to have antimanic and antidepressant efficacy, and mood-stabilising effects in case reports and preliminary open trials. The efficacy and tolerability of lamotrigine has been compared with olanzapine and lithium in a randomised, prospective, controlled fashion over a period of 4 weeks’ treatment in a total of 45 hospitalised patients with DSM-IV-defined mania. Significant improvements of a similar magnitude were observed for all treatment groups and lamotrigine was well tolerated. Mechanisms of action proposed to explain the antimanic activity of lamotrigine include inhibition of voltage-sensitive and use-dependent sodium channels, inhibition of glutamate release and calcium channel blockade. Platelet studies have indicated supersensitivity of glutamate receptors and increased intracellular calcium concentrations in patients with mania. Further clinical and mechanistic studies of lamotrigine use in mania are warranted.
Treatment of mania poses a number of specific management problems. During manic episodes, patients have inflated self-esteem, excess energy, increased goal-directed activity and they may be highly irritable. Their behaviour during such an episode may lead to physical harm, and difficult social and occupational situations (Bauer, 1993). However, the symptoms of mania are often not unwelcome to many patients and, as a consequence, they are reluctant to receive treatment that may reduce these feelings. This reluctance is exacerbated by the fact that the side effects of some antimanic drugs, for example lithium and valproate, are problematic and include sedation, acne and weight gain (Bauer, 1993). Improved therapies for the treatment of mania which have fewer side effects are therefore important to improve compliance and outcome, particularly in patients with type I bipolar disorder.
For many years the standard treatment for mania has been lithium, but there are limitations to its safety and efficacy (Maj et al., 1998). Lithium use is associated with tremor, blurred vision, lack of co-ordination, and may occasionally cause serious and irreversible neurotoxicity, even at therapeutic concentrations (Cookson, 1997). Other mood stabilisers, such as valproate and carbamazepine, neuroleptics and antidepressants have become the principal alternatives (Bowden, 1998), although valproate use is associated with nausea, weight gain, and, in females, alopecia, hyperinsulinaemia, polycystic ovaries and hyperandrogenism (Isojärvi et al., 1993). Combination therapy has been common in the treatment of bipolar disorder to optimise symptom control, but poses the risk of adverse drug reactions. Preliminary data suggest that the anticonvulsant lamotrigine has antimanic and antidepressant efficacy (Walden et al., 1998). This review will concentrate on the evidence and theories presently available to support and explain the efficacy of lamotrigine in the treatment of mania in patients with bipolar disorder.
