To the Editor: Levetiracetam is a novel antiepileptic drug with antikindling properties but no known mechanism that directly affects inhibitory neurotransmitters or excitatory amino acids. Although a number of newer anticonvulsants have begun to receive attention for their possible antimanic and/or antidepressant efficacy, we know of no published reports regarding these potential properties of levetiracetam. We report a patient with acute mania that stabilized with open-label levetiracetam monotherapy, recurred after drug cessation, and restabilized after drug reintroduction.

Although the patient’s drug discontinuation was unplanned, the swift resolution of reemergent mania after abrupt cessation was striking. The high degree of tolerability and favorable side effect profile of levetiracetam suggests it may be useful, in light of the high rates of noncompliance with many existing pharmacotherapies for bipolar disorder. Current neuropsychopharmacologic theories emphasize the importance of the upregulation of γ-aminobutyric acid (GABA) and the lowering of excitatory amino acids to explain the occurrence of mood stabilization with anticonvulsants. Newer anticonvulsants often become regarded as good candidates for mood stabilizers on the basis of these mechanisms. However, negative studies of the use of gabapentin +(3) and tiagabine +(4) to treat mania call into question such generalizations and suggest that additional mechanisms may be involved. The unique neuropharmacology of levetiracetam, combined with the present observations, warrant controlled studies to investigate further its possible thymoleptic properties. Pending further reports, these findings regarding one patient must be interpreted with caution.