The initial premise in evaluating lamotrigine as an anticonvulsant was that it might possess sufficient dihydrofolate reductase inhibition to decrease folate activity, a mechanism known to reduce epileptic effects. Although its antifolate properties were only modest, anticonvulsant effects were significant. During the clinical development of lamotrigine as a treatment for intractable seizures, improved mood in lamotrigine-treated patients was anecdotally reported (Jawad et al. 1989; Smith et al. 1993). Indeed, antiepileptic drugs (AEDs) have been described as a heterogeneous class of medications with a diverse range of utility in psychiatry with variable effects on mood (Muzina et al. 2005).