Antiepileptic drugs (AEDs) are commonly prescribed for nonepileptic conditions, including
migraine headache, chronic
neuropathic pain,
mood disorders,
schizophrenia and various neuromuscular syndromes. In many of these conditions, as in
epilepsy, the drugs act by modifying the excitability of nerve (or muscle) through effects on voltage-gated
sodium and
calcium channels or by promoting inhibition mediated by
gamma-aminobutyric acid (
GABA) A receptors. In
neuropathic pain, chronic nerve injury is associated with the redistribution and altered subunit compositions of
sodium and
calcium channels that predispose neurons in sensory pathways to fire spontaneously or at inappropriately high frequencies, often from ectopic sites. AEDs may counteract this abnormal activity by selectively affecting
pain-specific firing; for example, many AEDs suppress high-frequency action potentials by blocking voltage-activated
sodium channels in a use-dependent fashion. Alternatively, AEDs may specifically target pathological channels; for example,
gabapentin is a
ligand of alpha2delta voltage-activated
calcium channel subunits that are overexpressed in sensory neurons after nerve injury. Emerging evidence suggests that effects on signaling pathways that regulate neuronal plasticity and survival may be
a factor in the delayed clinical efficacy of AEDs in some neuropsychiatric conditions, including bipolar
affective disorder.