Ta. Ketter et al., Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders, NEUROLOGY, 53(5), 1999, pp. S53-S67
Antiepileptic drugs (AEDs) have various mechanisms of actions and therefore
have diverse anticonvulsant, psychiatric, and adverse effect profiles. Two
global categories of AEDs are identified on the basis of their predominant
psychotropic profiles. One group has "sedating" effects in association wit
h fatigue, cognitive slowing, and weight gain, as well as possible anxiolyt
ic and antimanic effects. These actions may be related to a predominance of
potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmissio
n induced by drugs such as barbiturates, benzodiazepines, valproate, gabape
ntin, tiagabine, and vigabatrin. The other group is associated with predomi
nant attenuation of glutamate excitatory neurotransmission and has "activat
ing" effects, with activation, weight loss, and possibly anxiogenic and ant
idepressant effects. This group includes agents such as felbamate and lamot
rigine. Agents such as topiramate, with both GABAergic and antiglutamatergi
c actions, may have "mixed" profiles. Mechanisms of actions, activity in an
imal models of anxiety and depression, and clinical psychotropic effects of
AEDs in psychiatric and epilepsy patients are reviewed in relationship to
this proposed categorization. These considerations suggest the testable hyp
othesis that better psychiatric outcomes in seizure disorder patients could
be achieved by treating patients with baseline "activated" profiles (insom
nia, agitation, anxiety, racing thoughts, weight loss) with "sedating" pred
ominantly GABAergic drugs, and conversely those with baseline "sedated" or
anergic profiles (hypersomnia, fatigue, apathy, depression, sluggish cognit
ion, weight gain) with "activating" predominantly antiglutamatergic agents.
Systematic clinical investigation of more precise relationships of discret
e mechanisms of actions to psychotropic profiles of AEDs is needed to asses
s the utility of this general proposition and define exceptions to this bro
ad principle.