Sensitization and Kindling Perspectives for the Course of Affective Illness: Toward a New Treatment with the Anticonvulsant Carbamazepine

Abstract

Successive episodes of affective illness often show an accelerating frequency of recurrence. Two very different preclinical models (behavioral sensitization to psychomotor stimulants and electrophysiological kindling) may be used as indirect analogies or non-homologous models for conceptualizing mechanisms underlying the progressive and evolving aspects of manic-depressive illness. These models focus on phenomena involved in the longitudinal course of illness and on novel treatment implications. Literature is reviewed on the acute and long-term effectiveness of the anti-convulsant carbamazepine, particularly in treatment of lithium-refractory bipolar illness. Potential mechanisms of carbamazepine's acute anticonvulsant and antinociceptive and delayed psychotropic actions are discussed. alpha-2 adrenergic and peripheral-type benzodiazepine receptors, and stabilization of type-2 sodium channels are likely involved in the anticonvulsant effects of carbamazepine. GABAB mechanisms are thought to be related to the antinociceptive but not anticonvulsant or psychotropic effects of carbamazepine. A large number of neurotransmitters remain candidates for the psychotropic effects and a novel animal model requiring chronic administration of carbamazepine in order to show efficacy is reported (Weiss et al., 1989). It is hoped that further understanding of the mechanism of action of the anti-convulsant agents in comparison and contrast with traditional psychotropic agents will help in generating new treatments and in uncovering the basic defects of manic-depressive illness.