Carbamazepine kindled seizures

Mechanism of tolerance. The molecular events involved in the development of tolerance to carbamazepine have not been clearly identified. However, in a preclinical animal model using amygdala-kindled seizures, S. R. B. Weiss and colleagues (1995) in our laboratory have found that the variety of seizure-induced adaptive changes that usually emerge following seizures fail to do so with development of tolerance to the anticonvulsant effects of carbamazepine. The loss of these adaptive changes, such as increases in... 

Weiss SRB, Post RM, Sohn E, et al Cross tolerance between carbamazepine and valproate on amygdala-kindled seizures. Epilepsy Res 16 37-44, 1993 Weiss SRB, Clark M, Rosen JB, et al Contingent tolerance to the anticonvulsant effects of carbamazepine relationship to loss of endogenous adaptive mechanisms. Brain Res Brain Res Rev 20 305-325, 1995 Weissman MM Panic disorder impact on the quality of life. J Clin Psychiatry 52 [suppl) 6-8, 1991... 

Based on theories that mania may kindle further episodes of mania, a logical parallel with seizure disorders was drawn, since seizures can kindle more seizures. Thus, trials of several anticonvulsants, beginning with carbamazepine, have been conducted, and several are showing indications of efficacy in treating the manic phase of bipolar disorder (Table 7—1). Only valproic acid, however, is actually approved for this indication. 

Kindling may account for the lowered seizure threshold following chronic cocaine abuse. This phenomenon has been described elsewhere (e.g. in the use of carbamazepine in the treatment of mania), and occurs when small, subconvulsive doses eventually give rise to spontaneous seizures. 

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