Psychoactive Agents, Seizure Production, and Sudden Death in Epilepsy

Abstract

Major tranquilizers as well as antidepressant agents have been associated with clinical seizures in patients administered these agents. The incidence of such seizures is generally low when these drugs are administered in therapeutic doses. However, administration of large doses of these agents has been associated with many cases of convulsion production. The effects that these drugs have on animal models of epilepsy have been examined. It appears that the phenothiazines act as convulsant agents at lower doses, whereas, at higher doses, they act as anticonvulsant drugs. Antidepressants, on the other hand, appear to exert an anticonvulsant effect at low doses and convulsant effects at high doses. The mechanism by which these agents alter the seizure threshold is not yet known. Clinically, drugs of lower seizure production potential should be substituted for those drugs with greater potential in treating epileptic patients for psychiatric ailments. The problem of sudden death in epileptic patients is one that must be confronted. Sudden death has most frequently been attributed to autonomic dysfunction and cardiac arrhythmia in these patients. The contribution of stress in sudden death production also must be taken into account. In addition, some psychoactive agents have been associated with sudden death as well as cardiac arrhythmia and seizure production. Thus, in light of the possible additivity of the factors involved in the production of sudden death, the administration of a psychoactive agent to an epileptic patient should be approached with caution. Those agents that do not alter cardiac rhythm or seizure threshold should be administered if a psychoactive agent is deemed necessary for the management of psychiatric illness in the epileptic patient.

Clinical Pharmacology: Drugs as a Benefit and/or Risk in Sudden Unexpected Death in Epilepsy?

“…49 Animal studies exploring the contribution of the autonomic nervous system versus the direct drug action on the heart of phenothiazines and cocaine emphasized the latter as the important contributing factor. [50][51][52][53][54] Confirmation of findings using a second animal model strengthens conclusions made from data obtained in a given experimental animal model such as the cat model developed to study autonomic parameters associated with epileptogenic activity. [55][56][57][58][59] The similarity of the function of the pig heart to the human heart provided a particularly appropriate animal model to confirm in a second species the autonomic neural dysfunction associated with epileptogenic activity in the cat.…”

Effects of chronic haloperidol treatment on amygdaloid seizure generation in cats

“…Low frequency kindling has a great advantage in assessing seizure generating threshold and the severity of triggered seizures quantitatively, simultaneously and chronologically. Haloperidol, a potent antipsychotic agent, is known to have a proconvulsant action in clinical and experimental observations Lipka and Lathers 1987). However, little is known about chronological changes in the effect of chronic haloperidol treatment on seizure generation, because no adequate experimental model of epilepsy has been developed.…”

Clinical Features, Pathogenesis and Management of Drug-Induced Seizures

“…Agents with a high seizure potential (e.g. chlorpromazine, promazine, perphenazine) should be avoided in favour of drugs with fewer convulsant properties; the dose should always be increased slowly (Lipka & Lathers 1987). Itil and Soldatos (1980) have given specific recommendations for patients in whom abnormal EEG findings are observed during psychotropic drug treatment (fig.…”