Discussion on the Toxic Effects of Drugs Used in Neurological and Psychiatric Practice

Abstract

Drugs Used in the Management of Epilepsy It would be of some interest to know how many patients are being treated for epilepsy at any one moment, the incidence of epilepsy, very broadly defined, in Great Britain usually being considered to be about 250,000 persons. Through the kind cooperation of the Leeds Executive Council a group of general practitioners was circularized and information obtained relating to a population of about 300,000. 800 epileptic patients were reported to be under treatment, an incidence of 2-5 patients per 1,000 population. This suggests that the number of epileptics under treatment in Great Britian (population approx. 50,000,000) is about 125,000, which is perhaps only half of all epileptics. My personal figures relate to a survey of over 2,000 epileptic patients seen in the Neurological Department of the General Infirmary at Leeds, and in private practice, between the years 1948 and 1956. The dominant problems arose in connexion with the hydantoins, the bromides, primidone and the diones. In this group only two examples of barbiturate intoxication were seen, which illustrates the wide margin of safety between the therapeutic and toxic doses of the barbiturates. The hydantoins.-During the initial stages of treatment the signs and symptoms of intoxication with sodium phenytoin are the result of gastric irritation, giving rise to anorexia, nausea and vomiting, or to individual idiosyncrasy reflected in the skin by rashes which may resemble those of measles or scarlet fever. The former may be avoided by giving the drug after meals, whilst, if small doses are given initially and later increased, the incidence of dermatological complications is said not to exceed 5% (Tullidge and Fox, 1942; Symonds, 1950) and in my experience the incidence has been even less. The most important toxic phenomena are referable to dysfunction of the cerebellum with resulting dysarthria, nystagmus and ataxia, with or without disturbance of mentation and behaviour. In 31 patients symptoms and signs of this nature occurred and were of sufficient severity to warrant admission to hospital. It was possible in only 4 to incriminate overdosage and in another 3, who developed their disability within the first few days of treatment, individual hypersensitivity seemed to be the predominant factor. The greater proportion, however, had received sodium phenytoin and phenobarbitone or phemitone (Prominal) for many years in unvarying quantities and had developed evidence of toxicity for no apparent reason. This would seem to indicate that either detoxication or excretion varies from time to time in any one individual and may occasionally lead to the accumulation of an excessive quantity of phenytoin. In others it is clear that there is a very narrow margin between the therapeutic and the toxic doses, and 6 patients developed toxic symptoms after their daily intake was increased from 3 to 4j grains. More rarely the addition of primidone may provoke phenytoin toxicity although the dose of the latter drug is not altered. Mental dis...