PROBABLE HEPATIC ALLERGY TO CHLORPROMAZINE AND DELIBERATE DESENSITIZATION

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Abstract
During the first month of daily administration of chlorpromazine, anicteric hepatic dysfunction may develop in as much as 50% of a group of patients. Its onset is manifested by hepatocellular derangement, as reflected by increased bromsulfalein retention and serum transaminase. In almost all cases, dysfunction spontaneously subsides during continued uninterrupted administration of the drug. In 1-2% it progresses to frank jaundice. In the development of hepatic dysfunction due to chlorpromazine, although the presence of circulating antibody could not be demonstrated by skin tests, clinical data were considered to fulfil the following criteria for an allergic reaction: immunizing event, latent period, accelerated reproduction of reaction upon re-exposure to a small challenging dose, specificity, and deliberate desensitization. Three weeks to 40 months after chlorpromazine had been discontinued in 17 patients because of icteric or symptomatic anicteric hepatic dysfunction, reingestion of the drug provoked recurrence of dysfunction in 13 within 24 to 48 hours - an incidence of 76%. Deliberate hepatic desensitization to chlorpromazine was attempted and achieved in 10 cases. The drug has been continued as long as 3 years without adverse effect upon the liver, the daily dosages equalling or exceeding those administered before the original bouts of dysfunction. A method of deliberate desensitization is described. Large doses of synthetic adrenocortical hormone, prophylactically administered, partially inhibit hepatic response to a small challenge dose of chlorpromazine. Large doses of the hormone, therapeutically administered after jaundice has been established, fail to alter the natural course of the disorder. It is suggested that the prophylactic effect of the hormone is due to depression of antibody synthesis and the lack of therapeutic effect to its inability to prevent union of antigen and antibody.

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