Neurobehavioral syndrome induced by H2-receptor blocker withdrawal: possible role of prolactin.

Cimetidine and ranitine are histamine H2-receptor blockers widely used for the treatment of gastric hypersecretion and duodenal pathologies. They are known to induce hyperprolactinemia in humans. Forty-six patients treated with cimetidine or ranitidine who were exhibiting a neurobehavioral syndrome after withdrawal of the drugs were selected. This syndrome was associated with a drop in plasma prolactin levels. The symptoms of this syndrome were greatly improved by restoration of treatment with the same drugs and reappeared when the treatment was again suspended. This syndrome was inhibited in 36 patients by administration of domperidone (30 mg/day), a drug inducing hyperprolactinemia without crossing the blood-brain barrier, as compared with 10 control patients treated with placebo. These results suggest that the drop in prolactin levels occurring when cimetidine and ranitidine are suspended may contribute to the development of this syndrome. Also, the withdrawal of H2-receptor blockers could be included among the possible causes of some neurotic syndromes.