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Despite the fact that the circadian variations in the density of striatal dopaminergic D2 receptors are well documented, there are few reports concerning whether these variations may regulate the extrapyramidal symptoms produced by antipsychotic drugs. To test this hypothesis, we selected 18 male hospitalized schizophrenic subjects, who had been treated for 2 wk with 10 mg haloperidol three times a day. The extrapyramidal symptoms were evaluated 1 h after each haloperidol administration (e.g. 09:00, 14:00 and 19:00 hours). The diurnal profiles of haloperidol-induced extrapyramidal symptoms showed that akathisia and dystonia were milder in the morning and increased in severity during the night. However, Parkinsonian symptoms were more severe during the morning evaluations than during the evening tests. The difference in the diurnal pattern of the haloperidol-induced side-effects, suggests that receptor-related mechanisms with a different circadian profile contribute to the induction of the extrapyramidal symptoms.

Diurnal variations of extrapyramidal symptoms induced by haloperidol in schizophrenic subjects