The Role of Melatonin in the Antipsychotic and Motor-Side Effects of Neuroleptics: A Hypothesis

Abstract

Three phenomena concerning the antipsychotic action of classic neuroleptic drugs have not been adequately explained by the dopamine hypothesis: (1) administration of neuroleptic drugs is commonly associated with an initial period of 3–6 weeks prior to demonstration of antipsychotic effects; (2) similarly, neuroleptic-induced Parkinsonism commonly emerges only after several weeks of neuroleptic therapy; (3) moreover, Parkinsonism may disappear despite continuous neuroleptic treatment. An understanding of these phenomena might shed new light into the nature of the antipsychotic actions of these agents, and hence the pathophysiology of schizophrenia.

We propose that the increase in melatonin secretion, which occurs with the initiation of neuroleptic therapy, may be responsible for the delay in the antipsychotic effects of neuroleptics and may also account for the lag in the development of drug-induced Parkinsonism as well as its disappearance. The implications of this hypothesis for the treatment of schizophrenia and the prophylaxis of drug-induced Parkinsonism are discussed.

Key Words:

• Neuroleptics
• melatonin
• dopamine
• parkinsonism