Lower CSF orexin A (hypocretin-1) levels in patients with schizophrenia treated with haloperidol compared to unmedicated subjects

Hypothalamic orexins (hypocretins) regulate sleep, arousal and appetite.¹ Interactions between the dopaminergic and orexinergic systems have been suggested², but so far the effects of drugs targeting dopaminergic neurotransmission on orexin production in humans are unknown. To investigate whether and how antipsychotic drugs affect orexin production in humans, we studied cerebrospinal fluid (CSF) levels of orexin A in patients suffering from schizophrenia treated with an antipsychotic drug (APD) compared to CSF levels of orexin A in untreated patients with schizophrenia. Twenty-seven inpatients suffering from a schizophrenic [n=25] or schizoaffective disorder [n=2] were included.

We found reduced cerebrospinal orexin-A levels in patients with schizophrenia taking the anti-dopaminergic drug haloperidol compared to untreated patients, suggesting that some antipsychotic drugs might affect arousal and sleep regulation through the orexinergic systems.

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