Elsevier

Biological Psychiatry

Volume 46, Issue 1, July 1999, Pages 141-143
Biological Psychiatry

Brief Reports
Olanzapine acute administration in schizophrenic patients increases delta sleep and sleep efficiency

https://doi.org/10.1016/S0006-3223(98)00372-2Get rights and content

Abstract

Background: A delta sleep deficit has been observed in schizophrenic patients. Olanzapine is a novel atypical antipsychotic agent with affinity at dopaminergic, serotonergic, muscarinic, adrenergic and histaminergic binding sites. The present study was designed to analyze a sleep promoting effect reported for olanzapine.

Methods: Twenty schizophrenic patients (DSM-IV) were studied, who were drug free and inpatients. Patients slept for 5 consecutive nights in the sleep unit as follows: one acclimatization night; two baseline nights (the first for sleep disorder screenings); and two olanzapine nights (10 mg olanzapine, one hour before sleep onset).

Results: Sleep continuity variables and total sleep time showed an overall improvement with olanzapine. Waking time was reduced since the first night of olanzapine administration. The main sleep architecture changes were: reduction in sleep stage 1, while sleep stage 2 and delta were significantly enhanced. Rapid eye movement density was also increased by the second olanzapine night.

Conclusions: Total sleep improvement was due to the increase in sleep stages 2 and delta sleep. This may be related to serotonergic antagonistic properties of olanzapine. Olanzapine seems to have a sleep promoting effect in schizophrenic patients.

Introduction

Several polysomnographic abnormalities seems to occur consistently in schizophrenic patients: impaired sleep continuity and decreased total sleep time, less amount of delta sleep, and reduced rapid eye movement (REM) sleep latency and defective REM sleep rebound following REM sleep deprivation (Keshavan et al 1990).

Decrease in delta sleep has been suggested to be the prevailing alteration in the sleep of schizophrenic patients, to be stable across nights, and to represent an abnormality of trait like character (Benson and Zarcone 1989, Keshavan et al 19902; Benson et al 1996). Also, there is some correlation between the decrease in delta sleep and ventricle size, in schizophrenic patients (Lauer and Krieg 1998).

Olanzapine is a novel antipsychotic displaying nanomolar affinity at dopaminergic D1–D4, serotonergic (5–HT 2,3,6); cholinergic, muscarinic (subtypes 1–5), adrenergic (α1), and histaminergic (H1) binding sites (Bymaster et al 1996). Also olanzapine may have some interaction with glutamatergic mechanisms, that is antagonic to phencyclidine or MK–801 in inducing behavior modeling schizophrenia (Corbett et al 1995). Because there are some anecdotal comments about the sleep promoting effect of olanzapine in schizophrenic patient, we decided to study the effects of this new antipsychotic drug in the sleep of schizophrenic patients.

Section snippets

Methods and materials

Twenty schizophrenic patients were studied, 11 females, 9 males (average age: 33.6 ± 10.7 years), diagnosed after a Structured Clinical Interview for DSM-IV (SCID DSM-IV). They were drug free at least 2 weeks before entering the study, did not have antecedents of drug addiction other than nicotine, and none of the patients were on depot antipsychotics before the study. After the procedure had been fully explained, informed consent was obtained from each participant before the study began. All

Results

Twenty schizophrenic patients were studied. Ten of them were paranoid, eight undifferentiated, one catatonic and one disorganized.

Sleep variables of the twenty schizophrenic patients can be seen in Table 1. Sleep continuity variables and total sleep time (TST) had an overall improvement with olanzapine. Waking time was reduced since the first olanzapine administration (one-way ANOVA: F = 7.77, p< .001) while TST had a significant increase during the two nights with olanzapine (one-way ANOVA: F

Discussion

The major finding of the present study was an overall increase in TST with significant increase in delta sleep and sleep stage 2 since the first olanzapine night. Also there were no changes in REM sleep variables other than REM density.

Four of the twenty patients had no detectable delta sleep at all, but even in these patients there was a delta sleep enhancement. The increase in delta sleep could be related to the antagonistic properties of olanzapine on 5–HT2 serotonergic receptors.

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