Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT2C receptors in vivo

Sharpley, A L; Vassallo, C M; Cowen, Philip J.

doi:10.1016/s0006-3223(99)00273-5

Cited by 126 publications

(85 citation statements)

References 16 publications

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“…Significant increases in the average duration of sleep cycles and in both NREM and REM periods, mainly in the former, were also obtained. Results on sleep initiation and maintenance measures, as well as on SWS, are in concordance with previous reports where olanzapine was found to improve sleep continuity and produce dose-related SWS increases in schizophrenic (Salin-Pascual et al 2004) and healthy volunteers (Sharpley et al 2000;Lindberg et al 2002). Olanzapine is a potent 5-HT 2A/2C antagonist, and studies in humans and animals have shown that 5-HT 2A/2C receptors, primarily 5-HT 2C , are involved in the regulation of SWS (Sharpley et al 1994).…”

Section: Discussionsupporting

confidence: 91%

“…However, data on REM are far from consistent. In these earlier studies significances were obtained only at doses of 10 mg(not at 5 mg) (Sharpley et al 2000) and only in the subgroup of female participants (Lindberg et al 2002). In addition, medication was received in the evening in both studies in contrast with the current investigation where treatment was administered in the morning.…”

Section: Discussionmentioning

confidence: 58%

“…Significant distinct changes on sleep were observed after going to bed 15 h after drug administration. Although the neuroleptic's effects of sleep seem well documented, to date, there are only two controlled studies in healthy subjects after olanzapine (Sharpley et al 2000;Lindberg et al 2002), one controlled study after risperidone (Sharpley et al 2003), and none after haloperidol. The effects of these drugs on sleep have not been evaluated previously after morning administration, and only in one study after olanzapine have the data been analysed using EEG spectral power (Lindberg et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, it has been calculated that the 50% increase in SWS observed after olanzapine (5 mg) corresponds to a central occupancy of 5-HT 2C receptors of at least 70%. On the other hand, the blockade of histamine-H 1 receptors and alpha 1 adrenoreceptors has also been proposed as a possible mechanism underlying some of the hypnotic effects of olanzapine such as the decrease in sleep latency onset (Sharpley et al 2000) and wake time (Sharpley et al 2000;Lindberg et al 2002;Salin-Pascual et al 2004). Regarding the results on REM variables, in the present study we observed an increase in REM sleep and a non-significant reduction in REM latency, in clear contrast with the decrease in REM percentage commonly reported after olanzapine intake (Sharpley et al 2000; Lindberg et al 2002).…”

Section: Discussionmentioning

confidence: 99%

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Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers

et al. 2007

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Objectives To compare the effects of typical and atypical antipsychotic drugs on sleep activity and subjective sleep quality. Design Randomised, double-blind, placebo-controlled, four-period cross-over, clinical trial was used to evaluate the effects of active treatments on objective and subjective sleep variables. Setting Sleep laboratory evaluation. Participants Twenty healthy young volunteers, both sexes. Interventions Single oral morning administrations of olanzapine 5 mg, risperidone 1 mg, haloperidol 3 mg and placebo. Measurements and results Five polysomnographic nights were evaluated: one control night and one after each intervention. Significant increase in total sleep time, sleep efficiency, slow wave sleep (SWS) and rapid eye movement (REM) sleep with decreases in wake time were observed after olanzapine. Decreases in wake time, REM sleep and stage shifts together with increases in stage 2 were obtained after risperidone. Haloperidol showed only a tendency to increase sleep efficiency and stage 2 and to decrease wake time. Olanzapine showed decreases in power density in frequencies higher than 10 Hz during all sleep stages and in frequencies lower than 5 Hz range in SWS; decreases in the dynamics of spindle frequency activity (SFA) in the second and fourth non-rapid eye movement (NREM) episodes were also obtained. Risperidone presented increases in the 3.6-10.8 Hz frequency range in NREM sleep stages and in stage 2. Haloperidol also showed increases in NREM sleep stages and in stage 2, but these were in frequencies higher than 10 Hz, with increases in the dynamics of SFA in the first NREM episode. Only a significant improvement in subjective sleep quality was observed after olanzapine. Conclusions Antipsychotics showed different sleep changes as their neurochemical profiles were distinct. These changes were observed even when the drug was administered 15 h before going to bed.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers

et al. 2007

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“…2.0. The power spectrum densities, integrated and averaged, could be divided into 4 frequency areas: delta wave (0.5 -4 Hz), theta wave (4 -8 Hz), alpha wave (8 -13 Hz), and beta wave (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Delta activity (%) and beta activity (%) were calculated using following equation: Delta (beta) activity (%) = [delta (beta) wave power density in the drug administration period] / [delta (beta) wave power density in vehicle administration period in each animal] × 100.…”

Section: Sleep-wake State Analysismentioning

confidence: 99%

Effects of Some Antipsychotics and a Benzodiazepine Hypnotic on the Sleep-Wake Pattern in an Animal Model of Schizophrenia

2009

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Abstract. We studied the effects of antipsychotics and a hypnotic on sleep disturbance in schizophrenia using an animal model of the disease. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalograph for 6 h (10:00 -16:00). SleepSign ver. 2.0 was used for EEG and EMG analysis. Haloperidol and olanzapine had an antagonizing effect on the increases in sleep latency and total awake time and the decrease in total non-rapid eye movement (NREM) sleep time induced by MK-801. Olanzapine also antagonized the decrease in total rapid eye movement (REM) sleep time induced by MK-801. Aripiprazole antagonized only the increase in sleep latency induced by MK-801, whereas, risperidone, quetiapine, and flunitrazepam had no effect in the changes of sleep-wake pattern induced by MK-801. Olanzapine increased delta activity and decreased beta activity during NREM sleep. In contrast, flunitrazepam had an opposite effect. It was clarified that haloperidol and olanzapine were effective for decrease of sleep time in this animal model of schizophrenia. In addition, aripiprazole showed a sleep-inducing effect in schizophrenia model rat. On the other hand, flunitrazepam showed no beneficial effect on sleep disturbance in schizophrenia model rat.

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The sleep effects of lurasidone: a placebo‐controlled cross‐over study using a 4‐h phase‐advance model of transient insomnia

Krystal

Zammit

2016

Human Psychopharmacology

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Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT2C receptors in vivo

Cited by 126 publications

References 16 publications

Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers

Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers

Effects of Some Antipsychotics and a Benzodiazepine Hypnotic on the Sleep-Wake Pattern in an Animal Model of Schizophrenia

The sleep effects of lurasidone: a placebo‐controlled cross‐over study using a 4‐h phase‐advance model of transient insomnia

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