Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers
- 319 Downloads
To compare the effects of typical and atypical antipsychotic drugs on sleep activity and subjective sleep quality.
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.
Sleep laboratory evaluation.
Twenty healthy young volunteers, both sexes.
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.
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.
KeywordsAntipsychotics Polysomnography Spectral analysis Subjective evaluations Healthy volunteers Single morning oral intake
- Barbanoj MJ, Grasa E, Morte A, Romero S, Clos S, Giménez S, Benito Ll, Yritia M, Pérez V, Anderer P (2004) Topographic EEG changes after single oral doses of atypical neuroleptics with different pharmacological profile in healthy young subjects (abstract). 13th meeting of the IPEG (International Pharmaco–EEG Society), Amberes, Belgium (8–12 September)Google Scholar
- Borbély AA, Mattmann P, Loepfe M, Strauch I, Lehmann D (1983) Effect of benzodiazepine hypnotics on all-night sleep EEG spectra. Hum Neurobiol 4:189–194Google Scholar
- Miyamoto S, Duncan GE, Goff DC, Lieberman JA (2002) Therapeutics of schizophrenia. In: Davis KL, Charney D, Coyle JT, Nemeroff C (eds) American College of Neuropsychopharmacology: the fifth generation of progress. Lippincott, Williams and Wilkins, Philadelphia, PA, pp 775–807Google Scholar
- Pace-Schott EF, Hobson JA (2002) Basic mechanisms of sleep: new evidence on the neuroanatomy and neuromodulation of the NREM–REM cycle. In: Davis KL, Charney D, Coyle JT, Nemeroff C (eds) American College of Neuropsychopharmacology: the fifth generation of progress. Lippincott, Williams and Wilkins, Philadelphia, PA, pp 1859–1877Google Scholar
- Rechtschaffen A, Kales A (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. U.S. Government Printing Office, Washington, DCGoogle Scholar
- Saletu B, Wessely P, Grünberger J, Schultes M (1987a). Erste klinische Erfahrungen mit einem neuen schlafanstossenden Benzodiacepin Cinolazepam mittels eines Selbstbeurteilungsbogens für Schalf—und Aufwachqualität (SSA). Neuropsychiatrie 1:169–176Google Scholar
- Tandon R (1998) Antipsychotic agents. In: Klein DF, Rowland LP (eds) Current psychotherapeutic drugs. Brunner/Mazel Publishers, New York, pp 120–154Google Scholar
- Warrington SJ (1997) Ethical aspects of research in healthy volunteers. In: O’Grady J, Joubert PH (eds) Handbook of phase I/II clinical drug trials. CRS Press, Boca Raton, pp 103–110Google Scholar