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Sleep Disturbances in Patients with Schizophrenia

Impact and Effect of Antipsychotics

Abstract

Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Disturbed sleep can be found in 30–80% of schizophrenic patients, depending on the degree of psychotic symptomatology. Measured by polysomnography, reduced sleep efficiency and total sleep time, as well as increased sleep latency, are found in most patients with schizophrenia and appear to be an important part of the pathophysiology of this disorder. Some studies also reported alterations of stage 2 sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep variables, i.e. reduced REM latency and REM density. A number of sleep parameters, such as the amount of SWS and the REM latency, are significantly correlated to clinical variables, including severity of illness, positive symptoms, negative symptoms, outcome, neurocognitive impairment and brain structure.

Concerning specific sleep disorders, there is some evidence that schizophrenic patients carry a higher risk of experiencing a sleep-related breathing disorder, especially those demonstrating the known risk factors, including being overweight but also long-term use of antipsychotics. However, it is still unclear whether periodic leg movements in sleep or restless legs syndrome (RLS) are found with a higher or lower prevalence in schizophrenic patients than in healthy controls.

There are no consistent effects of first-generation antipsychotics on measuresof sleep continuity and sleep structure, including the percentage of sleep stages or sleep and REM latency in healthy controls. In contrast to first-generation antipsychotics, the studied atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, ziprasidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity, with an increase in either total sleep time (TST) or sleep efficiency, and individually varying effects on other sleep parameters, such as an increase in REM latency observed for olanzapine, quetiapine and ziprasidone, and an increase in SWS documented for olanzapine and ziprasidone in healthy subjects.

The treatment of schizophrenic patients with first-generation antipsychotics is consistently associated with an increase in TST and sleep efficiency, and mostly an increase in REM latency, whereas the influence on specific sleep stages is more variable. On the other hand, withdrawal of such treatment is followed by a change in sleep structure mainly in the opposite direction, indicating a deterioration of sleep quality. On the background of the rather inconsistent effects of first-generation antipsychotics observed in healthy subjects, it appears possible that the high-potency drugs exert their effects on sleep in schizophrenic patients, for the most part, in an indirect way by suppressing stressful psychotic symptomatology. In contrast, the available data concerning second-generation antipsychotics (clozapine, olanzapine, risperidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity in patients and healthy subjects, with an increase in TST and sleep efficiency or a decrease in wakefulness. Additionally, clozapine and olanzapine demonstrate comparable influences on other sleep variables, such as SWS or REM density, in controls and schizophrenic patients. Possibly, the effects of second-generation antipsychotics observed on sleep in healthy subjects and schizophrenic patients might involve the action of these drugs on symptomatology, such as depression, cognitive impairment, and negative and positive symptoms.

Specific sleep disorders, such as RLS, sleep-related breathing disorders, night-eating syndrome, somnambulism and rhythm disorders have been described as possible adverse effects of antipsychotics and should be considered in the differential diagnosis of disturbed or unrestful sleep in this population.

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References

  1. Doi Y, Minowa M, Uchiyama M, et al. Psychometric assessment of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in psychiatric disordered and control subjects. Psychiatry Res 2000 Dec 27; 97(2-3): 165–72

    PubMed  CAS  Google Scholar 

  2. Ritsner M, Kurs R, Ponizovsky A, et al. Perceived quality of life in schizophrenia: relationships to sleep quality. Qual Life Res May 2004; 13(4): 783–91

    Google Scholar 

  3. Hofstetter JR, Lysaker PH, Mayeda AR. Quality of sleep in patients with schizophrenia is associated with quality of life and coping. BMC Psychiatry 2005; 5(1): 13 [online]. Available from URL: http://www.biomedcentral.eom/1471-244X/5/13 [Accessed 2008 Sep 23]

    PubMed  Google Scholar 

  4. Donlon PT, Blacker KH. Clinical recognition of early schizophrenic decompensation. Dis Nerv Syst Jun 1975; 36(6): 323–7

    CAS  Google Scholar 

  5. Herz MI, Melville C. Relapse in schizophrenia. Am J Psychiatry Jul 1980; 137(7): 801–5

    CAS  Google Scholar 

  6. van Kämmen DP, van Kämmen WB, Peters JL, et al. CSF MHPG, sleep and psychosis in schizophrenia. Clin Neuropharmacol 1986; 9Suppl. 4: 575–7

    Google Scholar 

  7. Kumar S, Thara R, Rajkumar S. Coping with symptoms of relapse in schizophrenia. Eur Arch Psychiatry Neurol Sci 1989; 239(3): 213–5

    PubMed  CAS  Google Scholar 

  8. Jorgensen P. Schizophrenic delusions: the detection of warning signals. Schizophr Res 1998 Jun 22; 32(1): 17–22

    PubMed  CAS  Google Scholar 

  9. Detre T. On the psychodynamics and the ego psychology of the depressive illnesses: sleep disorder and psychosis. Can Psychiatr Assoc J 1966; 11 Spec Suppl.: S169–77

    Google Scholar 

  10. Sweetwood HL, Kripke DF, Grant I, et al. Sleep disorder and psychobiological symptomatology in male psychiatric outpatients and male nonpatients. Psychosom Med 1976 Nov–Dec; 38(6): 373–8

    PubMed  CAS  Google Scholar 

  11. Haffmans PM, Hoencamp E, Knegtering HJ, et al. Sleep disturbance in schizophrenia. Br J Psychiatry 1994 Nov; 165(5): 697–8

    PubMed  CAS  Google Scholar 

  12. Serretti A, Mandelli L, Lattuada E, et al. Depressive syndrome in major psychoses: a study on 1351 subjects. Psychiatry Res 2004 Jun 30; 127(1-2): 85–99

    PubMed  Google Scholar 

  13. Royuela A, Macias JA, Gil-Verona JA, et al. Sleep in schizophrenia: a preliminary study using the Pittsburgh Sleep Quality Index. Neurobiol Sleep Wakefulness Cycle 2002; 2(2): 37–9

    Google Scholar 

  14. Aserinsky E, Kleitman N. Regularly occuring periods of eye motility, and concomitant phenomena, during sleep. Science 1953; 118: 273–4

    PubMed  CAS  Google Scholar 

  15. Benca RM, Obermeyer WH, Thisted RA, et al. Sleep and psychiatric disorders: a meta-analysis. Arch Gen Psychiatry 1992; 49(8): 651–68

    PubMed  CAS  Google Scholar 

  16. Chouinard S, Poulin J, Stip E, et al. Sleep in untreated patients with schizophrenia: a meta-analysis. Schizophr Bull 2004; 30(4): 957–67

    PubMed  Google Scholar 

  17. Salin-Pascual RJ, Herrera-Estrella M, Galicia-Polo L, et al. Low delta sleep predicted a good clinical response to olanzapine administration in schizophrenic patients. Rev Invest Clin 2004 May–Jun; 56(3): 345–50

    PubMed  CAS  Google Scholar 

  18. Tekell JL, Hoffmann R, Hendrickse W, et al. High frequency EEG activity during sleep: characteristics in schizophrenia and depression. Clin EEG Neurosci 2005 Jan; 36(1): 25–35

    PubMed  Google Scholar 

  19. Yang C, Winkelman JW. Clinical significance of sleep EEG abnormalities in chronic schizophrenia. Schizophr Res 2006 Feb 28; 82(2-3): 251–60

    PubMed  Google Scholar 

  20. Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Washington, DC: United States Government Printing Office, 1968

    Google Scholar 

  21. Navarro JF, Davila G. Psicopatologia y sueno: I. esquizofrenia. Psicologiá Conductal 1998; 6(1): 49–62

    Google Scholar 

  22. Monti JM, Monti D. Sleep disturbance in schizophrenia. Int Rev Psychiatry 2005 Aug; 17(4): 247–53

    PubMed  Google Scholar 

  23. Benson KL. Sleep in schizophrenia: impairments, correlates, and treatment. Psychiatr Clin North Am 2006 Dec; 29(4): 1033–45

    PubMed  Google Scholar 

  24. Tandon R, Shipley JE, Taylor S, et al. Electroencephalographic sleep abnormalities in schizophrenia: relationship to positive/ negative symptoms and prior neuroleptic treatment. Arch Gen Psychiatry Mar 1992; 49(3): 185–94

    CAS  Google Scholar 

  25. Lauer CJ, Schreiber W, Pollmacher T, et al. Sleep in schizophrenia: a polysomnographic study on drug-naive patients. Neuropsychopharmacol 1997 Jan; 16(1): 51–60

    CAS  Google Scholar 

  26. Keshavan MS, Reynolds CF, Miewald MJ, et al. Delta sleep deficits in schizophrenia: evidence from automated analyses of sleep data. Arch Gen Psychiatry 1998; 55(5): 443–8

    PubMed  CAS  Google Scholar 

  27. Gaillard JM, Iorio G, Campajola P, et al. Temporal organisation of sleep in schizophrenics and patients with obsessive-compulsive disorder. In: Saletu B, Perris C, editors. Neurophysiological correlates of mental disorders. 5th International Symposium on Clinical Neurophysiological Aspects of Psychopatho-logical Conditions; 1983 Jul 9–10; Vienna. Vol.15. Basel: Karger, 1984

    Google Scholar 

  28. Kempenaers C, Kerkhofs M, Linkowski P, et al. Sleep EEG variables in young schizophrenic and depressive patients. Biol Psychiatry 1988; 24(7): 833–8

    PubMed  CAS  Google Scholar 

  29. Hoffmann R, Hendrickse W, Rush AJ, et al. Slow-wave activity during non-REM sleep in men with schizophrenia and major depressive disorders. Psychiatry Res 2000; 95(3): 215–25

    PubMed  CAS  Google Scholar 

  30. Keshavan MS, Reynolds III CF, Ganguli R, et al. EEG sleep in familial subgroups of schizophrenia [abstract]. Sleep Res 1990; 19: 330

    Google Scholar 

  31. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr-Bull 1987; 13(2): 261–76

    PubMed  CAS  Google Scholar 

  32. Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10: 779–812

    Google Scholar 

  33. Keshavan MS, Reynolds III CF, Ganguli R, et al. Electroen-cephalographic sleep and cerebral morphology in functional psychoses: a preliminary study with computed tomography. Psychiatry Res 1991 Dec; 39(3): 293–301

    PubMed  CAS  Google Scholar 

  34. Thaker GK, Wagman AM, Tamminga CA. Sleep polygraphy in schizophrenia: methodological issues. Biol Psychiatry 1990 Aug 1; 28(3): 240–6

    PubMed  CAS  Google Scholar 

  35. Taylor SF, Tandon R, Shipley JE, et al. Effect of neuroleptic treatment on polysomnographic measures in schizophrenia. Biol Psychiatry 1991 Nov 1; 30(9): 904–12

    PubMed  CAS  Google Scholar 

  36. Poulin J, Daoust AM, Forest G, et al. Sleep architecture and its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia. Schizophr Res 2003 Jul 1; 62(1-2): 147–53

    PubMed  Google Scholar 

  37. Neylan TC, van Kammen DP, Kelley ME, et al. Sleep in schizophrenic patients on and off haloperidol therapy: clinically stable vs relapsed patients. Arch Gen Psychiatry Aug 1992; 49(8): 643–9

    CAS  Google Scholar 

  38. Feinberg I, Heller N, Steinberg HR, et al. The relationship of sleep disturbance to behavior pathology in a group of schizophrenic patients. Compr Psychiatry 1965; 6(6): 374–80

    PubMed  CAS  Google Scholar 

  39. Feinberg I, Koresko RL, Gottlieb F. Further observations on electrophysiological sleep patterns in schizophrenia. Compr Psychiatry 1965; 6: 21–4

    PubMed  CAS  Google Scholar 

  40. Rotenberg VS, Hadjez J, Indursky P, et al. Eye movements density in positive and negative schizophrenia. Homeostasis 1997; 38: 97–102

    Google Scholar 

  41. Benson KL, Zarcone Jr VP. Rapid eye movement sleep eye movements in schizophrenia and depression. Arch Gen Psychiatry 1993; 50(6): 474–82

    PubMed  CAS  Google Scholar 

  42. Zarcone VP, Benson KL. BPRS symptom factors and sleep variables in schizophrenia. Psychiatry Res 1997 Feb 7; 66(2-3): 111–20

    PubMed  CAS  Google Scholar 

  43. Ganguli R, Reynolds III CF, Kupfer DJ. Electroencepha-lographic sleep in young, never-medicated schizophrenics: a comparison with delusional and nondelusional depressives and with healthy controls. Arch Gen Psychiatry 1987; 44(1): 36–44

    PubMed  CAS  Google Scholar 

  44. van Kammen DP, van Kammen WB, Peters J, et al. Decreased slow-wave sleep and enlarged lateral ventricles in schizophrenia. Neuropsychopharmacol 1988 Dec; 1(4): 265–71

    Google Scholar 

  45. Tandon R, DeQuardo JR, Taylor SF, et al. Phasic and enduring negative symptoms in schizophrenia: biological markers and relationship to outcome. Schizophr Res 2000; 45(3): 191–201

    PubMed  CAS  Google Scholar 

  46. Keshavan MS, Pettegrew JW, Reynolds III CF, et al. Biological correlates of slow wave sleep deficits in functional psychoses: 31P-magnetic resonance spectroscopy. Psychiatry Res 1995 Jul 28; 57(2): 91–100

    PubMed  CAS  Google Scholar 

  47. Keshavan MS, Miewald J, Haas G, et al. Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders. J Psychiatr Res 1995 Jul–Aug; 29(4): 303–14

    PubMed  CAS  Google Scholar 

  48. Kato M, Kajimura N, Okuma T, et al. Association between delta waves during sleep and negative symptoms in schizophrenia: pharmaco-eeg studies by using structurally different hypnotics. Neuropsychobiol 1999; 39(3): 165–72

    CAS  Google Scholar 

  49. Kajimura N, Kato M, Okuma T, et al. Relationship between delta activity during all-night sleep and negative symptoms in schizophrenia: a preliminary study. Biol Psychiatry 1996 Mar 15; 39(6): 451–4

    PubMed  CAS  Google Scholar 

  50. Riemann D, Hohagen F, Krieger S, et al. Cholinergic REM induction test: muscarinic supersensitivity underlies polysomnographic findings in both depression and schizophrenia. J Psychiatr Res 1994 May–Jun; 28(3): 195–210

    PubMed  CAS  Google Scholar 

  51. Keshavan MS, Reynolds CF, Montrose D, et al. Sleep and suicidality in psychotic patients. Acta Psychiatr Scand 1994 Feb; 89(2): 122–5

    PubMed  CAS  Google Scholar 

  52. Lewis CF, Tandon R, Shipley JE, et al. Biological predictors of suicidality in schizophrenia. Acta Psychiatr Scand Dec 1996; 94(6): 416–20

    CAS  Google Scholar 

  53. Strauss JS, Carpenter WT. The prediction of outcome in schizophrenia: I. Characteristics of outcome. Arch Gen Psychiatry 1972 Dec; 27(6): 739–46

    CAS  Google Scholar 

  54. Keshavan MS, Reynolds CF, Miewald J, et al. Slow-wave sleep deficits and outcome in schizophrenia and schizoaffective disorder. Acta Psychiatr Scand 1995; 91(5): 289–92

    Google Scholar 

  55. Goldman M, Tandon R, DeQuardo JR, et al. Biological predictors of 1-year outcome in schizophrenia in males and females. Schizophr Res 1996 Aug 23; 21(2): 65–73

    PubMed  CAS  Google Scholar 

  56. Taylor SF, Tandon R, Shipley JE, et al. Sleep onset REM periods in schizophrenic patients. Biol Psychiatry 1991 Jul 15; 30(2): 205–9

    PubMed  CAS  Google Scholar 

  57. Manoach DS, Cain MS, Vangel MG, et al. A failure of sleep-dependent procedural learning in chronic, medicated schizophrenia. Biol Psychiatry 2004 Dec 15; 56(12): 951–6

    PubMed  Google Scholar 

  58. Cazzullo CL, Fornari MG, Maffei C, et al. Sleep, psychophysiological functioning and learning processes in schizophrenia. Act Nerv Super (Praha) 1977 Jul; 19Suppl. 2: 409–17

    Google Scholar 

  59. Taylor SF, Goldman RS, Tandon R, et al. Neuropsychological function and REM sleep in schizophrenic patients. Biol Psychiatry 1992; 32(6): 529–38

    PubMed  CAS  Google Scholar 

  60. Goder R, Boigs M, Braun S, et al. Impairment of visuospatial memory is associated with decreased slow wave sleep in schizophrenia. J Psychiatr Res 2004 Nov–Dec; 38(6): 591–9

    PubMed  Google Scholar 

  61. Bodizs R, Lazar AS. Schizophrenia, slow wave sleep and visuospatial memory: sleep-dependent consolidation or trait-like correlation? J Psychiatr Res 2006 Feb; 40(1): 89–90

    PubMed  Google Scholar 

  62. Göder R, Aldenhoff JB, Boigs M, et al. Delta power in sleep in relation to neuropsychological performance in healthy subjects and schizophrenia patients. J Neuropsychiatry Clin Neurosci 2006; 18(4): 529–35

    PubMed  Google Scholar 

  63. Orzack MH, Hartmann EL, Kornetsky C. The relationship between attention and slow-wave sleep in chronic schizophrenia [proceedings]. Psychopharmacol Bull 1977 Apr; 13(2): 59–61

    PubMed  CAS  Google Scholar 

  64. Forest G, Poulin J, Daoust AM, et al. Attention and non-REM sleep in neuroleptic-naive persons with schizophrenia and control participants. Psychiatry Res 2007 Jan 15; 149(1-3): 33–40

    PubMed  Google Scholar 

  65. Benson KL, Sullivan EV, Lim KO, et al. Slow wave sleep and computed tomographic measures of brain morphology in schizophrenia. Psychiatry Res 1996 Mar 29; 60(2-3): 125–34

    PubMed  CAS  Google Scholar 

  66. Lauer CJ, Krieg JC. Slow-wave sleep and ventricular size: a comparative study in schizophrenia and major depression. Biol Psychiatry 1998 Jul 15; 44(2): 121–8

    PubMed  CAS  Google Scholar 

  67. Benson KL, Zarcone Jr VP. Sleep abnormalities in schizophrenia and other psychotic disorders. Am Psychiatr Assoc Rev Psychiatry 1994; 13: 677–705

    Google Scholar 

  68. Ancoli-Israel S, Martin J, Jones DW, et al. Sleep-disordered breathing and periodic limb movements in sleep in older patients with schizophrenia. Biol Psychiatry 1999 Jun 1; 45(11): 1426–32

    PubMed  CAS  Google Scholar 

  69. Sharafkhaneh A, Giray N, Richardson P, et al. Association of psychiatric disorders and sleep apnea in a large cohort. Sleep 2005 Nov 1; 28(11): 1405–11

    PubMed  Google Scholar 

  70. Winkelman JW. Schizophrenia, obesity, and obstructive sleep apnea. J Clin Psychiatry Jan 2001; 62(1): 8–11

    CAS  Google Scholar 

  71. Takahashi KI, Shimizu T, Sugita T, et al. Prevalence of sleep-related respiratory disorders in 101 schizophrenic inpatients. Psychiatry Clin Neurosci 1998 Apr; 52(2): 229–31

    PubMed  CAS  Google Scholar 

  72. Neeper SA, Benson KL, Faull KF, et al. Periodic leg movements in schizophrenia: incidence and correlates [abstract]. Sleep Res 1992; 21: 154

    Google Scholar 

  73. Ancoli-Israel S, Kripke DF, Klauber MR, et al. Periodic limb movements in sleep in community-dwelling elderly. Sleep 1991; 14(6): 496–500

    PubMed  CAS  Google Scholar 

  74. Linden M, Thiels C. Epidemiology of prescriptions for neuroleptic drugs: tranquilizers rather than antipsychotics. Pharmacopsychiatry 2001 Jul; 34(4): 150–4

    PubMed  CAS  Google Scholar 

  75. Kanno O, Watanabe H, Kazamatsuri H. Effects of zopiclone, flunitrazepam, triazolam and levomepromazine on the transient change in sleep-wake schedule: polygraphic study, and the evaluation of sleep and daytime condition. Prog Neuropsy-chopharmacol Biol Psychiatry 1993 Mar; 17(2): 229–39

    CAS  Google Scholar 

  76. Lewis SA, Evans JI. Dose effects of chlorpromazine on human sleep. Psychopharmacologia 1969; 14(4): 342–8

    PubMed  CAS  Google Scholar 

  77. Hartmann E, Cravens J. The effects of long term administration of psychotrophic drugs on human sleep: IV. The effects of chlorpromazine. Psychopharmacologia 1973; 33(3): 203–18

    CAS  Google Scholar 

  78. Gaillard JM, Moneme A. Modification of dream content after preferential blockade of mesolimbic and mesocortical dopa-minergic systems. J Psychiatr Res 1977; 13(4): 247–56

    PubMed  CAS  Google Scholar 

  79. Kupfer DJ, Wyatt RJ, Synder F, et al. Chlorpromazine and sleep in psychiatric patients. Arch Gen Psychiatry 1971 Feb; 24(2): 185–9

    PubMed  CAS  Google Scholar 

  80. Kaplan J, Dawson S, Vaughan T, et al. Effect of prolonged chlorpromazine administration on the sleep of chronic schizophrenics. Arch Gen Psychiatry 1974; 31(1): 62–6

    PubMed  CAS  Google Scholar 

  81. Brannen JO, Jewett RE. Effects of selected phenothiazines on REM sleep in schizophrenics. Arch Gen Psychiatry 1969 Sep; 21(3): 284–90

    PubMed  CAS  Google Scholar 

  82. Adam K, Allen S, Carruthers Jones I, et al. Mesoridazine and human sleep. Br J Clin Pharmacol Feb 1976; 3(1): 157–63

    CAS  Google Scholar 

  83. Risberg AM, Risberg J, Ingvar DH. Effects of promethazine on nocturnal sleep in normal man. Psychopharmacologia 1975 Sep 17; 43(3): 279–84

    PubMed  CAS  Google Scholar 

  84. Feinberg I, Wender PH, Koresko RL, et al. Differential effects of chlorpromazine and phenobarbital on EEG sleep patterns. J Psychiatr Res 1969 Dec; 7(2): 101–9

    PubMed  CAS  Google Scholar 

  85. Gillin JC, van Kammen DP, Post R, et al. Effects of prolonged administration of pimozide on sleep-EEG patterns in psychiatric patients. Commun Psychopharmacol 1977; 1(3): 225–32

    PubMed  CAS  Google Scholar 

  86. Keshavan MS, Reynolds CF, Miewald JM, et al. A longitudinal study of EEG sleep in schizophrenia. Psychiatry Res 1996; 59(3): 203–11

    PubMed  CAS  Google Scholar 

  87. Maixner S, Tandon R, Eiser A, et al. Effects of antipsychotic treatment on polysomnographic measures in schizophrenia: a replication and extension. Am J Psychiatry 1998; 155(11): 1600–2

    PubMed  CAS  Google Scholar 

  88. Wetter TC, Lauer CJ, Gillich G, et al. The electroencepha-lographic sleep pattern in schizophrenic patients treated with clozapine or classical antipsychotic drugs. J Psychiatr Res Nov–Dec 1996; 30(6): 411–9

    CAS  Google Scholar 

  89. Clarenbach P, Prunkl R, Riegler M, et al. Effects of haloperidol on afternoon sleep and on the secretion of growth hormone in man. Neuroscience 1978; 3(3): 345–8

    PubMed  CAS  Google Scholar 

  90. Puca FM, Dammacco F, Rigillo N, et al. Increzione somato-tropinica ed EEG durante il sonno notturno dell’ adulto normale dopo pimozide. Boll Soc Ital Biol Sper 1978 Mar 15; 54(5): 460–5

    PubMed  CAS  Google Scholar 

  91. Gimenez S, Clos S, Romero S, et al. Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers. Psychopharmacology (Berl) Mar 2007; 190(4): 507–16

    CAS  Google Scholar 

  92. Lester BK, Guerrero Figueroa R. Effects of some drugs on electroencephalographic fast activity and dream time. Psychophysiology Jan 1966; 2(3): 224–36

    CAS  Google Scholar 

  93. Sagaies T, Erill S, Domino EF. Differential effects of scopolamine and chlorpromazine on REM and NREM sleep in normal male subjects. Clin Pharmacol Ther 1969 Jul–Aug; 10(4): 522–9

    Google Scholar 

  94. Lester BK, Coulter JD, Cowden LC, et al. Chlorpromazine and human sleep. Psychopharmacologia 1971; 20(3): 280–7

    PubMed  CAS  Google Scholar 

  95. Nakazawa Y, Kotorii M, Kotorii T, et al. Individual variations in response of human REM sleep to amitriptyline and haloperidol. Electroencephalogr Clin Neurophysiol Jun 1977; 42(6): 769–75

    CAS  Google Scholar 

  96. Sagaies T, Erill S. Effects of central dopaminergic blockade with primozide upon the EEG stages of sleep in man. Psychopharmacologia 1975; 41(1): 53–6

    Google Scholar 

  97. Toyoda J. The effects of chlorpromazine and imipramine on the human nocturnal sleep electroencephalogram. Folia Psychiatr Neurol Jpn 1964; 18: 198–221

    Google Scholar 

  98. Thaker GK, Wagman AM, Kirkpatrick B, et al. Alterations in sleep polygraphy after neuroleptic withdrawal: a putative supersensitive dopaminergic mechanism. Biol Psychiatry Jan 1989; 25(1): 75–86

    CAS  Google Scholar 

  99. Nofzinger EA, van Kammen DP, Gilbertson MW, et al. Electroencephalographic sleep in clinically stable schizophrenic patients: two-weeks versus six-weeks neuroleptic-free. Biol Psychiatry 1993 Jun 1-15; 33(11-12): 829–35

    PubMed  CAS  Google Scholar 

  100. Chemerinski E, Ho BC, Flaum M, et al. Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia. Compr Psychiatry Sep–Oct 2002; 43(5): 393–6

    Google Scholar 

  101. Touyz SW, Beumont PJ, Saayman GS, et al. A psychophysiological investigation of the short-term effects of clozapine upon sleep parameters of normal young adults. Biol Psychiatry 1977 Dec; 12(6): 801–22

    PubMed  CAS  Google Scholar 

  102. Sharpley AL, Vassallo CM, Cowen PJ. Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT(2C) receptors in vivo. Biol Psychiatry 2000 Mar 1; 47(5): 468–70

    PubMed  CAS  Google Scholar 

  103. Sharpley AL, Vassallo CM, Pooley EC, et al. Allelic variation in the 5-HT2C receptor (HT2RC) and the increase in slow wave sleep produced by olanzapine. Psychopharmacol (Berl) 2001 Jan 1; 153(2): 271–2

    CAS  Google Scholar 

  104. Cohrs S, Rodenbeck A, Guan Z, et al. Sleep-promoting properties of quetiapine in healthy subjects. Psychopharmacol (Berl) 2004; 174(3): 421–9

    CAS  Google Scholar 

  105. Cohrs S, Meier A, Neumann AC, et al. Improved sleep continuity and increased slow wave sleep and REM latency during ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy male subjects. J Clin Psychiatry 2005 Aug; 66(8): 989–96

    PubMed  CAS  Google Scholar 

  106. Hinze-Selch D, Mullington J, Orth A, et al. Effects of clozapine on sleep: a longitudinal study. Biol Psychiatry 1997; 42(4): 260–6

    PubMed  CAS  Google Scholar 

  107. Lee JH, Woo JI, Meltzer HY. Effects of clozapine on sleep measures and sleep-associated changes in growth hormone and Cortisol in patients with schizophrenia. Psychiatry Res 2001 Sep 20; 103(2-3): 157–66

    PubMed  CAS  Google Scholar 

  108. Tandon R. Effects of atypical antipsychotics on polysomno-graphic measures in schizophrenia. In: Judd LL, Saletu B, Filip V, editors. Basic and clinical science of mental and addictive disorders. Vol.167. Basel: Karger, 1997: 219–22

    Google Scholar 

  109. Salin Pascual RJ, Herrera Estrella M, Galicia Polo L, et al. Olanzapine acute administration in schizophrenic patients increases delta sleep and sleep efficiency. Biol Psychiatry 1999 Jul 1; 46(1): 141–3

    PubMed  CAS  Google Scholar 

  110. Müller MJ, Rossbach W, Mann K, et al. Subchronic effects of olanzapine on sleep EEG in schizophrenic patients with predominantly negative symptoms. Pharmacopsychiatry Jul 2004; 37(4): 157–62

    Google Scholar 

  111. Luthringer R, Staner L, Noel N, et al. A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia. Int Clin Psychopharmacol 2007 Sep; 22(5): 299–308

    PubMed  Google Scholar 

  112. Sharpley AL, Bhagwagar Z, Hafizi S, et al. Risperidone augmentation decreases rapid eye movement sleep and decreases wake in treatment-resistant depressed patients. J Clin Psychiatry Feb 2003; 64(2): 192–6

    CAS  Google Scholar 

  113. Touyz SW, Saayman GS, Zabow T. A psychophysiological investigation of the long-term effects of clozapine upon sleep patterns of normal young adults. Psychopharmacology (Berl) 1978 Jan 31; 56(1): 69–73

    CAS  Google Scholar 

  114. Rüther E, Davis L, Papousek M, et al. Pharmakologische Beeinflussung zentraler serotonerger Mechanismen am Menschen und Auswirkungen auf den Schlaf. Arzneimittelforschung 1976; 26(6): 1071–3

    PubMed  Google Scholar 

  115. Blum A, Girke W. Marked increase in REM sleep produced by a new antipsychotic compund. Clin Electoencephalogr 1973; 4(2): 80–4

    Google Scholar 

  116. Mignot E, Taheri S, Nishino S. Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders. Nat Neurosci Nov 2002; 5 Suppl.: 1071–5

    CAS  Google Scholar 

  117. Siegel JM. The neurotransmitters of sleep. J Clin Psychiatry 2004; 65Suppl. 16: 4–7

    PubMed  CAS  Google Scholar 

  118. Gerlach J, Peacock L. New antipsychotics: the present status. Int Clin Psychopharmacol Sep 1995; 10Suppl. 3: 39–48

    Google Scholar 

  119. Espana RA, Scammell TE. Sleep neurobiology for the clinician. Sleep 2004 Jun 15; 27(4): 811–20

    PubMed  Google Scholar 

  120. Cohrs S, Roher C, Jordan W, et al. The atypical antipsychotics olanzapine and quetiapine, but not haloperidol, reduce ACTH and cortisol secretion in healthy subjects. Psychopharmacol (Berl) 2006 Mar; 185(1): 11–8

    CAS  Google Scholar 

  121. Marx CE, VanDoren MJ, Duncan GE, et al. Olanzapine and clozapine increase the GABAergic neuroactive steroid allo-pregnanolone in rodents. Neuropsychopharmacol Jan 2003; 28(1): 1–13

    CAS  Google Scholar 

  122. Yamashita H, Mori K, Nagao M, et al. Effects of changing from typical to atypical antipsychotic drugs on subjective sleep quality in patients with schizophrenia in a Japanese population. J Clin Psychiatry 2004 Nov; 65(11): 1525–30

    PubMed  Google Scholar 

  123. Ekbom KA. Restless legs syndrome. Neurology 1960 Sep; 10: 868–73

    PubMed  CAS  Google Scholar 

  124. Akpinar S. Treatment of restless legs syndrome with levodopa plus benserazide [letter]. Arch Neurol 1982 Nov; 39(11): 739

    PubMed  CAS  Google Scholar 

  125. Montplaisir J, Lorrain D, Godbout R. Restless legs syndrome and periodic leg movements in sleep: the primary role of dopaminergic mechanism. Eur Neurol 1991; 31(1): 41–3

    PubMed  CAS  Google Scholar 

  126. Horiguchi J, Yamashita H, Mizuno S, et al. Nocturnal eating/ drinking syndrome and neuroleptic-induced restless legs syndrome. Int Clin Psychopharmacol 1999 Jan; 14(1): 33–6

    PubMed  CAS  Google Scholar 

  127. Staedt J, Dewes D, Danos P, et al. Can chronic neuroleptic treatment promote sleep disturbances in elderly schizophrenic patients? Int J Geriatr Psychiatry 2000 Feb; 15(2): 170–6

    PubMed  CAS  Google Scholar 

  128. Barnes TR, Braude WM. Akathisia variants and tardive dyskinesia. Arch Gen Psychiatry 1985 Sep; 42(9): 874–8

    PubMed  CAS  Google Scholar 

  129. Walters AS, Hening W, Rubinstein M, et al. A clinical and polysomnographic comparison of neuroleptic-induced akathisia and the idiopathic restless legs syndrome. Sleep 1991 Aug; 14(4): 339–45

    PubMed  CAS  Google Scholar 

  130. Lipinski JF, Hudson JI, Cunningham SL, et al. Polysomnographic characteristics of neuroleptic-induced akathisia. Clin Neuropharmacol 1991 Oct; 14(5): 413–9

    PubMed  CAS  Google Scholar 

  131. Kraus T, Schuld A, Pollmacher T. Periodic leg movements in sleep and restless legs syndrome probably caused by olanzapine. J Clin Psychopharmacol 1999 Oct; 19(5): 478–9

    PubMed  CAS  Google Scholar 

  132. Wetter TC, Brunner J, Bronisch T. Restless legs syndrome probably induced by risperidone treatment. Pharmacopsychiatry 2002 May; 35(3): 109–11

    PubMed  CAS  Google Scholar 

  133. Pinninti NR, Mago R, Townsend J, et al. Periodic restless legs syndrome associated with quetiapine use: a case report. J Clin Psychopharmacol 2005 Dec; 25(6): 617–8

    PubMed  Google Scholar 

  134. Duggal HS, Mendhekar DN. Clozapine-associated restless legs syndrome. J Clin Psychopharmacol 2007 Feb; 27(1): 89–90

    PubMed  Google Scholar 

  135. McLean AJ. The use of the dopamine-receptor partial agonist aripiprazole in the treatment of restless legs syndrome [letter]. Sleep 2004 Aug 1; 27(5): 1022

    PubMed  Google Scholar 

  136. Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999 Nov; 156(11): 1686–96

    PubMed  CAS  Google Scholar 

  137. Wirshing DA, Pierre JM, Wirshing WC. Sleep apnea associated with antipsychotic-induced obesity. J Clin Psychiatry 2002 Apr; 63(4): 369–70

    PubMed  Google Scholar 

  138. Boufidis S, Kosmidis MH, Bozikas VP, et al. Treatment outcome of obstructive sleep apnea syndrome in a patient with schizophrenia: case report. Int J Psychiatry Med 2003; 33(3): 305–10

    PubMed  Google Scholar 

  139. Lu ML, Shen WW. Sleep-related eating disorder induced by risperidone. J Clin Psychiatry 2004 Feb; 65(2): 273–4

    PubMed  Google Scholar 

  140. Paquet V, Strul J, Servais L, et al. Sleep-related eating disorder induced by olanzapine [letter]. J Clin Psychiatry 2002 Jul; 63(7): 597

    PubMed  Google Scholar 

  141. Flemenbaum A. Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage. Am J Psychiatry 1976; 133(5): 570–2

    PubMed  CAS  Google Scholar 

  142. Huapaya L. Somnambulism and bedtime medication [letter]. Am J Psychiatry 1976; 133(10): 1207

    PubMed  CAS  Google Scholar 

  143. Luchins DJ, Sherwood PM, Gillin JC, et al. Filicide during psychotropic-induced somnambulism: a case report. Am J Psychiatry 1978; 135(11): 1404–5

    PubMed  CAS  Google Scholar 

  144. Charney DS, Kales A, Soldates CR, et al. Somnambulistic-like episodes secondary to combined lithium-neuroleptic treatment. Br J Psychiatry 1979 Nov; 135: 418–24

    PubMed  CAS  Google Scholar 

  145. Kolivakis TT, Margolese HC, Beauclair L, et al. Olanzapine-induced somnambulism [letter]. Am J Psychiatry Jul 2001; 158(7): 1158

    PubMed  CAS  Google Scholar 

  146. Goldbloom D, Chouinard G. Clonazepam in the treatment of neuroleptic-induced somnambulism [letter]. Am J Psychiatry 1984 Nov; 141(11): 1486

    PubMed  CAS  Google Scholar 

  147. Wirz-Justice A, Haug HJ, Cajochen C. Disturbed circadian rest-activity cycles in schizophrenia patients: an effect of drugs? Schizophr Bull 2001; 27(3): 497–502

    PubMed  CAS  Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. Dr Cohrs has received a research grant from and served as a speaker for AstraZeneca.

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Cohrs, S. Sleep Disturbances in Patients with Schizophrenia. CNS Drugs 22, 939–962 (2008). https://doi.org/10.2165/00023210-200822110-00004

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Keywords

  • Clozapine
  • Olanzapine
  • Schizophrenic Patient
  • Ziprasidone
  • Obstructive Sleep Apnoea