Schlafstörungen bei schizophrenen Erkrankungen

Zusammenfassung

Ein- und Durchschlafstörungen und Störungen der zirkadianen Rhythmik finden sich sehr häufig im Rahmen schizophrener Erkrankungen. Schlafstörungen treten als Frühzeichen der Erstmanifestation sowie des Rezidivs auf und stehen in Beziehung zu Positivsymptomen und der Desorganisation des Denkens. In der schlafpolygrafischen Untersuchung finden sich bei schizophrenen Patienten typischerweise eine verlängerte Einschlaflatenz, eine Reduktion der Schlafeffizienz und eine Reduktion des Tiefschlafs, wobei speziell die Störungen des Tiefschlafs die neokortikale Plastizität und die Kognition negativ beeinflussen können. Im klinischen Alltag finden die erheblichen Schlafstörungen oft nicht die notwendige Berücksichtigung, zumal z. B. ältere Neuroleptika wie Haloperidol sogar die zirkadiane Rhythmik und damit den Schlaf-/Wachrhythmus Schizophrener negativ beeinflussen können. In der Übersicht werden daher zum besseren Verständnis die pathophysiologischen Veränderungen des Schlafes im Rahmen schizophrener Erkrankungen und deren potenzielle Auswirkungen diskutiert. Bezüglich der Therapie werden neben psychoedukativen Bausteinen auch schlafmedizinisch sinnvolle Neuroleptikabehandlungen diskutiert. Kenntnisse über Veränderungen des Schlafes im Rahmen schizophrener Erkrankungen ermöglichen die Berücksichtigung schlafhygienischer Maßnahmen im Therapieverlauf, die unter Umständen den Behandlungsverlauf positiv beeinflussen können.

Abstract

Difficulties initiating and maintaining sleep as well as circadian rhythm disorders are very common in schizophrenia. Sleeping disorders occur as early signs of the first manifestation of illness as well as early signs of relapse. They bear a relation to positive symptoms and disorganisation of thought. Polysomnographic investigations with schizophrenic patients typically demonstrate a prolonged sleep-onset latency and a decrease in sleep efficiency and slow wave sleep. In particular, distortions of deep sleep can affect neocortical plasticity and cognition negatively. The considerable sleeping disorders are often not sufficiently taken into account in clinical routine. Particularly older antipsychotic medication like Haloperidol can affect the circadian and sleep-wake rhythms negatively. Therefore, pathophysiological changes of sleep within the scope of schizophrenic disorders and their potential implications are discussed in this outline. Regarding therapy, psychoeducative approaches are discussed as well as the administration of antipsychotic medication in accordance with the recommendations of sleep medicine professionals.

Schlüsselwörter

Schlafstörungen - Schizophrenie - zirkadianer Rhythmus - Schlafhygiene

Key words

sleep disorders - schizophrenia - circadian rhythm - sleep hygiene

Literatur

• 1 Wittchen H U, Krause P, Höfler M. et al . NISAS-2000: The „Nationwide Insomnia Screening and Awareness Study”. Prevalence and interventions in primary care.  Fortschr Med Orig. 2001;  119 (1) 9-19
• 2 Benca R M, Obermeyer W H, Thisted R A. et al . Sleep and psychiatric disorders: a meta-analysis.  Arch Gen Psychiatry. 1992;  49 651-668
• 3 Benca R M. Sleep in psychiatric disorders.  Neurol Clin. 1996;  14 (4) 739-764
• 4 Häfner H, an der Heiden W. The course of schizophrenia in the light of modern follow-up studies: the ABC and WHO studies.  Eur Arch Psychiatry Clin Neurosci. 1999;  249 (Suppl 4) 14-26
• 5 Herz M I, Melville C. Relapse in schizophrenia.  Am J Psychiatry. 1980;  137 (7) 801-805
• 6 Chemerinski E, Ho B C, Flaum M. et al . Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia.  Compr Psychiatry. 2002;  43 (5) 393-396
• 7 Kim S F, Huang A S, Snowman A M. et al . Antipsychotic drug-induced weight gain mediated by histamine H 1 receptor-linked activation of hypothalamic AMP-kinase.  Proc Natl Acad Sci U S A. 2007;  104 (9) 3456-3459
• 8 Winkelman J W. Schizophrenia, obesity, and obstructive sleep apnea.  J Clin Psychiatry. 2001;  62 (1) 8-11
• 9 Hohl-Radke F, Dewes D, Staedt J. Schlafstörungen und periodische Beinbewegungen bei Patienten mit Schizophrenien und schizoaffektiven Psychosen. Korrelation mit dem Lebensalter und mit der Dauer der Antipsychotikaeinnahme.  NeuroGer. 2006;  1 (2) 85-92
• 10 Ganguli R, Reynolds 3rd  C F, Kupfer D J. Electroencephalography 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
• 11 Jus K, Bouchard M, Jus A K. et al . Sleep EEG studies in untreated, long-term schizophrenic patients.  Arch Gen Psychiatry. 1973;  29 386-390
• 12 Lauer C J, Schreiber W, Pollmächter T. et al . Sleep in schizophrenia: a polysomnographic study on drug-naive patients.  Neuropsychopharmacology. 1997;  16 51-60
• 13 Stern M, Fram D H, Wyatt R. et al . All-night sleep studies of acute schizophrenics.  Arch Gen Psychiatry. 1969;  20 (4) 470-477
• 14 Martin J L, Jeste D V, Ancoli-Israel S. Older schizophrenia patients have more disrupted sleep and circadian rhythms than age-matched comparison subjects.  Psychiatr Res. 2005;  39 (3) 251-259
• 15 Wulff K, Joyce E, Middleton B. et al . The Suitability of actigraphy, diary data, and urinary melatonin profiles for quantitative assessment of sleep disturbances in schizophrenia: A case Report.  Chronobiology International. 2006;  23 (1&2) 485-495
• 16 Yang C, Winkelman J W. Clinical significance of sleep EEG abnormalities in chronic schizophrenia.  Schizophr Res. 2006;  82 (2 – 3) 251-260
• 17 Wulff K, Joyce E M, Middleton B. et al . Circadian activity and sleep cycle disturbances in schizophrenia patients in comparison to unemployed healthy controls.  Int J Neuropsychopharmacology. 2008;  11 (Suppl 1) 150
• 18 Deutsche Gesellschaft für Psychiatrie Psychotherapie und Nervenheilkunde .S3 Praxisleitlinien in Psychiatrie und Psychotherapie. Band 1. Behandlungsleitlinie Schizophrenie. Darmstadt; Steinkopff Verlag 2006
• 19 Tandon R, Shipley J E, Taylor S. et al . Electroencephalographic sleep abnormalities in schizophrenia. Relationship to positive/negative symptoms and prior neuroleptic treatment.  Arch Gen Psychiatry. 1992;  49 (3) 185-194
• 20 Benson K L, Faull K L, Zarcone V P. Evidence for the role of serotonin in the regulation of slow wave sleep in schizophrenia.  Sleep. 1991;  14 133-139
• 21 Salín-Pascual R J, Herrera-Estrella Jr M, Galicia-Polo L. et al . Low delta sleep predicted a good clinical response to olanzapine administration in schizophrenic patients.  Rev Invest Clin. 2004;  56 (3) 345-350
• 22 Benson K L, Sullivan E V, Lim K O. et al . Slow wave sleep and computed tomographic measures of brain morphology in schizophrenia.  Psychiatry Res. 1996;  60 25-134
• 23 Benson K L, Zarcone V P. Rapid eye movement sleep in schizophrenia and depression.  Arch Gen Psychiatry. 1993;  50 474-483
• 24 Caldwell D F, Domingo E F. Electroencephalographic and eye movement patterns during sleep in chronic schizophrenic patients.  Electroencephalogr Clin Neurophysiol. 1967;  22 (5) 414-420
• 25 Feinberg I, Braun M, Koresko R L. et al . Stage 4 sleep in schizophrenia.  Arch Gen Psychiatry. 1969;  21 (3) 262-266
• 26 Hiatt J F, Floyd T C, Katz P H. et al . Further evidence of abnormal non-rapid-eye-movement sleep in schizophrenia.  Arch Gen Psychiatry. 1985;  42 797-802
• 27 Poulin J, Daoust A M, Forest G. et al . Sleep architecture and its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia.  Schizophr Res. 2003;  62 (1 – 2) 147-153
• 28 Lauer C J, Krieg J C. Slow-wave sleep and ventricular size: Effects of antipsychotic comparative study in schizophrenia and major depression.  Psychiatry. 1998;  44 (2) 121-128
• 29 Forest G, Poulin J, Daoust A M. et al . Attention and non-REM sleep in neuroleptic-naive persons with schizophrenia and control participants.  Psychiatry Res. 2007 15;  149(1–3) 33-40
• 30 Baldessarini R J. Drugs for the treatment of psychiatric disorders. Hardman JG, Limbird LE The Pharmacological Basis of Therapeutics New York; McGraw-Hill 1996: 399-459
• 31 Hoffmann R, Hendrickse W, Rush A J. et al . Slow-wave activity during non-REM sleep in men with schizophrenia and major depressive disorders.  Psychiatry Res. 2000;  95 215-225
• 32 Hudson J l, Lipinski J F, Keck P E. et al . Polysomnographic characteristics of schizophrenia in comparison with mania and depression.  Biol Psychiatry. 1993;  34 191-193
• 33 Kempenaers C, Kerkhofs M, Linkowski P. et al . Sleep EEG variables in young schizophrenic and depressive patients.  Biol Psychiatry. 1988;  24 (7) 828-833
• 34 Keshavan M S, Reynolds C F, Miewald J. et al . Delta sleep deficits in schizophrenia.  Arch Gen Psychiatry. 1998;  55 443-448
• 35 Salin-Pascual R J, 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;  56 (3) 345-350
• 36 Tekell J L, Hoffmann R, Hendrickse W. et al . High frequency EEG activity during sleep: characteristics in schizophrenia and depression.  Clin EEG Neurosci. 2005;  36 (1) 25-35
• 37 Zarcone V P, Benson K L, Berger P A. Abnormal rapid eye movement latencies in schizophrenia.  Arch Gen Psychiatry. 1987;  44 4548
• 38 Luby E D, Caldwell D F. Sleep deprivation and EEG slow wave activity in chronic schizophrenia.  Arch Gen Psychiatry. 1967;  17 (3) 361-364
• 39 Dijk D J, Brunner D P, Borbély A A. Time course of EEG power density during long sleep in humans.  Am J Physiol. 1990;  258 R650-R661
• 40 Borbély A A, Baumann F, Brandeis D. et al . Sleep deprivation: effect on sleep stages and EEG power density in man.  Electroencephalogr Clin Neurophysiol. 1981;  51 483-493
• 41 Massimini M, Huber R, Ferrarelli F. et al . The sleep slow oscillation as a traveling wave.  J Neurosci. 2004;  24 (31) 6862-6870
• 42 Steriade M, Contreras D, CurroDossi R. et al . The slow (< 1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks.  J Neurosci. 1993;  13 (8) 3284-3299
• 43 Staedt J, Riemann D. Pathophysiologie der Insomnie. Staedt J & Riemann D Diagnostik und Therapie von Schlafstörungen Stuttgart; Kohlhammer Verlag 2007: 25-31
• 44 Hill S, Tononi G. Modeling sleep and wakefulness in the thalamocortical system.  J Neurophysiol. 2005;  93 (3) 1671-1698
• 45 Feinberg I, Thode H C, Chugani H T. et al . Gamma distribution model describes maturational curves for delta wave amplitude, cortical metabolic rate and synaptic density.  J Theor Biol. 1990;  142 (2) 149-161
• 46 Huber M. Felice Ghilardi, Marcello Massimini, Giulio Tononi Local sleep and learning.  Nature. 2004;  430 78-81
• 47 Benington J H, Frank M G. Cellular and molecular connections between sleep and synapticplasticity.  Prog Neurobiol. 2003;  69 71-101
• 48 Hoffman K L, McNaughton B L. Sleep on it: cortical reorganization after-the-fact.  Trends Neurosci. 2001;  25 1-2
• 49 Maquet P. The role of sleep in learning and memory.  Science. 2001;  294 1048-1052
• 50 Steriade M, Timofeev I. Neuronal plasticity in thalamocortical networks during sleep and waking oscillations.  Neuron. 2003;  37 563-576
• 51 Stickgold R, Hobson J A, Fosse R. et al . Sleep, learning, and dreams: off-line memory reprocessing.  Science. 2001;  294 1052-1057
• 52 Walker M P. A refined model of sleep and the time course of memory formation.  Behav Brain Sci. 2005;  28 (1) 51-64
• 53 Peigneux P, Laureys S, Fuchs S. et al . Are spatial memories strengthened in the human hippocampus during slow wave sleep?.  Neuron. 2004;  44 (3) 535-545
• 54 Friston K J. The disconnection hypothesis.  Schizophr Res. 1998;  30 (2) 115-125
• 55 Stephan K E, Baldeweg T, Friston K J. Synaptic plasticity and dysconnection in schizophrenia.  Biol Psychiatry. 2006;  59 (10) 929-939
• 56 Walker M P, Stickgold R. Sleep, Memory and Plasticity.  Annu Rev Psychol. 2006;  57 139-166
• 57 Scheuerecker J, Ufer S, Zipse M. et al . Cerebral changes and cognitive dysfunctions in medication-free schizophrenia – An fMRI study.  J Psychiatr Res. 2008;  42 (6) 469-476
• 58 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;  38 (6) 591-599
• 59 Danos P. Pathology of the thalamus and schizophrenia – an overview.  Fortschr Neurol Psychiatr. 2004;  72 (11) 621-634
• 60 Martin J L, Jeste D V, Caliguri M P. et al . Actigraphic estimates of circadian rhythms and sleep/wake in older schizophrenia patients.  Schizophr. 2001;  47 (1) 77-86
• 61 Wirz-Justice A, Bromundt V, Cajochen C. Circadian disruption and psychiatric disorders: the importance of entrainment.  Sleep Med Clin. 2009;  4 (2) 273-282
• 62 Staedt J, Riemann D. Chronopsychopharmakologie. Staedt J & Riemann D Diagnostik und Therapie von Schlafstörungen Stuttgart; Kohlhammer Verlag 2007: 113-117
• 63 Mai L M, Shieh K R, Pan J T. Circadian changes of serum prolactin levels and tuberoinfundibular dopaminergic neuron activities in ovariectomized rats treated with or without estrogen: the role of the suprachiasmatic nuclei.  Neuroendocrinology. 1994;  60 (5) 520-526
• 64 Takahashi K, Lin J S, Sakai K. Neuronal activity of histaminergic tuberomammillary neurons during wake-sleep states in the mouse.  J Neurosci. 2006;  26 (40) 10292-10298
• 65 Wetter T C, Lauer C J, Gillich G. et al . The electroencephalographic sleep pattern in schizophrenic patients treated with clozapine or classical antipsychotic drugs.  J Psychiatr Res. 1996;  30 (6) 411-419
• 66 Nofzinger E A, Kammen D P, Gilbertson M W. et al . Electroencephalographic sleep in clinically stable schizophrenic patients: two-weeks versus six-weeks neuroleptic-free.  Biol Psychiatry. 1993;  33 (11 – 12) 829-835
• 67 Ayalon van L, Hermesh H, Dagan Y. Case study of circadian rhythm sleep disorder following haloperidol treatment: reversal by risperidone and melatonin.  Chronobiol Int. 2002;  19 (5) 947-959
• 68 Wirz-Justice A, Werth E, Savaskan E. et al . Haloperidol disrupts, clozapine reinstates the circadian rest-activity cycle in a patient with early-onset Alzheimer disease.  Alzheimer Dis Assoc Disord. 2000;  14 (4) 212-215
• 69 Wirz-Justice A, Haug H J, Cajochen C. Disturbed circadian rest-activity cycles in schizophrenia patients: an effect of drugs?.  Schizophr Bull. 2001;  27 (3) 497-502
• 70 Viyoch J, Matsunaga N, Yoshida M. et al . Effect of haloperidol on mPer1 gene expression in mouse suprachiasmatic nuclei.  J Biol Chem. 2005;  280 (8) 6309-6315
• 71 Salín-Pascual R J, Herrera-Estrella M, Galicia-Polo L. et al . Olanzapine acute administration in schizophrenic patients increases delta sleep and sleep efficiency.  Biol Psychiatry. 1999;  46 (1) 141-143
• 72 Sharpley A L, Vassallo C M, Cowen P J. Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT(2C) receptors in vivo.  Biol Psychiatry. 2000;  47 (5) 468-470
• 73 Sharpley A L, Vassallo C M, Pooley E C. et al . Allelic variation in the 5-HT2C receptor (HT2RC) and the increase in slow wave sleep produced by olanzapine.  Psychopharmacology. 2001;  153 (2) 271-272
• 74 Hinze-Selch D, Mullington J, Orth A. et al . Effects of clozapine on sleep: a longitudinal study.  Biol Psychiatry. 1997;  42 (4) 260-266
• 75 Haffmans J, Oolders H, Hoencamp E. et al . Sleep quality in schizophrenia and the effects of atypical antipsychotic medication.  Acta Neuropsychiatrica. 2004;  16 (6) 281-289
• 76 Yamashita H, Morinobu S, Yamawaki S. et al . Effect of risperidone on sleep in schizophrenia: a comparison with haloperidol.  Psychiatry Res. 2002;  109 (2) 137-142
• 77 Seeburg D P, Liu X, Chen C. Frequency-dependent modulation of retinogeniculate transmission by serotonin.  J Neurosci. 2004;  24 (48) 10950-10962
• 78 Smith B N, Sollars P J, Dudek F E. et al . Serotonergic modulation of retinal input to the mouse suprachiasmatic nucleus mediated by 5-HT1B and 5-HT7 receptors.  J Biol Rhythms. 2001;  16 (1) 25-38
• 79 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;  22 (5) 299-308
• 80 Idzikowski C, Mills F J, Glennard R. 5-Hydroxytryptamine-2 antagonist increases human slow wave sleep.  Brain Res. 1986;  378 (1) 164-168
• 81 Idzikowski C, Cowen P J, Nutt D. et al . The effects of chronic ritanserin treatment on sleep and the neuroendocrine response to L-tryptophan.  Psychopharmacology. 1987;  93 (4) 416-420
• 82 Cohrs S, Rodenbeck A, Guan Z. et al . Sleep-promoting properties of quetiapine in healthy subjects.  Psychopharmacology. 2004;  174 (3) 421-429
• 83 Staedt J, Riemann D. Insomnie bei Restless-legs-Syndrom (RLS) und periodischen Beinbewegungen im Schlaf (PLMS). Staedt J & Riemann D Diagnostik und Therapie von Schlafstörungen Stuttgart; Kohlhammer Verlag 2007: 34-42
• 84 Duggal H S, Mendhekar D N. Clozapine-associated restless legs syndrome.  J Clin Psychopharmacol. 2007;  27 (1) 89-90
• 85 Kraus T, Schuld A, Pollmacher T. Periodic leg movements in sleep and restless legs syndrome probably caused by olanzapine.  J Clin Psychopharmacol. 1999;  19 (5) 478-479
• 86 Pinninti N R, Mago R, Townsend J. et al . Periodic restless legs syndrome associated with quetiapine use: a case report.  J Clin Psychopharmacol. 2005;  25 (6) 617-618
• 87 Wetter T C, Brunner J, Bronisch T. Restless legs syndrome probably induced by risperidone treatment.  Pharmacopsychiatry. 2002;  35 (3) 109-111
• 88 Neeper S A, Benson K L, Faull K F. et al . Periodic leg movements in schizophrenia: Incidence and correlates.  Sleep Res. 1992;  21 154
• 89 Diehl A, Braus D F, Büchel C. et al . Tardive dyskinesia: pergolid, a possible therapeutic option.  Psychiatr Prax. 2003;  30 (6) 333-337
• 90 Jaskiw G E, Popli A P. A meta-analysis of the response to chronic L-dopa in patients with schizophrenia: therapeutic and heuristic implications.  Psychopharmacol. 2004;  171 (4) 365-374
• 91 Pajonk F G, Berner D, Kaizl I. et al . The effects of physical exercise on brain morphology in patients with schizophrenia.  Schiz Res. 2008;  98 (Suppl 1) 129-130
• 92 McCurry S M, Gibbons L E, Logsdon R G. et al . Nighttime insomnia treatment and education for Alzheimer’s disease: a randomized, controlled trial.  J Am Geriatr Soc. 2005;  53 (5) 793-802
• 93 Staedt J, Riemann D. Allgemeine Psychotherapie von Schlafstörungen. Staedt J & Riemann D Diagnostik und Therapie von Schlafstörungen Stuttgart; Kohlhammer Verlag 2007: 127-162
• 94 Morin C M, Culbert J P, Schwartz S M. Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy.  Am J Psychiatry. 1994;  151 (8) 1172-1180
• 95 Murtagh D R, Greenwood K M. Identifying effective psychological treatments for insomnia: a meta-analysis.  J Consult Clin Psychol. 1995;  63 (1) 79-89
• 96 Smith M T, Perlis M L, Park A. et al . Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia.  Am J Psychiatry. 2002;  159 (1) 5-11
• 97 Jacobs G D, Pace-Schott E F, Stickgold R. et al . Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison.  Arch Intern Med. 2004;  164 (17) 1888-1896
• 98 Bäuml J, Pitschel-Walz G. Psychoedukation bei schizophrenen Erkrankungen. Stuttgart; Schattauer Verlag 2003
• 99 Zhang L, Samet J, Caffo B. et al . Power spectral analysis of EEG activity during sleep in cigarette smokers.  Chest. 2008;  133 (2) 427-432
• 100 Staedt J, Pless-Steinkamp C, Herfeld F. et al . Einfluss erhöhter Lichtintensität auf die Verweildauer von stationär behandelten depressiven Patienten.  Nervenheilkunde. 2009;  28 (4) 223-226
• 101 Bootzin R R, Nicassio P M. Behavioral treatments for insomnia.  Progress in Behavior Modification. 1978;  6 1-41
• 102 Anderson M W, Zendell S M, Rosa D P. et al . Comparison of sleep restriction therapy and stimulus control in older insomniacs: an update.  Sleep Res. 1988;  17 144
• 103 Brooks J O, Friedman L, Bliwise D L. et al . Use of wrist actigraph to study insomnia in older adults.  Sleep. 1993;  16 151-155
• 104 Cervana K, Dauvilliers Y, Espa F. et al . Effect of cognitive behavioral therapy for insomnia on sleep architecture and sleep EEG power spectra in psychophysiological insomnia.  J Sleep Res. 2004;  13 385-393
• 105 Edinger J, Hoelscher T, Marsh G. et al . A cognitive-behavioral therapy for sleep-maintenance insomnia in older adults.  Psychology and Aging. 1992;  7 282-289
• 106 Friedman L, Bilswise D L, Yesavage J A. et al . A preliminary study comparing sleep resstriction treatments for insomnia in older adults.  J Gerontology. 1991;  46 1-8
• 107 Hoelscher T J, Edinger J D. Treatment of sleep-maintenance insomnia in older adults: sleep period reduction, sleep education, and modified stimulus control.  Psychology and Aging. 1988;  3 258-263
• 108 Morin C M, Kowatch R A, Wade J B. Behavioral management of sleep disturbances secondary to chronic pain.  J Behav Ther Exp Psychiat. 1989;  20 295-302
• 109 Morin C M, Kowatch R A, Barry T. et al . Cognitive-behavior therapy for late-life insomnia.  J Consulting and Clinical Psychology. 1993;  61 137-146
• 110 Rubinstein M L, Rothenberg S A, Maheswaran S. et al . Modified sleep restriction therapy in middle-aged and elderly chronic insomniacs.  Sleep Res. 1990;  19 276
• 111 Spielman A J, Saskin P, Thorpy M J. Treatment of chronic insomnia by restriction of time in bed.  Sleep. 1987;  10 (1) 45-56
• 112 Bernstein D A, Borkovec T D. Progressive Relaxation Training: A Manual for Helping Professions. Champaign, IL; Research Press 1973
• 113 Öst L G. Applied relaxation: description of a coping technique and review of controlled studies.  Behav Res Ther. 1987;  25 (5) 397-409