Chronic Insomnia: Clinical and Research Challenges – An Agenda

Abstract

Chronic insomnia afflicts up to 10% of the population in Western industrialized countries. It is characterized by delayed sleep onset, problems in maintaining sleep, early morning awakening or the feeling of non-restorative sleep coupled with significant daytime impairments on an emotional, social or professional level. It can occur as a co-morbid condition in any other medical or mental disorder, but also as a primary condition. Within the last decade new diagnostic and differential diagnostic approaches have been suggested that enhance diagnostic precision. Epidemiological data and data relating to the health care and cost situation of chronic insomnia suggest a huge burden for society. Chronic insomnia leads to a clear-cut increased risk for psychopathology (i. e., affective disorders) and probably also for cardiovascular and metabolic dysfunction. The pathophysiology of the condition is still poorly understood and will profit from integrating modern neuroscientific approaches (animal studies, molecular biology, neuroimaging, neurophysiology, etc.). Current treatment strategies are mainly based on cognitive behavioural interventions (CBT-I) and hypnotic treatment with benzodiazepine receptor agonists and sedating antidepressants. Although the effectiveness of these treatments has been clearly demonstrated, a substantial proportion of patients proves to be treatment-resistant or profits only poorly. The question of long-term pharmaceutical treatment of chronic insomnia, at least in Europe, is unresolved and urgently needs answers. Novel rational treatment avenues require clues on causes and mechanisms from integrated neuroscientific approaches. The important issues concerning insomnia treatment in the future especially in Europe will be reviewed and discussed critically.

References

• 1 Strobl P. Die Macht des Schlafes in der griechisch-römischen Welt: eine Untersuchung der mythologischen und physiologischen Aspekte der antiken Standpunkte. Verlag Dr. Kovač, Hamburg; 2002
• 2 Summers-Bremner E. Insomnia – a cultural history. Reaktion Books Ltd., London; 2008
• 3 Worthman CM, Melby M. Toward a comparative developmental ecology of human sleep. In: M.A. Carskadon (Ed.).Adolescent Patterns: Biological Social, and Psychological Influences Cambridge University Press, New York; 2002: 69-117
• 4 Von Economo C. Der Schlaf als Lokalisationsproblem. In: O. Pötzl (Ed.). Der Schalf. Mitteilungen und Stellungnahme zum derzeitigen Stande des Schlafproblems. J. F. Lehmanns Verlag, München; 1929: 38-53
• 5 AASM (American Academy of Sleep Medicine) .International classification of sleep disorders.. 2nd edition (ICSD-2). Westchester, II; 2005
• 6 Edinger JD, Bonnet MH, Bootzin RR. et al . Derivation of research diagnostic criteria for insomnia: Report of an American academy of sleep medicine work group.  Sleep. 2004;  27 1567-1596
• 7 NIH, National Institutes of Health state of the science conference statement . Manifestations and management of chronic insomnia in adults, June 13–15, 2005.  Sleep. 2005;  28 1049-1057
• 8 Benca RM, Obermeyer WH, Thisted RA. et al . Sleep and psychiatric disorders: a meta-analysis.  Arch Gen Psychiat. 1992;  49 651-668
• 9 Hudson JL, Pope HG, Sullivan LE. et al . Good sleep, bad sleep: a meta-analysis of polysomnographic measures in insomnia, depression and narcolepsy.  Biol Psychiat. 1992;  32 958-975
• 10 Reite M, Buysse DJ, Reynolds CF. et al . The use of polysomnography in the evaluation of insomnia.  Sleep. 1995;  18 58-70
• 11 Perlis ML, Gehrman P, Terzano M. et al .Sleep EEG in patients with primary insomnia. In: Buyysse D, Sateia M. Insomnia: diagnosis and treatment; 2010: 50-64
• 12 Mendelson W, Garnett D, Gillin JC. et al . The experience of insomnia and daytime and nighttime functioning.  Psychiat Res. 1984;  12 235-250
• 13 Seidel WF, Ball S, Cohen S. et al . Daytime alertness in relation to mood, performance, and nocturnal sleep in chronic insomniacs and noncomplaining sleepers.  Sleep. 1984;  7 230-238
• 14 Stepanski E, Lamphere J, Badia P. et al . Sleep fragmentation and daytime sleepiness.  Sleep. 1984;  7 18-26
• 15 Sugarman JL, Stern JA, Walsh JK. Daytime alertness in subjective and objective in somnia: some preliminary findings.  Biol Psychiat. 1985;  20 741-750
• 16 Bonnet MH, Arand DL. 24-h metabolic rate in insomniacs and matched normal sleepers.  Sleep. 1995;  18 581-588
• 17 Bonnet MH, Arand DL. The consequences of a week of insomnia II: patients with insomnia.  Sleep. 1998;  21 359-368
• 18 Bonnet MH, Arand DL. Activity, arousal, and the MSLT in patients with insomnia.  Sleep. 2000;  23 1-8
• 19 Freedman RR. EEG power spectra in sleep-onset insomnia.  Electroencephalogr Clin Neurophysiol. 1986;  63 408-413
• 20 Merica H, Blois R, Gaillard JM. Spectral characteristics of sleep EEG in chronic insomnia.  Eur J Neurosci. 1998;  10 1826-1834
• 21 Perlis ML, Kehr EL, Smith MT. et al . Temporal and stagewise distribution of high frequency EEG activity in patients with primary and secondary insomnia and in good sleeper controls.  J Sleep Res. 2001;  10 93-104
• 22 Krystal AD, Edinger JD, Wohlgemuth WK. et al . NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes.  Sleep. 2002;  25 630-640
• 23 Buysse DJ, Germain A, Hall ML. et al . EEG spectral analysis in primary insomnia: NREM period effects and sex differences.  Sleep. 2008;  31 1673-1682
• 24 Devoto A, Violani C, Lucidi F. et al . P300 amplitude in subjects with primary insomnia is modulated by their sleep quality.  J Psychosom Res. 2003;  54 3-10
• 25 Devoto A, Manganelli S, Lucidi F. et al . Quality of sleep and P300 amplitude in primary insomnia: a preliminary study.  Sleep. 2005;  28 859-863
• 26 Sforza E, Haba-Rubio J. Event-related potentials in patients with insomnia and sleep – related breathing disorders: evening-to-morning changes.  Sleep. 2006;  29 805-813
• 27 Bastien C, St-Jean G, Morin C. et al . Chronic psychophysio-logical insomnia: hyperarousal and/or inhibition deficits? An ERPs investigation.  Sleep. 2008;  31 887-898
• 28 Yang CM, Lo HS. ERP evidence of enhanced excitatory and reduced inhibitory processes of auditory stimuli during sleep in patients with primary insomnia.  Sleep. 2007;  30 585-592
• 29 Terzano MG, Mancia D, Salati MR. et al . The cyclic alternating pattern as a physiologic component of normal NREM sleep.  Sleep. 1985;  8 137-145
• 30 Terzano MG, Parrino L, Spaggiari MC. et al . CAP variables ands arousals as sleep electroencephalographic markers for primary insomnia.  Clin Neurophysiol. 2003;  114 1715-1723
• 31 Parrino L, Milioli G, de Paolis F. et al . Paradoxical insomonia: The role of CAP and arousals in sleep misperception.  Sleep Med,. in press
• 32 Nofzinger EA, Buysse DJ, Germain A. et al . Functional neuroimaging evidence for hyperarousal in insomnia.  Am J Psychiat. 2004;  161 2126-2129
• 33 Feige B, Al-Shajlawi A, Nissen C. et al . Does REM sleep contribute to subjective wake time in primary insomnia? A comparison of polysomnographic and subjective sleep in 100 patients.  J Sleep Res. 2008;  17 180-190
• 34 Ohayon M. Epidemiology of insomnia: what we know and what we still need to learn.  Sleep Med Rev. 2002;  6 97-111
• 35 Ohayon M, Reynolds III CF. Epidemiological and clinical relevance of insomnia disgnoses algorithms according to the DSM-IV and the international classification of sleep disorders (ICSD).  Sleep Med. 2009;  10 952-960
• 36 Nakata A, Haratani T, Takahashi M. et al . Job stress, social support, and prevalence of insomnia in a population of Japanese daytime workers.  Social Science & Medicine. 2004;  59 1719-1730
• 37 Léger D, Guilleminault C, Dreyfus JP. et al . Prevalence of insomnia in a survey of 12,778 adults in France.  J Sleep Res. 2000;  9 35-42
• 38 Doi Y, Minowa M, Tango T. Impact and correlates of poor sleep quality in Japanese white-collar employees.  Sleep. 2003;  26 467-471
• 39 Gellis LA, Lichstein KL, Scarinci IC. et al . Socioeconomic status and insomnia.  J Abnorm Psychol. 2005;  114 111-118
• 40 Weyerer S, Dilling H. Prevalence and treatment of insomnia in the community: Results from the Upper Bavarian field study.  Sleep. 1991;  14 392-398
• 41 Léger D, Massuel MA, Metlaine A. SISYPHE Study Group . Professional correlates of insomnia.  Sleep. 2006;  29 171-178
• 42 Daley M, Morin CM, LeBlanc M. et al . The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers.  Sleep. 2009;  32 55-64
• 43 Kripke DF. Chronic hypnotic use: deadly risks, doubtful benefit.  Sleep Med Rev. 2000;  4 5-20
• 44 Léger D, Guilleminault C, Bader G. et al . Medical and socio-professional impact of insomnia.  Sleep. 2002;  25 625-629
• 45 Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia.  Sleep. 1999;  22 371-375
• 46 Walsh JK. Drugs used to treat insomnia in 2002: regulatory-based rather than evidence-based medicine.  Sleep. 2004;  27 1441
• 47 Schwabe U, Paffrath D. Arzneiverordnungs-Report 2006.. Springer; 2006
• 48 Hoffmann F, Scharfetter W, Glaeske G. Use of zolpidem and zopiclone on private prescriptions between 1993 and 2007.  Nervenarzt. 2009;  80 578-583
• 49 Mendelson WB, Roth T, Cassella J. et al . The treatment of chronic insomnia: drug indications, chronic use and abuse liability Summary of a 2001 new clinical drug evaluation unit meeting symposium.  Sleep Med Rev. 2004;  8 7-17
• 50 Hohagen F, Rink K, Käppler C. et al . Prevalence and treatment of insomnia in general practice.  Eur Arch Psy Clin N. 1993;  242 329-336
• 51 Backhaus J, Junghanns K, Mueller-Popkes K. et al . Short-term training increases diagnostic and treatment rate for insomnia in general practice.  Eur Arch Psy Clin N. 2002;  252 99-104
• 52 Van Dongen HP, Maislin G, Mullington JM. et al . The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation.  Sleep. 2003;  26 117-126
• 53 Morin CM, LeBlanc M, Daley M. et al . Epidemiology of insomnia: Prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors.  Sleep Med. 2006;  7 123-130
• 54 Orff H, Drummond SP, Nowakowski S. et al . Discrepancy between subjective symptomatology and objective neuropsychological performance in insomnia.  Sleep. 2007;  30 1205-1211
• 55 Riedl BW, Lichstein KL. Insomnia and daytime functioning.  Sleep Med Rev. 2000;  4 277-298
• 56 Fulda S, Schulz H. Cognitive dysfunctions in sleep disorders.  Sleep Med Rev. 2001;  5 423-445
• 57 Edinger JD, Means M, Carney CE. et al . Psychomotor performance deficits and their relation to prior nights’ sleep among individuals with primary insomnia.  Sleep. 2008;  31 599-607
• 58 Altena A, van der Werf YD, Strijers RL. et al . Sleep loss affects vigilance: effects of chronic insomnia and sleep therapy.  J Sleep Res. 2008;  17 335-343
• 59 Altena E, van der Werf Y, Sanz-Arigita EJ. et al . Prefrontal hypoactivation and recovery in insomnia.  Sleep. 2008;  31 1271-1276
• 60 Stickgold R. Sleep-dependent memory consolidation.  Nature. 2005;  437 1272-1278
• 61 Nissen C, Kloepfer C, Nofzinger EA. et al . Impaired sleep-related memory consolidation in primary insomnia.  Sleep. 2006;  29 1068-1073
• 62 Backhaus J, Junghanns K, Born J. et al . Impaired declarative memory consolidation during sleep in patients with primary insomnia: influence of sleep architecture and nocturnal cortisol release.  Biol Psychiat. 2006;  60 1324-1330
• 63 Riemann D, Voderholzer U. Primary insomnia: a risk factor to develop depression?.  J Affect Disorders. 2003;  76 255-259
• 64 Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention?.  JAMA. 1989;  262 1479-1484
• 65 Vollrath M, Wicki W, Angst J. The Zurich study. VIII. Insomnia: association with depression, anxiety, somatic syndromes, and course of insomnia.  Eur Arch Psy Neurol Sci. 1989;  239 113-124
• 66 Dryman A, Eaton WW. Affective symptoms associated with the onset of major depression in the community: findings from the US National Institute of Mental Health Epidemiologic Catchment Area Program.  Acta Psychiat Scand. 1991;  84 1-5
• 67 Brabbins CJ, Dewey ME, Copeland JRM. et al . Insomnia in the elderly: prevalence, gender differences and relationships with morbidity and mortality.  Int J Geriatr Psych. 1993;  8 473-480
• 68 Livingston G, Blizard B, Mann A. Does sleep disturbance predict depression in elderly people? A study in inner London.  Brit J Gen Pract. 1993;  43 445-448
• 69 Breslau N, Roth T, Rosenthal L. et al . Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults.  Biol Psychiat. 1996;  39 411-418
• 70 Chang PP, Ford DE, Mead LA. et al . Insomnia in young men and subsequent depression.  Am J Epidemiol. 1997;  146 105-114
• 71 Weissman MM, Greenwald S, Niño-Murcia G. et al . The morbidity of insomnia uncomplicated by psychiatric disorders.  Gen Hosp Psychiat. 1997;  19 245-250
• 72 Prince MJ, Harwood RH, Thomas A. et al . A prospective population-based cohort study of the effects of disablement and social milieu on the onset and maintenance of late-life depression. The Gospel Oak Project VII.  Psychol Med. 1998;  28 337-350
• 73 Foley DJ, Monjan A, Simonsick EM. et al . Incidence and remission of insomnia among elderly adults: an epidemiologic study of 6 800 persons over 3 years.  Sleep. 1999;  22 S366-372
• 74 Johnson EO, Chilcoat HD, Breslau N. Trouble sleeping and anxiety/depression in childhood.  Psychiat Res. 2000;  94 93-102
• 75 Mallon L, Broman JE, Hetta J. Relationship between insomnia, depression, and mortality: a 12-year follow-up of older adults in the community.  Int Psychogeriatr. 2000;  12 295-306
• 76 Roberts RE, Shema SJ, Kaplan GA. et al . Sleep complaints and depression in an aging cohort: a prospective perspective.  Am J Psychiat. 2000;  157 81-88
• 77 Roberts RE, Robert CR, Chen IG. Impact of insomnia on future functioning of adolescents.  J Psychosom Res. 2002;  53 561-569
• 78 Hein S, Bonsignore M, Barkow S. et al . Lifetime depressive and somatic symptoms as preclinical markers of late-onset depression.  Eur Arch Psy Clin N. 2003;  253 16-21
• 79 Gregory AM, Caspi A, Eley TC. et al . Prospective longitudinal associations between persistent sleep problems in childhood and anxietiy and depression disorders in adulthood.  J Abnorm Child Psychol. 2005;  33 157-163
• 80 Ong SH, Wickramaratne P, Tang M. et al . Early childhood sleep and eating problems as predictors of adolescent and adult mood and anxiety disorders.  J Affect Disorders. 2006;  96 1-8
• 81 Perlis ML, Smith LJ, Lyness JM. et al . Insomnia as a risk factor for onset of depression in elderly.  Behav Sleep Med. 2006;  4 104-113
• 82 Morphy H, Dunn KM, Lewis M. et al . Epidemiology of insomnia: a longitudinal study in a UK population.  Sleep. 2007;  30 274-280
• 83 Neckelmann D, Mykletun A, Dahl AA. Chronic insomnia as a risk factor for developing anxiety and depression.  Sleep. 2007;  30 873-880
• 84 Buysse DJ, Angst J, Gamma A. et al . Prevalence, course, and comorbidity of insomnia and depression in young adults.  Sleep. 2008;  31 473-480
• 85 Cho HJ, Lavretsky H, Olmstead R. et al . Sleep disturbance and depression recurrence in community-dwelling older adults: a prospective study.  Am J Psychiat. 2008;  165 1543-1550
• 86 Gregory AM, Van der Ende J, Willis TA. et al . Parent-reported sleep problems during development and self-reported anxiety/depression, attention problems, and aggressive behaviour later in life.  Arch Pediatr Adolesc Med. 2008;  162 330-335
• 87 Jansson-Fröjmark M, Lindblom K. A bidirectional relationship between anxiety and depression, and insomnia? A prospective study in the general population.  J Psychosom Res. 2008;  64 443-449
• 88 Roane BM, Taylor DJ. Adolescent insomnia as a risk factor for early adult depression and substance abuse.  Sleep. 2008;  31 1351-1356
• 89 Kim JM, Stewart R, Kim SW. et al . Insomnia, depression, and physical disorders in late life: a 2-year longitudinal community study in Koreans.  Sleep. 2009;  32 1221-1228
• 90 Baglioni C, Spiegelhalder K, Lombardo C. et al . Sleep and emotions: focus on insomnia.  Sleep Med Rev. 2010;  14 227-238
• 91 Wojnar M, Ilgen MA, Wojnar J. et al . Sleep problems and suicidality in the national comorbidity survey replication.  J Psychiatr Res. 2009;  43 526-531
• 92 Riemann D, Berger M, Voderholzer U. Sleep and depression – results from psychobiological studies: an overview.  Biol Psychol. 2001;  57 67-103
• 93 Holsboer F. Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy.  J Affect Disorders. 2001;  62 77-91
• 94 Riemann D, Spiegelhalder K, Feige B. et al . The hyperarousal model of insomnia: a review of the concept and its evidence.  Sleep Med Rev. 2010;  14 19-31
• 95 Schwartz SW, Cornoni-Huntley J, Cole SR. et al . Are sleep complaints an independent risk factor for myocardial infarction?.  Ann Epidemiol. 1998;  8 384-392
• 96 Nilsson PM, Nilsson JA, Hedblad B. et al . Sleep disturbance in association with elevated pulse rate for prediction of mortality – consequences of mental strain?.  J Intern Med. 2001;  250 521-529
• 97 Mallon L, Broman JE, Hetta J. Sleep complaints predict coronary artery disease mortality in males: a 12-year follow-up study of a middle-aged Swedish population.  J Intern Med. 2002;  251 207-216
• 98 Schwartz S, Anderson WM, Cole SR. et al . Insomnia and heart disease: a review of epidemiologic studies.  J Psychosom Res. 1999;  47 313-333
• 99 Kripke DF, Garfinkel L, Wingard DL. et al . Mortality associated with sleep duration and insomnia.  Arch Gen Psychiat. 2002;  59 131-136
• 100 Phillips B, Mannino DM. Does insomnia kill?.  Sleep. 2005;  28 965-971
• 101 Suka M, Yoshida K, Sugimori H. Persistent insomnia is a predictor of hypertension in Japanese male workers.  J Occup Health. 2003;  45 344-350
• 102 Gangwisch JE, Heymsfield SB, Boden-Albala B. et al . Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey.  Hypertension. 2006;  47 833-839
• 103 Phillips B, Mannino DM. Do insomnia complaints cause hypertension or cardiovascular disease?.  J Clin Sleep Med. 2007;  3 489-494
• 104 Phillips B, Buzkova P, Enright P. Insomnia did not predict incident hypertension in older adults in the cardiovascular health study.  Sleep. 2009;  32 65-72
• 105 Vgontzas AN, Liao D, Bixler EO. et al . Insomnia with objective short sleep duration is associated with a high risk for hypertension.  Sleep. 2009;  32 491-497
• 106 Lanfranchi PA, Pennestri MH, Fradette L. et al . Night time blood pressure in normotensive subjects with chronic insomnia: implications for cardiovascular risk.  Sleep. 2009;  32 760-766
• 107 Fox K, Borer JS, Camm AJ. et al . Resting heart rate in cardiovascular disease.  J Am Coll Cardiol. 2007;  50 823-830
• 108 Lahiri MK, Kannankeril PJ, Goldberger JJ. Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications.  J Am Coll Cardiol. 2008;  51 1725-1733
• 109 Haynes SN, Adams A, Franzen M. The effects of presleep stress on sleep-onset insomnia.  J Abnorm Psychol. 1981;  90 601-606
• 110 Bonnet MH, Arand DL. Heart rate variability in insomniacs and matched normal sleepers.  Psychosom Med. 1998;  60 610-615
• 111 Monroe LJ. Psychological and physiological differences between good and poor sleepers.  J Abnorm Psychol. 1967;  72 255-264
• 112 Freedman RR, Sattler HL. Physiological and psychological factors in sleep-onset insomnia.  J Abnorm Psychol. 1982;  91 380-389
• 113 Varkevisser M, Van Dongen HP, Kerkhof GA. Physiologic indexes in chronic insomnia during a constant routine: evidence for general hyperarousal?.  Sleep. 2005;  28 1588-1596
• 114 Jurysta F, Lanquart JP, Sputaels V. et al . The impact of chronic primary insomnia on the heart rate-EEG variability link.  Clin Neurophysiol. 2009;  120 1054-1060
• 115 Fang SC, Huang CJ, Yang TT. et al . Heart rate variability and daytime functioning in insomniacs and normal sleepers: preliminary results.  J Psychosom Res. 2008;  65 23-30
• 116 Patel S, Hu FB. Short sleep duration and weight gain: a systematic review.  Obesity. 2008;  16 643-653
• 117 Chen X, Beydoun MA, Wang Y. Is sleep duration associated with childhood obesity? A systematic review and meta-analysis.  Obesity. 2008;  16 265-274
• 118 Spiegel K, Leproult R, van Cauter E. Impact of sleep debt on metabolic and endocrine function.  Lancet. 1999;  354 1435-1439
• 119 Spiegel K, Tasali E, Leproult R. et al . Effects of poor and short sleep on glucose metabolism and obesity risk.  Nat Rev Endocr. 2009;  5 253-261
• 120 Vgontzas AN, Lin HM, Papaliaga M. et al . Short sleep duration and obesity: the role of emotional stress and sleep disturbances.  Int J Obesity. 2008;  32 801-809
• 121 Nilsson PM, Röst M, Engström G. et al . Incidence of diabetes in middle-aged men is related to sleep disturbances.  Diabetes Care. 2004;  27 2464-2469
• 122 Mallon L, Broman JE, Hetta J. High incidence of diabetes in men with sleep complaints or short sleep duration.  Diabetes Care. 2005;  28 2762-2767
• 123 Hayashino Y, Fukuhara S, Suzukamo Y. et al . Relation between sleep quality and quantity, quality of life, and risk of developing diabetes in healthy workers in Japan: the high risk and population strategy for occupational health promotion.  BMC Public Health. 2007;  7 129-137
• 124 Horvath TL, Gao XB. Input organization and plasticity of hypocretin neurons: possible clues to obesity's association with insomnia.  Cell Metab. 2005;  1 279-286
• 125 Youngstedt SD, Kripke DF. Long sleep and mortality: rationale for sleep restriction.  Sleep Med Rev. 2004;  8 159-174
• 126 Kripke DF, Simons RN, Garfinkel L. et al . Short and long sleep and sleeping pills: is increased mortality associated?.  Arch Gen Psychiat. 1979;  36 103-116
• 127 Tamakoshi A, Yoshiyuki O. Self-reported sleep duration as a predictor of all-cause mortality: results from the JACC Study, Japan.  Sleep. 2004;  27 51-54
• 128 Gallicchio L, Kalesan B. Sleep duration and mortality: a systematic review and meta-analysis.  J Sleep Res. 2009;  18 148-158
• 129 Althuis MD, Fredman L, Langenberg PW. et al . The relationship between insomnia and mortality among community dwelling older women.  JAGS. 1998;  46 1270-1273
• 130 Kripke DF, Klauber MR, Wingard DL. et al . Mortality hazard associated with prescription hypnotics.  Biol Psychiat. 1998;  43 687-693
• 131 Mallon L, Borman JE, Hetta J. Is usage of hypnotics associated with mortality?.  Sleep Med. 2009;  10 279-286
• 132 Perlis ML, Giles DE, Mendelson WB. et al . Psychophy-siological insomnia: the behavioural model and a neurocognitive perspective.  J. Sleep Res. 1997;  6 179-188
• 133 Perlis ML, Pigeon WR, Drummond SP. The neurobiology of insomnia. In: Gilman (Ed.) Neurobiology of Disease Elsevier, Burlington, MA; 2006: 735-744
• 134 Spielman AJL, Caruso I, Glovinsky P. A behaviour perspective on insomnia treatment.  Psychiatr Clin North Am. 1987;  10 541-553
• 135 Espie CA, Broomfield NM, MacMahon K. et al . The attention-intention-effort pathway in the development of psychophysiologic insomnia: a theoretical review.  Sleep Med Rev. 2006;  10 215-245
• 136 Bonnet M, Arand DL. Hyperarousal and insomnia: state of the science.  Sleep Med Rev. 2010;  14 9-15
• 137 Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms.  Nature. 2005;  437 1257-1263
• 138 Lu J, Sherman D, Devor M. et al . A putative flip-flop switch for control of REM sleep.  Nature. 2006;  441 589-594
• 139 Winkelman JW, Buxton OM, Jensen E. et al . Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (¹H-MRS).  Sleep. 2008;  31 1499-1506
• 140 Cano G, Mochizuki T, Saper CB. Neural circuitry of stress-induced insomnia in rats.  J Neurosci. 2008;  28 10167-10184
• 141 Brisbare-Roch C, Dingemanse J, Koberstein R. et al . Promotion of sleep by targeting the orexin system in rats, dogs and humans.  Nature Med. 2007;  13 150-155
• 142 Riemann D, Perlis ML. The treatments of chronic insomnia: a review of benzo-diazepine receptor agonists and psychological and behavioural therapies.  Sleep Med Rev. 2009;  13 205-214
• 143 Ancoli-Israel S, Richardson GS, Mangano RM. et al . Long-term use of sedative hypnotics in older patients with insomnia.  Sleep Med. 2005;  6 107-113
• 144 Krystal AD, Walsh JK, Laska E. et al . Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia.  Sleep. 2003;  26 793-799
• 145 Krystal AD, Erman M, Zammit GK. et al . Long-term efficacy and safety of zolpidem extended-release 12,5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: A 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study.  Sleep. 2008;  31 79-90
• 146 DeMicco M, Wang-Weigand S, Zhang J. et al . Long-term therapeutic effects of ramelteon treatment in adults with chronic insomnia: a one-year study.  Sleep. 2006;  29 A234
• 147 Morin CM, Vallieres A, Guay B. et al . Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia.  JAMA. 2009;  301 2005-2015
• 148 Espie CA, MacMahon KM, Kelly HL. et al . Randomized clinical effectiveness trial of nurse-administered small-group cognitive behavior therapy for persistent insomnia in general practice.  Sleep. 2007;  30 574-584
• 149 Green G. Insomniac. University of California Press, Berkeley, Los Angeles, London; 2008
• 150 Riemann D, Voderholzer U, Spiegelhalder K. et al . Chronic insomnia and MRI-measured hippocampal volumes: a pilot study.  Sleep. 2007;  30 955-958+
• 151 Altena E, Vrenken H, van der Werf YD. et al . Reduced orbitofrontal and parietal gray matter in chronic insomnia: a voxel-based morphometric study.  Biol. Psychiatry. 2010;  67 182-185
• 152 Raymann RJ, van Someren EJ. Diminished capability to recognize the optimal temperature for sleep initiation may contribute to poor sleep in elderly people.  Sleep. 2008;  31 1301-1309
• 153 van Straten A, Cuijpers P. Self-help therapy for insomnia: a meta-analysis.  Sleep Med Rev. 2009;  13 61-71
• 154 Ritterband LM, Thorndike FP, Gonder-Frederick LA. et al . Efficacy of internet-based behavioural intervention for adults with insomnia.  Arch Gen Psychiat. 2009;  66 692-698
• 155 Espie C. “Stepped care”: a health technology solution for delivering cognitive behavioral therapy as a first line insomnia treatement.  Sleep. 2009;  32 1549-1558

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