New Research on Insomnia
Sleep Disorders May Precede or Exacerbate Psychiatric Conditions
By Wallace B. Mendelson, MD |
June 1, 2008
Dr Mendelson was professor of psychiatry and clinical pharmacology at the University of Chicago, where he was also director of the Sleep Research Laboratory. He is now a consultant in psychopharmacology in Galveston, Tex. He is a past president of the Sleep Research Society and the recipient of the William C. Dement Academic Achievement Award from the American Academy of Sleep Medicine. At different times in his career he has been Chief of the Section on Sleep Studies at the NIMH Intramural Program and director of the sleep disorder centers at the State University of New York at Stony Brook and the Cleveland Clinic Foundation. He is the author or coauthor of approximately 190 peer-reviewed articles and 3 books on various aspects of sleep research.
Interaction with coexisting illness
Findings from several recent studies indicate that treatment of insomnia can ameliorate the symptoms of some coexisting illnesses. These studies are not fully consistent and can be difficult to interpret because of variations in methodology, duration of treatment, and choice of drug. (The interested reader may wish to look at more detailed reviews.24,25) In a study of 545 patients with depression, Fava and colleagues26 compared fluoxetine(Drug information on fluoxetine) and eszopiclone 3 mg daily with fluoxetine and placebo. Significant improvement was seen at weeks 4 (P = .01) and 8 (P = .002) in the group treated with fluoxetine and eszopiclone on the Hamilton Rating Scale for Depression (HAM-D), and in weeks 2 through 8 on the Clinical Global Impression Severity scale, compared with those who received only fluoxetine and placebo. There were significantly (P = .009) more responders in the combination therapy group than in the monotherapy group (59% vs 48%). This suggests that adjunctive treatment of the accompanying sleep disturbance may result in more effective antidepressant response.
On the other hand, a smaller (N = 190), shorter duration (4-week) study with a different hypnotic (zolpidem 10 mg) and antidepressant (any of 3 SSRIs) found improvements in sleep, alertness, and the SF-36 Vitality subscale but not in the HAM-D.27
It is also possible that benefits for depression that result from adjunctive treatment of coexisting insomnia might not be confined to pharmacological approaches. Manber and colleagues28 recently reported that cognitive-behavioral therapy for insomnia, when given as adjunctive therapy to depressed patients receiving escitalopram(Drug information on escitalopram), resulted in a higher rate of remission of depression at the end of the 12-week study period.
Pollack and colleagues29 randomly selected 595 patients with generalized anxiety disorder who had a sleep disturbance into groups that received escitalopram 10 mg/d plus eszopiclone 3 mg/d and those who received escitalopram plus placebo for 8 weeks. Scores on the Hamilton Rating Scale for Anxiety were reduced by half or more at week 8 significantly (P < .01) more often in the eszopiclone than in the placebo group (62% vs 49%). Remission of both insomnia and anxiety symptoms occurred significantly (P < .05) more often in the eszopiclone group as well.
Similar types of findings (again, with some inconsistencies) have been found in the adjunctive treatment of sleep disturbance in patients with rheumatoid arthritis.24 There are also data that indicate that in the first 6 months of pharmacological treatment of insomnia, there is a relative decline in general health care costs compared with untreated patients with insomnia.30 A recent review of nonpharmacological and pharmacological treatment for insomnia found that 14 of 20 studies showed improvement in health, function, or quality of life.25
New ways of thinking about insomnia
The studies outlined in this article have led to a number of changes in the way sleep researchers approach insomnia. The growing recognition that insomnia is associated with changes in quality of life and a wide range of daytime impairments has led to interest in including these types of variables, as well as traditional measures of sleep, in treatment efficacy studies. In other words, we need to examine not only how treatments affect sleep but how they affect waking life as well.
The growing evidence that insomnia is a risk factor for a variety of other illnesses, and the finding that the treatment of insomnia may improve the therapy of some coexisting illnesses have also contributed to a change in thinking. This found expression in the 2005 NIH state-of- the-science statement on chronic insomnia.31
One result has been that most sleep researchers now refer to insomnia in the context of another illness as "comorbid insomnia," rather than "secondary insomnia." This is much more than a change in phraseology, because it emphasizes that insomnia is a process that can interact with a coexisting illness and is not merely a consequence of the other disorder. Of course, there are a number of ways in which a risk factor might be associated with a second illness: insomnia, for instance, might be an early manifestation of another condition; alternatively, sleep disturbance might make a person more susceptible to another illness, or both might be consequences of a more fundamental disorder. In a recent article, I outlined these various possibilities, using the interrelationship of insomnia and depression as a model.24
If these studies continue to support the comorbid model, this would suggest a very specific change in the way many of us treat insomnia. For sev- eral decades, most sleep researchers emphasized that when insomnia is found accompanying another illness, the best strategy was to treat the underlying illness (for instance, major depression or arthritis), and the insomnia would then "take care of itself." The new data raise the possibility that adjunctive nonpharmacolog-ical or pharmacological management of the sleep disturbance may make it easier to treat the accompanying illness.
1. Zammit GK, Weiner J, Damato N, et al. Quality of life in people with insomnia. Sleep. 1999;22(suppl 2): S379-S385.
2. Daley ME, Leblanc M, Morin CM. The direct and indirect costs associated with insomnia. Sleep. 2004; 27:A281.
3. Mendelson WB, Donnellan M, Schneider WJ. Sleep disturbance as a predictor of employment duration. Sleep Res. 1995;24:295.
4. Johnson LC, Spinweber CL. Quality of sleep and performance in the navy: a longitudinal study of good and poor sleepers. In: Guilleminault C, Lugaresi E, eds. Sleep/WakeDisorders: Natural History, Epidemiology, and Long-Term Evolution. New York: Raven Press; 1983:13-28.
5. Hatoum HT, Kong SX, Kania CM, et al. Insomnia, health-related quality of life, and healthcare consumption: a study of managed-care organisation enrollees. Pharmacoeconomics. 1998;14:629-637.
6. Brassington GS, King AC, Bliwise DL. Sleep problems as a risk factor for falls in a sample of community-dwelling adults aged 64-99 years. J Am Geriatr Soc. 2000;48:1234-1240.
7. Avidan AY, Fries BE, James ML, et al. Insomnia and hypnotic use, recorded in the minimum data set, as predictors of falls and hip fractures in Michigan nursing homes. J Am Geriatr Soc. 2005;53:955-962.
8. Wang PS, Bohn RL, Glynn RJ, et al. Zolpidem use and hip fractures in older people. J Am Geriatr Soc. 2001;49:1685-1690.
9. Agargun MY, Kara H, Solmaz M. Sleep disturbances and suicidal behavior in patients with major depression. J Clin Psychiatry. 1997;58:249-251.
10. Thase ME, Simons AD, Reynolds CF III. Abnormal electroencephalographic sleep profiles in major depression: association with response to cognitive behavior therapy. Arch Gen Psychiatry. 1996;53:99-108.
11. Monroe LJ. Psychological and physiological differences between good and poor sleepers. J Abnormal Psychol. 1967;72:255-264.
12. Rodenbeck A, Huether G, Ruther E, Hajak G. Interactions between evening and nocturnal cortisol secretion and sleep parameters in patients with severe chronic primary insomnia. Neurosci Lett. 2002;324: 159-163.
13. Vgontzas AN, Bixler EO, Lin HM, et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab. 2001;86:3787-3794.
14. Vgontzas AN, Zoumakis M, Bixler EO, et al. Impaired nighttime sleep in healthy old versus young adults is associated with elevated plasma interleukin-6 and cortisol levels: physiologic and therapeutic implications. J Clin Endocrinol Metab. 2003;88:2087-2095.
15. Bonnet MH, Arand DL. Insomnia, metabolic rate, and sleep restoration. J Intern Med. 2003;254:23-31.
16. Bonnet MH, Arand DL. The consequences of a week of insomnia. Sleep. 1996;19:453-461.
17. Nofzinger EA, Buysse DJ, Germain A, et al. Functional neuroimaging evidence for hyperarousal in insomnia. Am J Psychiatry. 2004;161:2126-2128.
18. Troxler RG, Sprague EA, Albanese RA, et al. The association of elevated plasma cortisol and early atherosclerosis as demonstrated by coronary angiography. Atherosclerosis. 1977;26:151-162.
19. Ohayon M, Roth T. Place of chronic insomnia in the course of depressive and anxiety disorders. J Psychiatr Res. 2003;37:9-15.
20. Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411-418.
21. Neckelmann D, Mykletun A, Dahl AA. Chronic insomnia as a risk factor for developing anxiety and depression. Sleep. 2007;30:873-880.
22. Morphy H, Dunn KM, Lewis M, et al. Epidemiology of insomnia: a longitudinal study in a UK population. Sleep. 2007;30:274-280.
23. 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
24. Mendelson W. Impact of insomnia: wide-reaching burden and a conceptual framework for comorbidity. Int J Sleep Wakefulness. 2008;1:118-123.
25. Krystal AD. Treating the health, quality of life, and functional impairments in insomnia. J Clin Sleep Med. 2007;3:63-72.
26. Fava M, McCall WV, Krystal A, et al. Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry. 2006;59:1052-1060.
27. Asnis GM, Chakraburtty A, DuBoff EA, et al. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J Clin Psychiatry. 1999;60:668-676.
28. Manber R, Edinger JD, Gress JL, et al. Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia. Sleep. 2008;31:489-495.
29. Pollack M, Amato DA, Schaefer K, et al. Effects of eszopiclone/escitalopram co-therapy on the percentage of patients experiencing coincident resolution of both insomnia and anxiety in patients with insomnia coexisting with generalized anxiety disorder. Presented at: the American Psychiatry Association 160th Annual Meeting; May 19-24, 2007; San Diego.
30. Hawkins K, Treglia M, Healey P, et al. An analysis of the health and productivity burden of insomnia and its treatment. ISPOR 12th Annual International Meeting; May 19-23, 2007; Arlington, VA.
31. NIH state of the science conference statement on manifestations and management of chronic insomnia in adults statement. J Clin Sleep Med. 2005;1:412-421.