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 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, 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

Conclusion

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.
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