Multiple factors make insomnia a particular concern for female patients.

Sleep clinicians and researchers are increasingly recognizing that insomnia and comorbid depression are linked conditions, and this has special implications for women who are at a significantly greater risk than men for both disorders. Women with chronic insomnia are at a higher risk for developing or sustaining depression, regardless of their age,1 and since women constitute two thirds of those who suffer from depressive disorders,2 the treatment of depression in women is a substantial health concern. Early relief of insomnia in patients with comorbid depression—whether it is initial, middle, or terminal—is crucial and may increase patient adherence to treatment and improve daytime performance and overall functioning.

Insomnia is an independent risk factor for depression. A recent study reported that people with insomnia were about 10 times more likely than those without insomnia to have clinically significant depression and anxiety.3 In addition, according to the National Institute of Mental Health, up to 90% of patients who suffer from depression also reported insomnia.4

Women, who are twice as likely to suffer from major depressive disorders as men (21.3% vs 12.7%), are also much more likely than men to suffer from insomnia.5 Mayo Clinic HealthSource reports that women’s sleep difficulties can be attributed to fluctuating hormone levels due to monthly menstrual cycles, use of birth control pills, pregnancy, and perimenopause—the 5 to 10 years before and up to 1 year after menstrual periods end.6

Physical and Psychological Causes
Depression and anxiety are two of the most common causes of insomnia.1 Women are more susceptible to stress-induced depression than men, and psychosocial factors may also pose challenges to them. For example, young women often must cope with establishing their careers in a frequently male-dominated workplace while also trying to fulfill their roles as mothers and wives. In efforts to excel in every aspect of the various roles they play, a chronic lack of sleep typically develops that can lead to fatigue and other effects of insufficient sleep. Studies have shown that about 30% of working women report having problems with their sleep, with the problems being more common in women older than 40.6

As women age, physical and hormonal changes take place that make sleep lighter and less sound. Risk of both depression and insomnia appears linked to fluctuations in gonadal hormones during various phases of women’s lives, with the greatest risk of depression taking place during the period between menarche and menopause.7 Women may experience onset or worsening of depressive symptoms during the premenstrual period, as well as during pregnancy or the postpartum period. Other reproductive events such as infertility, miscarriage, or the use of oral contraceptives and hormone replacement therapy have also been shown to cause depression in women.5 Moreover, older women get less deep sleep and are more likely to have frequent awakenings and interrupted sleep. In depressed individuals, sleep disturbances generally cause early morning awakenings, which create difficulty returning to sleep, and this may coexist with difficulty falling asleep and frequent nighttime awakening. For this reason, insomnia treatment should address both sleep onset and sleep maintenance issues.

According to a study at the University of Rochester, depressed patients with insomnia were nearly 11 times more likely to still be depressed at 6 months than those sleeping well, and 17 times more likely to remain ill after a year.3 Hence, it is of utmost importance, regardless of how severe the depression is, that there is relief from the sleep disturbance. This can be particularly challenging considering that most patients are quite concerned about the risk of dependence on any medications they have to take to improve sleep.

Treatment Options
In light of the high risk of relapse and high likelihood of comorbidity, it is crucial to effectively treat both insomnia and depression in women. Thoughtful management approaches must consider known relationships between menstrual or menopausal status and various sleep disorders, and should rely on either pharmacologic or nonpharmacologic treatments, or a combination, to achieve successful relief from insomnia. It is not recommended to use antidepressants off-label for the treatment of insomnia in the absence of depressive disorders. In contrast, the safety and efficacy of the newer benzodiazepine receptor agonist drug class for insomnia are supported by existing clinical experience.8 The US Food and Drug Administration (FDA) guidelines limiting the use of hypnotics predate the newer generation benzodiazepine receptor agonists, and, as such, the guidelines may no longer be truly appropriate for these newer agents.8 In fact, a panel of independent physicians, assembled by the National Institutes of Health (NIH), issued a statement from last year’s state-of-the-science conference on the “Manifestations and Management of Chronic Insomnia in Adults” that said evidence supports the efficacy of cognitive-behavioral therapy and benzodiazepine receptor agonists in the treatment of this disorder, at least in the short term.

Diagnosing and Prescribing
Getting enough sleep has an enormous impact on a woman’s life as it improves not only concentration and social interaction but also performance and general sense of well-being. If a patient experiences sleep disturbances, it must first be clinically established whether the sleep disturbance is a manifestation of another condition such as sleep apnea or any of the psychiatric symptoms mentioned above. It is important to emphasize the various ways in which one can improve one’s sleep before resorting to any pharmacologic treatment. After establishing a diagnosis of a primary sleep disorder, the patient must be educated regarding sleep hygiene issues, which few of our patients practice regularly.

It is also necessary to stress the role that alcohol plays in disrupting sleep, especially since the majority of patients will not volunteer this information unless they are asked specifically, and even when queried, some will still minimize their alcohol consumption. The use of various medications, including over-the-counter medications like decongestants, which patients may not consider contributing factors, has to be addressed as well. Cognitive behavioral therapy has been shown to be beneficial in the treatment of insomnia. If sleep difficulties persist after the above measures have been implemented, it is then beneficial to afford relief through pharmacologic treatments. The nonbenzodiazepine receptor agonists are useful first-line agents due to their safety and efficacy. Most female patients are very concerned about becoming addicted to “sleeping pills.” The NIH supports the use of cognitive behavior therapy and one prescription sleep aid, eszopiclone, which showed that it did not create tolerance in a 6-month study on 500 patients.9

If, during the course of evaluation, it is determined that the insomnia is one of the symptoms of mood disorders, such as major depressive disorder, bipolar disorder, or anxiety disorders, it is then necessary to treat the underlying condition with antidepressants, which include the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). The goals of treatment of depression are to alleviate the neurovegetative symptoms of depression, such as sleep and energy disturbance, to prevent complications, such as suicide (which occur in about 17% of depressed patients), and to restore patients to full or previous-level functioning.

When women complain of fatigue and lack of energy that impair their day-to-day functioning, it can often be attributed to inadequate or lack of restorative sleep. In some cases, the use of antidepressants alone may be sufficient to alleviate all of the symptoms of depression, but in the majority of instances, despite the improvement of mood, women return still complaining of tiredness and continued sleep disturbance. In this setting, it is not unusual to start patients on the benzodiazepine receptor agonists. Not only do patients report relief from sleep disturbance and increased energy levels, but there is also an improvement in overall performance. Patient compliance has also been seen to increase. Results from a recent clinical trial found that the combination of eszopiclone and fluoxetine resulted in significant reductions in clinician-evaluated overall HAM-D17 (Hamilton Depression Rating Scale), the standard scale used by clinicians to assess depression, compared to those taking fluoxetine and a placebo.10

Importantly, whether depression and insomnia occur in tandem or by themselves, when undiagnosed, untreated, treated incorrectly, or treated inadequately, both can worsen. Health care professionals should take this into consideration and discuss any symptoms of a sleep problem, or any psychiatric symptoms, with their patients so that the patients may be diagnosed and treated before these disorders further impact health or quality of life.

Mary Ann Ty, MD, is board certified by the American Board of Psychiatry and Neurology. She practices medicine in Houston.

References
1. National Sleep Foundation. 2002 Sleep in America Poll. Washington, DC: National Sleep Foundation; 2002.

2. Altshuler LL, Cohen LS, Moline ML, et al. The Expert Consensus Guideline Series: Treatment of Depression in Women. Online publication: The McGraw-Hill Companies Inc. March 2001. Available at: www.psychguides.com/ecgs6.php Accessed April 3, 2006.

3. Taylor DJ, Lichstein KL, Durrence HH, et al. Epidemiology of insomnia, depression, and anxiety. Sleep. 2005;28: 1457-1464.

4. National Institute of Mental Health. Depression: What Every Woman Should Know. Bethesda, Md: National Institutes of Health; 2005. Publication 05-4779.

5. Noble RE. Depression in women. Metabolism. 2005;54(5 suppl 1):49-52.

6. Consumer health tips and products: tips for women (and men) in search of a good night’s sleep. Mayo Clinic Web site. Available at: [removed]www.mayoclinic.org/news2006-mchi/3228.html[/removed] Accessed January 25, 2006.

7. Krystal AD. Depression and insomnia in women. Clinical Cornerstone. 2004;6:S19-28.

8. Roth T. Use of low-dose sedating antidepressants vs benzodiazepine receptor agonist hypnotics in treating insomnia. Medscape Today. Available at: www.medscape.com/viewarticle/508820?rss Accessed April 14, 2006.

9. Krystal AD, Walsh JK, Laska E, et al. Sustained efficacy of eszopiclone over six months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep. 2003;26:793-99.

10. Morawetz D. Insomnia and depression: which comes first? Sleep Research Online. 2003;5(2):77-81.