Is Insomnia a Perpetuating Factor for Late-Life Depression in the IMPACT Cohort?

LATE-LIFE DEPRESSION AND INSOMNIA ARE SIGNIFICANT PUBLIC HEALTH ISSUES,1 WITH AS MANY AS 42% OF OLDER ADULTS REPORTING TROUBLES associated with sleep.2 A recent review of community and epidemiologic studies conducted exclusively in or including older-age cohorts (total n = 43,070) reported the prevalence of depression to be approximately 9% and that of insomnia to be approximately 17%.3 The estimates were lower in studies with more stringent criteria, approximately 5% and 10% for depression and insomnia, respectively. Longitudinal studies that have evaluated depression and sleep in the elderly have found that insomnia confers an increased risk for depression.4–7 As might be expected, it is not the only significant risk factor. A meta-analysis of studies in older adults found that recent bereavement, with an odds ratio (OR) of 3.3, was the largest risk factor for late-life depression and that sleep disturbance was second (OR 2.6).8 Nonetheless, insomnia has historically been considered a symptom, as opposed to a disorder. When it occurred with psychiatric illness, insomnia was viewed as a natural consequence of mood dysregulation in which sleep-onset insomnia and early-morning insomnia were considered the cardinal symptoms of anxiety and depression. As a symptom, insomnia was often viewed as a secondary phenomenon that would resolve with remission of, or recovery from, the parent disorder. In recent years, this point of view has partially given way to the perspective that insomnia may exist as a primary disorder9,10 and, when it occurs with psychiatric illnesses, it may be viewed as a comorbid condition.9,11 This change in perspective has occurred owing to several considerations. First, to date, one longitudinal study has shown that insomnia symptoms worsen as patients with recurrent major depressive disorder (MDD) approach new-onset episodes of depression,12 suggesting that insomnia may be a prodromal symptom of depression and may trigger or precipitate new episodes. Second, antidepressants can exert their clinical effects without ameliorating the patients' insomnia complaints. e.g., 13–16 For instance, in a fluoxetine trial, disturbed sleep and fatigue were the most common residual symptoms among depression remitters, (present in 44% and 38% of remitters, respectively).15 In a trial of nortriptyline, although depression remitters had significant decreases in mean sleep disturbance scores on the Pittsburgh Sleep Quality Index,17 their mean score remained above the clinical cutoff and higher than that of healthy controls.18 Third, similar findings have been observed in the cognitive behavioral treatment of depression.19,20 For example, in two separate randomized trials comparing cognitive behavioral treatment for depression to antidepressant medication, approximately 50% of those with remitted depression had residual insomnia, and this was evenly distributed between intervention groups.21,22 Fourth, in significant subsets of patients, insomnia becomes chronic, despite successful resolution of the psychiatric illness.23–27 Fifth, Fava et al. recently reported that coadministration of eszopiclone with fluoxetine resulted in greater sleep improvements and antidepressant effects than fluoxetine alone.28 Finally, there are a number of longitudinal studies showing that insomnia confers an increased risk for depression over time frames of between 6 months and 3 years.4–6,12,29–36 There are also studies that show that insomnia can confer risk over periods that extend over decades.7,37,38 In general, patients with persistent insomnia are approximately 3.5 times more likely to develop depression, as compared with subjects without insomnia complaints. Despite a set of findings suggesting that insomnia is more than a symptom of depression, it does not completely rule out the possibility. Another interpretation of the above findings is that cognitive behavioral treatment for depression and a variety of antidepressant medication therapies improve sleep in a large number of patients. It may be impossible to determine whether insomnia is purely a symptom or a marker of depression severity or if it is purely a separate disorder. More realistically, not all depressed individuals have an insomnia complaint, and, for a large percentage of depressed patients with an insomnia complaint, the insomnia does, in fact, resolve. It may be that, for some individuals, insomnia is simply a symptom that does not transition to a persistent comorbid insomnia. For others, insomnia does represent a comorbid condition that may or may not resolve without targeted intervention. One open question, therefore, is whether acutely depressed patients who already demonstrate persistent insomnia are more likely to remain depressed than patients with no insomnia complaints or than patients with only acute or mild insomnia. In the present study, we specifically evaluate the proposition that persistent insomnia may be a perpetuating factor for depression.