“Comorbid” Insomnia

Major depression

Ninety percent of patients report insomnia or daytime sleepiness and it is one of the diagnostic criteria for the disorder.[5,15] Consistent with the traditional model, nonsedating antidepressant treatment of patients who have insomnia co-occurring with depression resolves the sleep difficulty in majority of the cases.[16–18]

Mania

Eighty percent of manic patients experience a decrease in the ability to sleep and a decreased need for sleep.[5,19] Therapies for mania generally tend to be sedating, and sleep generally increases with treatment.[20,21]

Anxiety disorders

Most commonly associated disorders are GAD and PTSD. It is a diagnostic criteria for these disorders, with majority of patients reporting problems in initiating or maintaining sleep.[5,22] There is some evidence that SSRIs improve sleep in GAD[23] while the data on sleep improvement after treatment in PTSD are inconsistent.[12]

Schizophrenia

Sleep disturbances are not a diagnostic criteria for schizophrenia; however, sleep difficulties are common in this group.[24,25] Most primary schizophrenia treatments generally enhance sleep, but there are no data on the effects of treatment on sleep in this population.[12]

The challenge to the traditional symptom model comes from data that suggest a bidirectional relationship between sleep and psychiatric disorders, and the greatest evidence for the failure of the symptom model that has been obtained is related to sleep problems co-occurring with major depression. This evidence suggests that insomnia is not just a symptom and also has independent importance in terms of clinically relevant outcomes and the course of the disorder. Sleep disturbance seems to be associated with an independent increase in the risk of suicidal ideation and completed suicide.[26,27] Insomnia also seems to predict a greater future risk of depression (and anxiety disorders and alcoholism).[28–30] Residual insomnia after the otherwise successful antidepressant therapy is associated with an increased risk of depression relapse.[31]

Data on the treatment of insomnia co-occurring with depression are the strongest blow to the symptom model. Initiating antidepressant treatment with a hypnotic agent in addition to an antidepressant medication leads not only to a greater improvement in sleep but also a faster and more complete antidepressant response.[32,33] A placebo-controlled study of 545 patients identified that the addition of eszopiclone (3 mg) to fluoxetine had a significant therapeutic effect not only on sleep but also on nonsleep features of depression.[32] In addition, treatment of residual insomnia after the otherwise successful SSRI therapy with zolpidem (10 mg) resulted in a significant improvement in sleep and ratings of daytime function.[34] If sleep were merely a symptom, targeting treatment of sleep difficulties with hypnotic therapy would not be expected to improve the antidepressant outcome over the administration of a therapeutic antidepressant regimen.

Despite the emergence of this new bidirectional approach, there are some key issues that need to be addressed. The evidence of hypnotics as cotherapy is limited to a few agents and the efficacy of other insomnia therapies including other medications and nonpharmacological therapies needs to be studied. It also appears that insomnia agents vary in the degree to which they are effective as cotherapies for depression.[33] Also, another unresolved issue is whether benefits depend upon the antidepressant therapy implemented, as the current large-scale placebo-controlled trial was performed only with fluoxetine.[32] Also important to determine is whether or not the same beneficial effects noted with cotherapy with antidepressants and hypnotics can be achieved with single-agent treatment with a sedating antidepressant like mirtazapine or TCA. Also, the timing of initiating insomnia therapy needs to be determined: whether to add insomnia treatment to the initial treatment regimen or wait to see if there is an incomplete response to the initial antidepressant therapy before initiating insomnia therapy. Ideally, the means should be developed to predict before initial therapy who is most likely to benefit from insomnia cotherapy. Also what needs to be established is the duration that cotherapy should continue for. Also, all the studies currently have been performed in patients with major depression; the same needs to be replicated in other psychiatric disorders. One objection to cotherapy may come from those practicing sleep deprivation as a treatment for major depression. The answer may lie in the fact that it is effective only in a subpopulation of cases and one of the side-effects of sleep deprivation therapy is actually worsening of depressive symptoms which actually supports the cotherapy model indirectly.

In patients diagnosed with chronic insomnia, major depression (14% of all cases), dysthymia (9% of all cases), and anxiety disorders (24% of all cases) are commonly comorbid withinsomnia.[35] When patients report disturbances in their sleep, its significance in relation to frequency, duration, and daytime impairment must be assessed, and a psychiatrist must determine whether the sleep disturbance affects mood, motor performance, or cognitive function. Thus it is fair to say that disturbances of sleep and wakefulness can no longer be viewed only as symptoms or markers of psychiatric disease. Data from research support the additional viewpoint that they can be independent contributors to psychiatric phenomena, related to psychiatric illness in a bidirectional fashion. The understanding of these conditions is, therefore, crucial for psychiatrists and the clinical evaluation and treatment of sleep disorders in addition to psychiatric diagnoses should be the professional focus.