Ramelteon has also shown phase shifting abilities of the circadian rhythm as well as some mixed positive results in jet lag sleep disorder.20,21 Given the previously mentioned beneficial effects of melato-nin on natural sleep regulation, this should be considered a first-line treatment for primary insomnia, especially if the patient is elderly or has issues with rebound insomnia, next day effects, withdrawal, or elements of circadian rhythm sleep disorders. Related melatonin receptor agonists are currently in the later stages of development.
Applications of melatonin in major psychiatric disorders
Sleep disturbance and mood disorders are inexorably linked: 80% of patients with depression report poor-quality sleep, and sleep problems are a criterion for both depression and bipolar disorder.22 A number of studies suggest that sleep problems lead to the development or relapse of mood disorders. Indirect data point toward sleep disturbance as an important etiological factor in the development of depressive disorders.23 Sleep problems also appear to increase the risk of, or can signal subsequent, mood disorder development.24 Clinically, the sleep problem can interact with the mood disorder in many ways—usually as a combination of residual illness symptoms and medication adverse effects—and can lead to misdiagnosis.
Although the theory that disturbances of sleep and mood have a shared pathology is not new, it is beginning to receive more clinical attention. It has been postulated that sleep problems, circadian rhythm disruption, and mood disturbance are either fundamental responses of a shared common mechanism or a mood disorder, and sleep/circadian rhythm dysregulation can occur reciprocally.25 There appears to be a common genetic overlap between circadian rhythm disruption and mood disorders: many of the same features of circadian rhythm sleep disorders can be seen in mood disorders, such as delayed sleep onset and early morning awakening as well as reversal of the normal peaks of energy, mood, and alertness.24,26
Circadian rhythm sleep disorders can present as depressive type symptoms or can be comorbid with the mood disorder. This is especially true in patients with cyclical depression, such as seasonal affective disorder or bipolar spectrum illness.27 Severe circadian rhythm disruption can often be a clinical clue that points toward bipolar rather than unipolar depression.
Changes in the timing and amount of melatonin secretion and excessive sensitivity to the melatonin response to light have been seen in patients with mood disorders.25 Disruption in melatonin secretion in patients with bipolar disorder and depression has also been noted.28 Whether these changes lead to or are a result of the illness is unknown because it is often difficult to separate true biological disruption from the confounding effects of medication and behavior. Many of the antidepressants used to treat mood disorder can also affect the homeostatic drive to sleep as well as disrupt normal chronobiology and sleep architecture.
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