Clinical Relevance of Disturbances of Sleep and Vigilance in Major Depressive Disorder

Abstract

The primary objective of this article is to provide a concise review of the clinical relevance of sleep and vigilance in major depressive disorder. PubMed was reviewed (1990-2009) and English-language articles were identified using the key words sleep and depression and sleep and antidepressants. Secondary searches included articles cited in sources identified by the primary search. The narrative review provides brief descriptions of the normal physiology of sleep and changes associated with depression, as well as the impact of various treatments on these processes. Although it has long been known that sleep disturbances are an important characteristic of depression, relatively few studies have been conducted with the newer-generation antidepressants. Neither of the most widely used classes of antidepressants, the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, have particularly beneficial effects on sleep and, among the medications that reliably improve sleep efficiency, including mirtazapine and the tricyclic antidepressants, problems with daytime sedation can offset therapeutic benefit. Despite relatively widespread use, trazodone has not been demonstrated to be an effective and safe hypnotic in patients taking other antidepressants. For many patients, ongoing concomitant treatment with benzodiazepines and related drugs is the preferred option, again without convincing empirical support of longer-term efficacy. Among newer and investigational antidepressants, agomelatine shows promise with respect to both overall safety and effects on insomnia, although possible negative effects on liver function warrant further study. Sleep disturbances are a significant aspect of depressive syndromes, and relief of insomnia remains an important unmet need in antidepressant therapeutics. Development of a well-tolerated antidepressant medication that rapidly improves sleep maintenance without daytime sedation is a priority for drug development.