Most currently available sleep aids act at the benzodiazepine receptor site on the gamma-aminobutyric acidA (GABAA) receptor in the central nervous system (CNS). More than 90% of the GABAA receptors in the brain contain α1,α2, or α3 subunits, also known as omega 1, 2, and 3 subunits. The α1-GABAA receptors are implicated in sedative/hypnotic and ataxic effects. The α2-GABAA receptors mediate anxiolytic and muscle-relaxant effects; the α3-GABAA receptors also mediate these effects in some cases, according to findings reported in the Proceedings of the National Academy of Sciences of the USA, January 2005, and the Journal of Pharmacology and Experimental Therapeutics, January 2002.
Sleep disorders, especially insomnia, are a frequent symptom of depression. There is considerable evidence that the neurotransmitter GABA is implicated in the biochemical pathophysiology of mood disorders, including anxiety and depression. Investigators conducted a study hoping to identify a variant of the α1-GABAA gene in patients institutionalized for a severe depressive disorder. Based on their findings, reported in Psychiatric Genetics (Winter 1998), the investigators concluded that the α1-GABAA receptor probably did not mediate GABA-associated depression.
Although the receptor site for GABA-associated depression remains to be identified, it may be the α2-GABAA or α3-GABAA subunit. The use of sedating antidepressants in patients with depression and comorbid insomnia is not supported by available evidence, according to findings reported in the Journal of Clinical Psychiatry, 2004. Because newer nonbenzodiazepine sleep aids act selectively at α1-GABAA receptors, a reasonable assumption is that conventional benzodiazepine sleep aids, which interact nonselectively with all 3 GABAA subunits in the CNS, may provide relief for patients who experience GABA-associated depression complicated by insomnia.
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