GABA-associated Depression and Insomnia

Pharmacy Times
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Most currently available sleep aids act at the benzodiazepinereceptor site on the gamma-aminobutyricacidA (GABAA) receptor in the central nervous system(CNS). More than 90% of the GABAA receptors in thebrain contain α1,α2, or α3 subunits, also known as omega1, 2, and 3 subunits. The α1-GABAA receptors are implicatedin sedative/hypnotic and ataxic effects. The α2-GABAA receptors mediate anxiolytic and muscle-relaxanteffects; the α3-GABAA receptors also mediate theseeffects in some cases, according to findings reported inthe Proceedings of the National Academy of Sciences ofthe USA, January 2005, and the Journal of Pharmacologyand Experimental Therapeutics, January 2002.

Sleep disorders, especially insomnia, are a frequentsymptom of depression. There is considerable evidencethat the neurotransmitter GABA is implicated in the biochemicalpathophysiology of mood disorders, includinganxiety and depression. Investigators conducted astudy hoping to identify a variant of the α1-GABAA genein patients institutionalized for a severe depressive disorder.Based on their findings, reported in PsychiatricGenetics (Winter 1998), the investigators concludedthat the α1-GABAA receptor probably did not mediateGABA-associated depression.

Although the receptor site for GABA-associateddepression remains to be identified, it may be the α2-GABAA or α3-GABAA subunit. The use of sedating antidepressantsin patients with depression and comorbidinsomnia is not supported by available evidence,according to findings reported in the Journal of ClinicalPsychiatry, 2004. Because newer nonbenzodiazepinesleep aids act selectively at α1-GABAA receptors, a reasonableassumption is that conventional benzodiazepinesleep aids, which interact nonselectively withall 3 GABAA subunits in the CNS, may provide relief forpatients who experience GABA-associated depressioncomplicated by insomnia.

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