Benzodiazepines modulate the actions of GABA via effects on GABA-A receptors, with their binding site within the ion channel complex, with a mainly synaptic location.3 It has been suggested that generalized anxiety disorder may be associated with impaired benzodiazepine receptor activity.3 Targeting α-2 subunits of the GABA-A receptor may produce anxiolytic effects without sedation, but activation of the α-3 subunits also has anxiolytic effects. Both the α-2 and α-3 GABA-A receptor subtypes are localized to areas including the amygdala and cortical regions, which are known to be related to anxiety.3
In a meta-analysis, the effect size of benzodiazepines in reducing generalized anxiety disorder symptoms was greater than that of either SSRIs or SNRIs.7 In a separate network meta-analysis, benzodiazepines had significant effects on symptoms in patients with social anxiety disorder versus waitlist.9
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