Gamma-Aminobutyric acid (GABA) is the brains main inhibitory neurotransmitter. With relevance to Generalised Anxiety Disorder (GAD) GABAergic circuits are found in the amygdala, hippocampus, locus coeruleus, hypothalamus and septum pellucidum (Andolina et al., 2015).
GABAergic neurons inhibit activation of such brain areas after a stressful event. In GAD, reduced GABAA receptors have been observed, preventing a reduction of anxiety symptoms (Maguire, 2014).
Benzodiazepines are effective for treating somatic symptoms of GAD (Lydiard et al., 2010). Benzodiazepines are agonists on GABAA receptor sites aiding activation (Pottie et al., 2018). Importantly, benzodiazepines do not bind to GABA’s active site but bind to GABAA allosteric receptor sites, changing the enzyme’s shape and thus how it functions (Sigal & Buhr, 1997).
Diazepam (benzodiazepine) rapidly binds to GABAA sites providing quick GAD symptom relief, working quicker than SSRIs (Murphy et al., 1989). Yet, upon discontinuation, after extended use, benzodiazepine-withdrawal syndrome is common (Chouinard, 2004). Explained by an increase in severity of GAD symptoms and is perhaps explained by enzyme change at receptor sites. It is what may cause addiction and dependency (Ashton, 2005). Therefore, individuals should taper off benzodiazepines (Pottie et al., 2018).
A meta-analysis suggested benzodiazepines may significantly increase risk of dementia and may be inappropriate for older adults (Penninkilampi & Eslick, 2018; American Geriatrics Society, 2019). Singh & Oosthuizen (2019) suggest benzodiazepines are irrationally prescribed globally by well-meaning physicians. SSRI's may be a better choice and in fact is first-line treatment for GAD.