Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

Anxiolytics primarily act by facilitating the effects of GABA and antagonizing ACh-N receptors. They also act on the brain’s dopaminergic pathway (Chen et al., 2018). Pharmacologic agents mostly used to treat Generalized Anxiety Disorder (GAD) include antidepressants, benzodiazepines, and Buspirone. The commonly prescribed antidepressants for GAD are selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

SSRIs stimulate 5-HT1 receptors, with antidepressant and anxiolytic effects; 5-HT2 receptors which cause anxiety, insomnia, and sexual dysfunction; and 5-HT3 receptors that cause nausea and headache. Therefore SSRIs can alleviate and cause anxiety (Garakani et al., 2021). SNRIs have both 5-HT and norepinephrine mechanisms of action. Benzodiazepines act as GABA-A agonists (Edinoff et al., 2021). GABA is the major inhibitory neurotransmitter in the CNS. Buspirone is a 5-HT1A partial agonist whose action is mediated by serotonin receptors. It also has some affinity for dopamine. Buspirone has an efficacy similar to that of benzodiazepines.

SSRIs and SNRIs are the first-line treatment option for GAD. They are used as first-line therapy due to their favorable risk-benefit ratio.  SSRIs and SNRIs are effective in treating GAD, but their effect is seen only after being taken for a few weeks (Garakani et al., 2021). Benzodiazepines in small to moderate doses are usually effective. However, their sustained use can cause physical dependence. One treatment strategy for GAD entails initiating therapy with simultaneous use of a benzodiazepine and an antidepressant. When the antidepressant becomes effective, the benzodiazepine is tapered. Benzodiazepines have a faster onset than other anxiolytics. However, they are not recommended for monotherapy use since they are linked with physiologic and psychologic dependence (Edinoff et al., 2021). Therefore, they are recommended as adjuncts to SSRIs. Furthermore, Buspirone is also effective and can be useful among patients who do not respond to or who cannot tolerate SSRIs and SNRIs (Melaragno, 2021).

References

Chen, X., Broeyer, F., de Kam, M., Baas, J., Cohen, A., & van Gerven, J. (2018). Pharmacodynamic response profiles of anxiolytic and sedative drugs. British journal of clinical pharmacology, 83(5), 1028–1038. https://doi.org/10.1111/bcp.13204

Edinoff, A. N., Nix, C. A., Hollier, J., Sagrera, C. E., Delacroix, B. M., Abubakar, T., Cornett, E. M., Kaye, A. M., & Kaye, A. D. (2021). Benzodiazepines: Uses, Dangers, and Clinical Considerations. Neurology international, 13(4), 594–607. https://doi.org/10.3390/neurolint13040059