Pathophysiology
Clinical meaning
Pharmacotherapy for anxiety disorders targets the neurochemical imbalances underlying pathological anxiety. Serotonergic hypofunction in the raphe nuclei projections to the amygdala and prefrontal cortex reduces inhibitory modulation of fear circuits; SSRIs restore serotonergic tone by blocking the serotonin transporter (SERT), increasing synaptic 5-HT availability. SNRIs additionally enhance noradrenergic signaling by blocking the norepinephrine transporter (NET), providing dual-mechanism benefit particularly for anxiety with comorbid pain or fatigue. Benzodiazepines enhance GABA-A receptor function by binding the allosteric benzodiazepine site, increasing chloride conductance and neuronal inhibition, providing rapid anxiolysis but with tolerance, dependence, and withdrawal seizure risk. Buspirone acts as a partial 5-HT1A agonist at presynaptic autoreceptors in the raphe nuclei, initially reducing serotonin firing but with chronic use desensitizing autoreceptors and increasing net serotonergic transmission โ explaining its 2-4 week onset delay. The prescribing NP must consider pharmacokinetic profiles (CYP2D6 and CYP3A4 metabolism for drug interactions), patient-specific factors, and evidence-based treatment algorithms when selecting and titrating anxiolytic therapy.