Overview
Clinical Meaning
Selective serotonin reuptake inhibitors (SSRIs) are first line pharmacotherapy for all major anxiety disorders (GAD, panic disorder, social anxiety disorder, OCD, PTSD).
CNPLE
CNPLE
Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy for all major anxiety disorders (GAD, panic disorder, social anxiety disorder, OCD, PTSD). SSRIs selectively block the serotonin transporter (SERT) on presynaptic neurons, preventing reuptake of serotonin (5-HT) from the synaptic cleft. Acutely, this increases synaptic 5-HT levels, but the anxiolytic effect requires 4-6 weeks because of a complex cascade of receptor adaptations. Initially, increased 5-HT activates inhibitory 5-HT1A autoreceptors on raphe nuclei neurons, paradoxically reducing serotonergic firing and potentially worsening anxiety. Over 2-4 weeks, these autoreceptors desensitize (downregulate), allowing restoration of normal firing rates with enhanced net serotonergic transmission. Simultaneously, postsynaptic 5-HT receptors in the amygdala and prefrontal cortex undergo adaptive changes that restore inhibitory modulation of fear circuits. Chronic SSRI treatment also increases brain-derived neurotrophic factor (BDNF) and promotes hippocampal neurogenesis, counteracting stress-induced hippocampal atrophy. Individual SSRIs differ in selectivity for SERT, secondary receptor binding profiles, CYP450 metabolism, half-life, and side effect profiles, guiding NP prescribing decisions.
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