Neural signaling mechanisms in depression: from monoamine hypotheses to emerging rapid-acting antidepressants

This review examines depression neurobiology across classical and contemporary frameworks, discussing how traditional monoaminergic theories guided SSRIs and SNRIs while highlighting their limitations in treatment response and side effects. Recent discoveries of ketamine and psychedelic compounds have revealed alternative mechanisms involving glutamate signaling and synaptic plasticity, prompting re-evaluation of mechanistic models and circuit-level approaches to developing safer, more effective therapies.