Neurobiology of Depression and Mechanism of Action of Depression Treatments

Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), may alleviate depressive symptoms but also leave residual symptoms. The mechanism of action of SSRIs increases serotonin (5-HT) activity but decreases norepinephrine (NE) and dopamine (DA) activity. By engaging additional targets (eg, NE, DA) along with 5-HT, clinicians may help patients with residual symptoms and treatment-resistant depression. Dual-acting agents and combination strategies can be used to target specific symptoms or block/activate specific receptors for broader therapeutic benefits. Clinicians who understand the mechanism of action of antidepressants can switch or combine agents as needed to help patients achieve complete remission.