Mechanisms of SSRI Therapy and Discontinuation.
Current Topics in Behavioral Neurosciences January 1, 2024 Trevor Sharp, Helen M Collins 40 citations
SSRIs remain widely prescribed for depression and anxiety, but their therapeutic action is now understood to involve more than simply raising serotonin levels. The current view is that increased serotonin initiates downstream signaling that triggers neural plasticity—functional and structural changes in the brain. These plasticity changes are thought to help relearn emotional experiences, improving mood. This framework also informs research on fast-acting antidepressants like ketamine and psychedelics. However, direct evidence linking plasticity changes to behavioral effects is lacking, and predictions about broader medical applications remain unfulfilled. The mechanisms behind SSRI discontinuation syndrome are less understood, though evidence of rebound increases in serotonin neuron excitability after stopping treatment offers a starting point for future research, drawing parallels with withdrawal from other psychotropic drugs.