Changes in Neural Activities and Neuroplasticity Related to Nonpharmacological Interventions for Major Depressive Disorder: A Systematic Literature Review

People with major depressive disorder (MDD) can have impaired neuroplasticity. Antidepressant treatment and some nonpharmacological interventions can lead to changes in neuroplasticity that improve MDD symptoms. However, there are no recent systematic literature reviews (SLRs) on the effect of nonpharmacological interventions for MDD on neuroplasticity. Therefore, we conducted an SLR of articles with primary results published between January 1, 2013, and December 6, 2023, that included adults with depression or MDD (MDD used to refer to both) treated with nonpharmacological products that are U.S. Food and Drug Administration (FDA) cleared and indicated for MDD or are investigative and need FDA review and clearance for use outside of clinical trials. From the 1257 records screened, 101 studies with 4746 participants were included. Electroconvulsive therapy was the most common treatment (used by 46.5% of the studies), followed by repetitive transcranial magnetic stimulation (35.6%). Of the 54 studies that included a healthy control comparison group, 42 (77.8%) found brain differences at baseline between the MDD group and the control group. Most of the studies (95 studies; 94.1%) found statistically significant functional or structural changes in the brain following nonpharmacological treatment for MDD. Of the 74 studies that investigated whether there was a relationship between changes in the brain and improvement in MDD symptoms, 53 (71.6%) found that changes in neuroplasticity corresponded with improvement in depression symptoms. This SLR shows that nonpharmacological interventions for MDD lead to changes in neuroplasticity, which correspond with improvement in MDD symptoms.