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

Abstract: Introduction: People with major depressive disorder (MDD) 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. Methods: 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 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. Results: Of the 1264 records screened, 116 studies with 5369 participants were included. Electroconvulsive therapy (ECT) was the most common treatment (used by 45.7% of the studies), followed by repetitive transcranial magnetic stimulation (28.4%). Of the 57 studies that included a healthy control comparator group, 43 (75.4%) found brain differences at baseline between participants with MDD and the control group. The majority of the studies (107/116; 92.2%) found statistically significant functional or structural changes in the brain following nonpharmacological treatment for MDD. Of the 85 studies that investigated whether there was a relationship between changes in the brain and improvement in MDD symptoms, 60 (70.6%) found that changes in neuroplasticity corresponded with improvement in depression symptoms. Conclusions: This SLR shows that nonpharmacological interventions for MDD lead to changes in neuroplasticity, which correspond with improvement in MDD symptoms.Short Description: This SLR focused on 116 articles with primary results published between January 1, 2013 and December 6, 2023 that included adults with MDD treated with nonpharmacological products. Most studies (92.2%) found statistically significant functional or structural changes in the brain following nonpharmacological treatment for MDD. Of the 85 studies that looked at MDD symptom improvement, 60 found that improvement was correlated with changes in brain neuroplasticity.Name of Sponsoring Organization(s): This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc.