Nonpharmacological Interventions for MDD and Their Effects on Neuroplasticity


A poster presented at the 2024 ASCP Annual Meeting discusses the results of a systematic literature review.




A poster at the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting discussed the results of a systematic literature review exploring the effects of nonpharmacological interventions on neuroplasticity in the treatment of major depressive disorder (MDD).

According to the review’s investigators, MDD has been linked to impaired neuroplasticity, and traditional antidepressant treatments and cognitive behavioral therapy (CBT) have been shown to enhance neuroplasticity, thereby alleviating symptoms of MDD. However, there is a lack of recent comprehensive reviews focusing specifically on nonpharmacological treatments and their impact on brain plasticity.1

To explore the impact of these treatments, the review analyzed 116 studies published between January 2013 and December 2023 from an initial pool of 1264 records, involving a total of 5369 participants. To be included, studies had to focus on adults with MDD who were being treated with nonpharmacological interventions either approved by the US Food and Drug Administration (FDA) or under investigation for FDA approval. The studies also needed to provide quantifiable data on neuroplasticity changes from baseline to post-intervention. Exclusions were made for studies involving participants with other mental health conditions or those without brain-specific outcomes.1

The results showed that most studies were of medium quality (69%), according to the investigators, with some rated high (22.4%) and a few low (9.5%). Participant ages ranged from 24.1 to 73.0 years, with a mean age of 41.1 years. The majority of participants were female (59.2%), although only 4.3% of studies reported on race or ethnicity.1

Electroconvulsive therapy (ECT)—which research shows is among the most rapid and effective treatments for multiple types of depression2—was the most frequently studied treatment (45.7% of studies), followed by repetitive transcranial magnetic stimulation (28.4%). Other interventions, including CBT, transcutaneous vagus nerve stimulation, transcranial direct current stimulation, magnetic seizure therapy, functional magnetic resonance imaging neurofeedback, and the Emotional Faces Memory Task, were each utilized in fewer than 10% of studies.1

Of the 57 studies with a healthy control group, 43 (75.4%) observed baseline brain differences between patients with MDD and controls. Most of the studies (92.2%) reported significant functional or structural brain changes following nonpharmacological treatments. Furthermore, 70.6% of the studies examining the relationship between brain changes and symptom improvement found that neuroplasticity changes corresponded with better depression outcomes.1

The review also identified several brain regions where neuroplasticity changes were most commonly observed following treatment. These regions included the default mode network, the dorsolateral prefrontal cortex, the amygdala, the insula, the hippocampus, the superior frontal gyrus, the middle frontal gyrus, the angular gyrus, and the anterior cingulate cortex.1

“This systematic literature review shows that nonpharmacological interventions for MDD lead to changes in neuroplasticity, which correspond with improvement in MDD symptoms,” the investigators concluded. “It also highlights gaps in our understanding of the mechanisms of action of nonpharmacological interventions; though ECT was well represented, more research is needed for other therapies.”

The poster was presented by study co-author Chip Meyer, PhD, of Otsuka Pharmaceutical Development & Commercialization Inc.

Are you interested in learning more about the latest research, clinical characteristics, and treatment approaches associated with major depressive disorder? Check out these recent updates and expert discussions in Psychiatric Times®:

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Stay up-to-date on news related to research on promising new interventions and developments in the treatment of a wide variety of psychiatric disorders at

Note: This article was prepared with the assistance of ChatGPT.


1. Vaishnavi S, Leow A, Nguyen V, et al. Changes in neuroplasticity related to nonpharmacological interventions for major depressive disorder: a systematic literature review. American Society of Clinical Psychopharmacology Annual Meeting. Poster presentation. May 30, 2024. Accessed May 30, 2024.

2. Kim J, Widge AS. Neuromodulation approaches to depressive disorders. Psychiatric Times. March 21, 2024. Accessed May 30, 2024.

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