The US Food and Drug Administration approved 15 new antidepressants and identified 18 more in Phase 3 development, according to a recent review, published in BMC Psychiatry. 

Researchers conducted a systematic review that evaluated psychiatric medications approved by the FDA from 2009 through early 2025, as well as investigational drugs in Phase 3 clinical trials for depressive disorders. The analysis described mechanisms of action, indications, dosing, efficacy, and adverse effect profiles.

Using the FDA Label Database, investigators identified medications labeled as “Human Prescription Drug” under New Drug Applications including the terms “depression” or “major depressive disorder” within the Indications and Usage section. Only drugs with an active market status between January 1, 2009, and April 1, 2025, were included. Over-the-counter and non-drug interventions were excluded. To identify drugs in development, the researchers reviewed the US Clinical Trials Registry (ClinicalTrials.gov) for studies classified as “Phase III” with the condition “depression” or “major depressive disorder,” excluding suspended, withdrawn, or terminated trials. Both databases were last searched on April 2, 2025, and findings were independently reviewed by 2 reviewers. 

Several approved and pipeline drugs demonstrated mechanisms extending beyond the traditional monoamine hypothesis, such as modulation of glutamatergic NMDA receptors, GABA-A receptors, and kappa-opioid receptors. Others functioned as partial agonists at 5-HT1A receptors or as serotonin-norepinephrine reuptake inhibitors. All newly approved oral antidepressants during this period were designed for once-daily administration.

“It is estimated that at least 30% of individuals with depression exhibit resistance to conventional antidepressant therapies, and as such, there is a pressing need for both the development of novel antidepressants and their subsequent uptake into clinical practice,” noted lead author Waguih William IsHak, MD, FAPA, of the Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, and the Department of Psychiatry, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California, and colleagues.

The researchers reported no competing interests.

Source: BMC Psychiatry