Glutamatergic medications effective in treating obsessive-compulsive disorder: JAMA

A new study published in the Journal of American Medical Association found that obsessive-compulsive disorder (OCD) and other obsessive-compulsive and related disorders (OCRDs) may benefit from the use of glutamatergic drugs.

Numerous neuropsychiatric problems that significantly disrupt everyday functioning are included in OCD and associated disorders. These disorders, which cause a great deal of anxiety and interfere with day-to-day functioning, include trichotillomania (hair pulling), body dysmorphic disorder (BDD), skin-picking disorder (excoriation disorder), OCD, and hoarding disorder.

Approximately 60% of patients may not react satisfactorily to current therapies, despite their frequent effectiveness by highlighting the need for innovative therapeutic techniques. With an emphasis on randomized clinical trials (RCTs), David Coelho and colleagues carried out this study to assess the amelioration of OCRD symptoms linked to glutamatergic drugs as monotherapy or as an addition to selective serotonin reuptake inhibitors.

On October 16, 2024, electronic searches were performed without date constraints in Web of Science, PubMed, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials. Double-blind RCTs comparing glutamatergic medicines with placebo for patients with OCRDs, regardless of age, gender, sex, or refractoriness were extracted. Excluded were abstracts, research procedures, studies conducted in languages other than English, and trials that included psychotherapy augmentation. Random-effects meta-analyses were used to extract and synthesize the data.

Subgroup analysis was carried out according to the population, augmentation approach, risk of bias, refractoriness of OCRD, type of glutamatergic drug, and OCRD type. To do sensitivity analysis, a leave-one-out method was used. The standardized mean difference was used to gauge the improvement in OCRD symptoms (Cohen d). The mean difference (a decrease in Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] scores) was used to gauge the improvement in obsessive-compulsive disorder (OCD) symptoms.

There were a total of 27 RCTs, with 1369 participants (mean [SD] age, 31.5 [7.8] years; 65.6% female). Drugs that are glutamatergic showed a significant improvement in OCRD symptoms. Glutamatergic drugs showed a substantial mean decrease in Y-BOCS scores in the 23 OCD-specific RCTs. Overall, glutamatergic drugs may be useful in treating OCRDs, including OCD, according to this comprehensive review and meta-analysis. However, careful interpretation is required due to considerable variability and possible publication bias.

Reference:

Coelho, D. R. A., Yang, C., Suriaga, A., Manasa, J., Bain, P. A., Vieira, W. F., Papatheodorou, S., & Salvi, J. D. (2025). Glutamatergic Medications for Obsessive-Compulsive and Related Disorders. In JAMA Network Open (Vol. 8, Issue 1, p. e2452963). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2024.52963