Glutamatergic Medications Promising in Treating OCD and Related Disorders

Glutamatergic medications may possibly be an effective treatment for obsessive-compulsive and related disorders (OCRDs), particularly in obsessive-compulsive disorder (OCD), according to systematic review and meta-analysis study findings published in the JAMA Network Open.

Researchers assessed glutamatergic medications as monotherapy or as adjuvant therapy to selective serotonin reuptake inhibitors across OCRDs of diverse range.

The researchers conducted a systematic review and meta-analysis searching multiple electronic medical databases from inception through mid-October 2024 for double-blind randomized clinical trials (RCTs) assessing glutamatergic medications with placebo comparator in OCRDs regardless of sex, age, gender, or refractoriness. Trials involving psychotherapy augmentation were excluded. The main outcome of interest was improvement in OCRD symptoms, which were evaluated based on total scores from a variety of validated scales. 

Among the included RCTs, 3 studies had high risk of bias, 7 had some concerns of bias, and 17 had low risk of bias. The studies were primarily conducted in Iran (n=15) and the United States (n=8), and 23 studies included adults only; 4 studies included children and adolescents.

Overall, 27 RCTs (N=1369 participants; mean [SD] age, 31.5 [7.8] years; 65.6% women) were included in the analysis, among which 23 RCTs were OCD-specific. OCRD symptoms were improved with glutamatergic medications with a large effect size (Cohens d, -0.80; 95% CI, -1.13 to -0.47; low certainty of evidence; P<.001; I²=88%) and evidence of publication bias.

In 23 OCD-specific RCTs, researchers found that glutamatergic medications resulted in a significant mean reduction in Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] scores (mean difference, -4.17; 95% CI, -5.82 to -2.52; moderate certainty of evidence; P<.001; I²=88%) with no evidence of publication bias according.

No significant differences in the magnitude of the effect size of glutamatergic medications on OCRD symptoms by population, augmentation strategy, refractoriness of OCRD, type of glutamatergic medication, risk of bias, or type of OCRD were found in subgroup analyses. Additionally in subgroup analyses, no significant mean differences were found by population, augmentation strategy, refractoriness of OCRD, type of glutamatergic medication, or risk of bias.

“These findings indicate that glutamatergic medications may be effective in treating OCRDs, particularly OCD,” the investigators concluded, “However, high heterogeneity and potential publication bias necessitate cautious interpretation.”

Systematic review and meta-analysis limitations include the underpowered sample sizes of the RCTs and the limited number of studies for some subgroups, the exclusion of non-English studies, and no evaluation of dose-dependent effects. In addition, inconsistent reporting was noted across the included studies.

This article originally appeared on Psychiatry Advisor