Glutamatergic medications were associated with a mean Yale-Brown Obsessive Compulsive Scale score reduction of 4.17 for obsessive-compulsive disorder symptoms, according to a recent systematic review and meta-analysis published in JAMA Network Open. The level of evidence was rated as moderate for obsessive-compulsive disorder-specific outcomes and low for overall obsessive-compulsive and related disorder improvement, as noted in the study.
The analysis evaluated 27 double-blind, placebo-controlled randomized clinical trials (RCTs) encompassing 1,369 participants (mean age, 31.5 years; standard deviation, 7.8; 65.6% female). Across the studies, glutamatergic medications demonstrated a large effect size for obsessive-compulsive and related disorder (OCRD) symptom improvement. In obsessive-compulsive disorder (OCD)-specific trials (n=23), the mean Y-BOCS score reduction was -4.17.
Subgroup analyses explored variations by disorder type, augmentation strategy with selective serotonin reuptake inhibitors, and patient refractoriness but found no significant differences. Sensitivity analyses, including a leave-one-out approach, confirmed the stability of the findings. However, high heterogeneity (I² = 88%) and indications of publication bias necessitate further investigation.
Adverse effects were primarily mild and associated with N-acetylcysteine, including nausea, diarrhea, and abdominal discomfort. Limitations of the study included small sample sizes, underrepresentation of certain OCRD subtypes (e.g., skin-picking disorder, trichotillomania), and exclusion of non-English studies. Additionally, the study could not assess dose-dependent effects due to inconsistent reporting across trials.
The findings highlight the potential of glutamatergic medications as therapeutic options for OCRDs, particularly OCD. However, further research is needed to evaluate dose-response relationships and expand the evidence base for broader OCRD subtypes.
Full disclosures and additional details can be accessed in the published study.