Glutamatergic Medications for Obsessive-Compulsive and Related Disorders: A Systematic Review and Meta-Analysis

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Obsessive-compulsive and related disorders (OCRDs) affect many individuals, with standard treatments failing approximately 60% of patients.
• Novel therapeutic strategies are crucial for managing OCRDs due to inadequate response to current therapies.

Purpose of the Study:

• To assess the efficacy of glutamatergic medications in treating OCRD symptoms.
• Focus on double-blind, placebo-controlled randomized clinical trials (RCTs) as monotherapy or augmentation to SSRIs.

Main Methods:

• Systematic literature search across major databases (PubMed, Embase, PsycINFO, Web of Science, Cochrane).
• Inclusion of double-blind RCTs comparing glutamatergic medications with placebo for OCRDs.
• Data synthesis using random-effects meta-analyses with subgroup and sensitivity analyses.

Main Results:

• Twenty-seven RCTs with 1369 participants were analyzed.
• Glutamatergic medications demonstrated a large effect size in improving OCRD symptoms (Cohen d = -0.80) with low certainty of evidence.
• Significant reduction in obsessive-compulsive disorder (OCD) symptoms was observed (mean difference in Y-BOCS scores = -4.17) with moderate certainty of evidence.

Conclusions:

• Glutamatergic medications may be effective for treating OCRDs, especially OCD.
• High heterogeneity and potential publication bias warrant cautious interpretation of findings.
• Further research with larger sample sizes is recommended to explore dose-response, other OCRD subtypes, and novel glutamatergic agents.