by Justin Jackson , Medical Xpress

Credit: Unsplash/CC0 Public Domain

A systematic review and meta-analysis from the Harvard T.H. Chan School of Public Health reported a large effect of glutamatergic medications on improving symptoms of obsessive-compulsive and related disorders (OCRDs). The study evaluated outcomes across 27 randomized clinical trials, finding significant benefits, particularly for obsessive-compulsive disorder (OCD).

Obsessive-compulsive and related disorders encompass conditions characterized by persistent obsessions or compulsions, affecting approximately 2% to 3% of the U.S. population. People with OCRDs frequently grapple with a variety of disruptions to their daily lives.

Obsessions manifest as intrusive and unwanted thoughts, urges, or images that generate significant anxiety. For instance, some individuals experience intense fears of contamination, leading them to engage in excessive cleaning routines. Others may contend with aggressive or harm-related thoughts despite having no intention of acting on them.

Another prevalent obsession involves the need for symmetry and order. This obsession compels individuals to arrange items in a specific manner and causes them to feel considerable anxiety when this order is disrupted.

Sexual obsessions can also occur, characterized by unwanted and intrusive thoughts about inappropriate or taboo sexual activities. Religious or moral obsessions, often called scrupulosity, involve an excessive concern with religious correctness or moral issues.

Compulsions emerge as repetitive behaviors or mental acts performed to alleviate the anxiety caused by obsessions, further infringing on normal daily functioning. Common compulsions include repetitive hand washing and cleaning to mitigate fears of contamination.

Many individuals constantly check locks, appliances, or other items to prevent perceived dangers or mistakes. Counting rituals, where actions must be performed a specific number of times, are also common methods of reducing anxiety or averting feared outcomes. Organizing and reorganizing objects until they feel “just right” can consume significant time and energy.

These patterns of obsessions and compulsions are just a few of the profound impacts OCRDs have on an individual’s ability to function and maintain a good quality of life.

Standard treatments include selective serotonin reuptake inhibitors (SSRIs), clomipramine, and cognitive behavioral therapy. Despite these options, about 60% of patients, especially those with OCD, do not get full symptom relief, indicating a need for alternative therapeutic strategies.

Emerging research points to glutamatergic dysfunction within cortico-striatal-thalamo-cortical circuits as a potential mechanism contributing to OCRDs, prompting interest in glutamatergic medications as alternative or add-on therapies.

Glutamatergic medications are a class of drugs that target the glutamate neurotransmitter system in the brain. These medications function by modulating glutamate neurotransmission and receptor activity, which can influence synaptic plasticity and neuronal excitability, improving the way brain cells communicate and function.

In the study, “Glutamatergic Medications for Obsessive-Compulsive and Related Disorders: A Systematic Review and Meta-Analysis,” published in JAMA Network Open, researchers synthesized data from 27 trials involving 1,369 participants across five databases.

Inclusion criteria focused on double-blind, placebo-controlled randomized clinical trials assessing glutamatergic medications either as monotherapy or as augmentation to SSRIs in individuals with OCRDs.

Glutamatergic medications demonstrated a substantial overall effect in reducing OCRD symptom severity. While the results show positive outcomes, the researchers still point out a low level of certainty in the evidence due to different trial conditions and potential publication bias of the studies used.

Focusing on OCD specifically, a significant mean reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores was observed (mean difference of −4.17) with a more moderate certainty of evidence.

Subgroup analyses revealed no significant variations across different types of OCRDs, population groups, treatment refractoriness, augmentation strategies, or medication types.

Consistency of results across different clinical trials supports linking glutamatergic medications to better outcomes. The researchers suggest that future studies with larger sample sizes and analyses of dose-dependent effects should be pursued.

More information: David R. A. Coelho et al, Glutamatergic Medications for Obsessive-Compulsive and Related Disorders, JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2024.52963

Journal information:JAMA Network Open

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