Monday, January 6, 2025

Glutamatergic Medications May Reduce Symptoms of Obsessive-Compulsive, Related Disorders

Glutamatergic medications such as N-acetylcysteine (NAC) and memantine may help reduce symptoms of obsessive-compulsive and related disorders (OCRDs), according to a meta-analysis in JAMA Network Open.

David R. A. Coelho, M.D., M.P.H., of Harvard T.H. Chan School of Public Health, and colleagues analyzed data from 27 randomized clinical trials involving 1,369 patients with OCRDs, including 23 studies of patients with obsessive-compulsive disorder, two studies of patients with trichotillomania, and two studies of patients with skin-picking disorder. Ten studies investigated NAC, four explored memantine, three each assessed lamotrigine and riluzole, two examined topiramate, and one study each assessed amantadine, glycine, L-carnosine, minocycline, and pregabalin. Outcomes were improvements in OCRD symptoms. The patients’ symptoms were measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and other standardized assessments.

Overall, 688 patients in the studies were taking glutamatergic medications and 681 were not. Those who took glutamatergic medications had significantly fewer symptoms of their disorders than those in the control group (effect size of 0.8). In the 23 studies that focused on obsessive-compulsive disorder, those who took glutamatergic medications reduced their Y-BOCS scores by an average of 4.17 more points compared with those in the control group.

“Glutamatergic medications can modulate synaptic plasticity and neuronal excitability, potentially alleviating OCRD symptoms,” Coelho and colleagues wrote. “For instance, NAC has been shown to increase glutathione levels and modulate the glutamatergic system, reducing oxidative stress.”

However, the researchers noted several limitations to their meta-analysis, including the relatively small sample sizes of the trials and the limited number of studies for several medications as well as disorders outside of obsessive-compulsive disorder.

“Future research with larger sample sizes should focus on dose dependent effects, additional OCRD subtypes, and novel glutamatergic treatments to enhance our understanding and treatment strategies,” the researchers wrote.

For related information, see the American Journal of Psychiatry article “Harmonizing the Neurobiology and Treatment of Obsessive-Compulsive Disorder.”

(Image: Getty Images/iStock/mapo)




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