Brain glutamate level after treatment with N-acetylcysteine in obsessive-compulsive disorder (OCD) patients

[DavidPS]

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This 2025 study suggests that NAC might be a useful addition to a supplement stack.

Brain glutamate level after treatment with N-acetylcysteine in obsessive-compulsive disorder patients: A randomized trial

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are routinely used to treat patients with obsessive–compulsive disorder (OCD); however, 40 – 60% of patients with OCD do not respond to SSRIs. Glutamate dysfunction may play a key role in OCD pathogenesis. N-acetylcysteine (NAC), a glutamate-modulating drug, targets the glutamatergic system. This study aimed to assess whether the addition of NAC reduces the severity of OCD symptoms in patients with SSRI-treated moderateto-severe OCD. A total of 60 patients with OCD were diagnosed according to the DSM-5 criteria, and severity of the symptoms was assessed using the Yale–Brown obsessive–compulsive scale (Y-BOCS). Patients were administered 2,400 mg/day of SSRIs plus placebo (placebo arm) or 2,400 mg/day (NAC arm) of SSRIs plus NAC for 10 weeks. Serum alanine aminotransferase, aspartate aminotransferase, creatinine, and electrocardiogram were monitored to evaluate the safety of NAC. The Y-BOCS score was not significantly different between the two arms at baseline; however, it was significantly different between the two arms after 4 (P = 0.03) and 10 (P = 0.00) weeks. The NAC arm had a reduction of 8.4 (25.51 – 17.15) points compared with 1.42 (25.07 – 23.65) points for the placebo arm from baseline to 10 weeks. NAC was well-tolerated and caused mild gastrointestinal adverse events. Thus, NAC is an effective glutamate-modulating drug as and can be used as an augmentation therapy with standard treatment in patients with moderate-to-severe OCD.