Is N-acetylcysteine (NAC) effective for treating Obsessive-Compulsive Disorder (OCD)?

From the Guidelines

N-acetylcysteine (NAC) is not recommended as a primary treatment for Obsessive-Compulsive Disorder (OCD) due to the lack of strong evidence supporting its effectiveness in treating OCD, and instead, first-line treatments such as cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) and selective serotonin reuptake inhibitors (SSRIs) should be prioritized. The most recent and highest quality studies, such as those published in Nature Reviews Disease Primers 1, 2, emphasize the importance of CBT and SSRIs in the treatment of OCD, with CBT having larger effect sizes than pharmacological therapy. While NAC may have some potential benefits in regulating glutamate and reducing oxidative stress, its use as an adjunctive treatment for OCD should be approached with caution and under the guidance of a healthcare provider. Key considerations for treating OCD include:

• Using CBT with ERP as the psychological treatment of choice
• Selecting SSRIs as the first-line pharmacological treatment due to their evidence of efficacy, tolerability, and safety
• Carefully assessing and managing potential adverse effects of SSRIs, such as gastrointestinal symptoms and sexual dysfunction
• Considering the use of intensive CBT protocols for severe or treatment-resistant cases.

From the Research

Efficacy of N-acetylcysteine (NAC) in Treating Obsessive-Compulsive Disorder (OCD)

• The effectiveness of NAC as a treatment for OCD has been investigated in several studies, with mixed results 3, 4, 5, 6, 7.
• A 2016 study found that NAC augmentation therapy may be effective in treating moderate-to-severe OCD, with significant improvements in Y-BOCS total score and obsession subscale compared to placebo 3.
• A 2018 systematic review of clinical evidence found that NAC may be effective in reducing symptoms of OCD, with a mean reduction in Y-BOCS score of -11 points, although the results were not consistently significant across all studies 4.
• However, a 2022 phase III clinical trial found no evidence that NAC reduced symptoms of OCD compared to placebo, with no significant difference in Y-BOCS scores or secondary measures 5.
• A 2024 systematic review and meta-analysis found that NAC augmentation may be beneficial for patients with moderate to severe OCD, with a significant reduction in Y-BOCS scores after 5-8 weeks of treatment, but no significant difference for shorter or longer treatment durations 6.
• Overall, the evidence suggests that NAC may have some potential as an adjunctive treatment for OCD, particularly for patients with moderate to severe symptoms, although further research is needed to fully understand its efficacy and optimal treatment duration 3, 4, 6, 7.

Safety and Tolerability of NAC

• NAC has been found to be well-tolerated and safe in most studies, with mild gastrointestinal adverse events being the most commonly reported side effect 3, 4, 5, 6.
• The safety profile of NAC makes it a potentially useful adjunctive treatment for OCD, particularly for patients who do not respond to or cannot tolerate traditional treatments 4, 7.

Future Research Directions

• Further research is needed to fully understand the efficacy and optimal treatment duration of NAC for OCD, including well-powered studies with sufficient length and consistent treatment protocols 4, 5, 6, 7.
• Additional studies should investigate the potential benefits and limitations of NAC as an adjunctive treatment for OCD, including its effects on symptom reduction, quality of life, and functional outcomes 3, 4, 6, 7.