Efficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis

Objective. To assess the efficacy and safety of N-acetylcysteine in the treatment of chronic pain. Methods. A systematic search was carried out until April 2020 for clinical studies of N-acetylcysteine in the management of any persistent or recurrent chronic pain condition for adults >= 18 years old. Risk of bias was assessed using the validated risk of bias tools. When appropriate, a meta-analysis using a random-effects model was performed, with a fixed-effect model for sensitivity analysis. Results. Nine studies (n = 863) were included (five randomized controlled trials [RCTs], two open-label non-comparative studies and two comparative studies), that evaluated patients with sickle cell disease (3), complex regional pain syndrome (1), pelvic pain/endometriosis (2), rheumatoid arthritis (1), diabetic neuropathy (1), and chronic neuropathic pain (1). In the pooled analysis of three RCTs, N-acetylcysteine did not reduce pain intensities (SMD -0.21, 95% confidence interval [CI]: -0.33 to 0.75, random-effects), improve functional outcomes (SMD 0.21, 95% CI -0.33 to 0.75) or quality of life (SMD 0.60, 95% CI: -4.44 to 5.64); however, sensitivity analysis with a fixed effect model demonstrated an effect for pain intensities and function. Due to adverse events being inconsistently reported, no conclusion could be made regarding safety of N-acetylcysteine in chronic pain. Conclusions. While there is some evidence to indicate N-acetylcysteine may provide analgesic efficacy for certain pain conditions, there is insufficient evidence to provide definitive evidence on NAC in chronic pain management. Larger-size RCTs spanning a variety of chronic pain conditions are needed to determine N-acetylcysteine's role, if any, in pain medicine.