Recycling N-acetylcysteine: A review of evidence for adjunctive therapy in schizophrenia.

Introduction: All symptoms in schizophrenia may impact functioning. Although Food and Drug Administration-approved medications typically benefit positive symptoms, negative symptoms are generally refractory to medication interventions. N-acetylcysteine's (NAC) influence on glutamatergic neurotransmission has been established. An emerging body of research has attempted to correlate this action with reduction in symptom severity, evaluating response in positive, negative, and cognitive symptom domains.

Methods: A literature review was performed to analyze available data on NAC intervention and improvement in the positive, negative, and cognitive symptom domains in patients with schizophrenia. Quality of evidence was systematically assessed to determine level of certainty in results.

Results: Three randomized controlled trials were identified. Across studies, negative symptoms decreased more with NAC compared to placebo; ranging between 11.9% and 24.1%. The assessment determined a low level of certainty regarding benefit of NAC on negative and cognitive symptoms and moderate certainty for NAC regarding findings of side effects and lack of benefit on positive symptoms.

Discussion: Consistent reporting of benefit in negative symptoms is found across studies of NAC intervention. These improvements are notable for symptoms that have generally remained refractory to medication intervention. Inconsistent benefit was reported in positive and cognitive symptoms. GRADE (grading of recommendations assessment, development and evaluation) assessment of current evidence indicates a low certainty of benefit for negative symptoms with standard use of NAC in patients with schizophrenia. However, a trial of this low-risk intervention may be warranted in patients with resistant negative symptoms and subsequent impaired functioning despite appropriate antipsychotic therapy as they may experience additional benefit in this symptom domain.