N-Acetyl-Cysteine in a double-blind randomized placebo-controlled trial: Towards biomarker guided treatment in early psychosis
Poster B66, Friday, October 21, 11:30 am - 1:00 pm, Le Baron
Philippe Conus1, Margot Fournier2, Lijing Xin3, Philipp S Baumann1,2, Luis Alameda1,2, Matcheri S Keshavan4, Philippe Golay1, Mehdi Gholam-Rezaee1, Rolf Gruetter5, Michel Cuenod2, Larry J Seidman4, Kim Q Do2; 1Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerlandausanne University, 2Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland, 3Animal imaging and technology core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Switzerland, 4Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, Boston, Massachusetts, USA, 5Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Purpose: Recent evidence points to a critical role of redox dysregulation induced oxidative stress in the pathophysiology of early phases of schizophrenia. An add-on trial with N-Acetyl-Cysteine (NAC) led to a reduction in negative symptoms in chronic schizophrenia patients. Aim of this study was to explore impact of addition of NAC to standard treatment in early psychosis (EP) patients. Methods: Double-blind, randomized, placebo-controlled trial of addition of NAC, 2700 mg daily, to antipsychotic treatment over 6 months. Monthly assessment of PANSS, GAF, SOFAS and antipsychotics treatment; quantification of brain glutathione levels (GSHmPFC) by 1H-magnetic-resonance-spectroscopy and of blood cells glutathione (GSHBC) and glutathione peroxidase activity (GPxBC) as marker of oxidation status at the beginning and end of treatment. Results: 63 patients were included. Spectroscopy data showed that GSHmPFC increased by +23% in the NAC group, while it tended to decrease by -5% in the placebo group (p=0.005). No significant difference between NAC and placebo patients was observed on global changes in negative symptoms, positive symptoms or functional outcome. However, in patients with high-baseline oxidation status ( GPxBC >22.3U/gHb), subgroup explorations revealed an improvement of positive symptoms over time compared to patients with low-baseline GPx (p=0.02). Conclusions: While addition of NAC induced an increase of brain GSH, it had no impact on symptomatic and functional outcome in EP patients. However, in patients with high oxidation status, addition of NAC leads to significantly greater improvement in positive symptoms. Future studies on antioxidant interventions in EP should consider biomarker guided treatment.
Topic Area: Psychopharmacology