L-Arginine Add-On Treatment for Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

Abstract

Current drug treatments for schizophrenia are only partially effective and combination/augmentation strategies are commonly used. Nitric Oxide (NO) may play a role in the pathophysiology of schizophrenia. L-arginine is the precursor of NO. In this study, we aimed to investigate whether L-arginine add-on to current medication might improve positive, negative, and depressive symptoms in schizophrenia/ schizoaffective disorder patients in partial remission. The study was designed as a randomized, double-blind, placebo-controlled, crossover study of L-arginine 3 g b.i.d. as an add-on treatment to the patients' usual medication. Twelve patients diagnosed with schizophrenia/schizoaffective disorder were included. The duration of the treatment was 3 weeks, with a wash-out period of 7 days before alternation for the second arm. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Clinical Global Impression (CGI) scales. The study was supported by Hacettepe University Scientific Research and Development Office (Project No: 011D0110101013) (Clinical Trials.gov Identifier: NCT02398279). Our analyses revealed that L-arginine 6 g/day add-on to usual treatment was not superior to placebo for positive, negative, and depressive symptoms associated with schizophrenia as assessed with PANSS, CDSS and CGI scales. In our study, L-arginine did not seem to have an effect on schizophrenia symptoms. Studies with a larger sample size, with higher doses of L-arginine, and with a longer duration are needed for a definite conclusion.