L-lysine as an adjunct to risperidone in patients with chronic schizophrenia: A double-blind, placebo-controlled, randomized trial

Abstract

Increasing evidence suggest that the nitric oxide signaling system of the brain may contribute to the pathophysiology of schizophrenia, making this system a target for development of novel therapeutics. The objective of this study was to investigate the efficacy and safety of l-lysine as an adjunctive to risperidone in the treatment of patients with chronic schizophrenia during an 8-week trial. Seventy-two chronic schizophrenia inpatients with a Positive and Negative Syndrome Scale (PANSS) total score of ≥60 participated in a randomized, double-blind, placebo-controlled trial in the active phase of their disease and underwent 8 weeks of treatment with either l-lysine (6 g/day) or placebo as an adjunctive to risperidone. Patients were evaluated using PANSS and its subscales at baseline and weeks 2, 4, 6 and 8. The primary outcome measure was to evaluate the efficacy of l-lysine in improving schizophrenia symptoms. Repeated measures analysis demonstrated significant effect for time × treatment interaction on the PANSS total (P < 0.001), negative (P < 0.001) and general psychopathology (P < 0.001) subscale scores but not the PANSS positive subscale scores (P = 0.61). The frequency of adverse events (AEs) did not differ significantly between the two treatment groups and no serious AE was observed. The present study demonstrated that l-lysine can be a tolerable and efficacious adjunctive therapy for improving negative and general psychopathology symptoms in chronic schizophrenia. However, the safety and efficacy of higher doses of l-lysine and longer treatment periods still remain unknown. Trial registrationIranian registry of clinical trials (www.irct.ir): IRCT201202201556N33.