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J Psychiatr Res. 2014 Dec;59:125-31. doi: 10.1016/j.jpsychires.2014.08.016. Epub 2014 Sep 6.

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

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Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Department of Psychiatry, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:


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.


Iranian registry of clinical trials ( IRCT201202201556N33.


Clinical trial; Nitric oxide; PANSS; Schizophrenia; l-lysine

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