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

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


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 registration: Iranian registry of clinical trials (www.irct.ir): IRCT201202201556N33.

Keywords: Clinical trial; Nitric oxide; PANSS; Schizophrenia; l-lysine.

Publication types

  • Address
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Chronic Disease
  • Depression / drug therapy
  • Depression / etiology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Lysine / therapeutic use*
  • Male
  • Psychiatric Status Rating Scales
  • Risperidone / therapeutic use*
  • Schizophrenia / complications
  • Schizophrenia / drug therapy*
  • Treatment Outcome
  • Young Adult


  • Antipsychotic Agents
  • Lysine
  • Risperidone

Associated data

  • IRCT/IRCT201202201556N33