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L-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study

Caroline Wass34*, Daniel Klamer1, Evangelos Katsarogiannis2, Erik Pålsson1, Lennart Svensson1, Kim Fejgin1, Inga-Britt Bogren2, Jörgen A Engel1 and Birgitta Rembeck2

Author Affiliations

1 Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, PO Box 431, 405 30 Gothenburg, Sweden

2 Psychiatric Clinic/PVV, Sahlgrenska University Hospital, Topasgatan 2, 421 48 V:a Frölunda, Sweden

3 Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, Canada

4 Department of Psychiatry, Division of Addiction Psychiatry, University of Toronto, Toronto, Canada

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BMC Medicine 2011, 9:40  doi:10.1186/1741-7015-9-40

Published: 18 April 2011



Accumulating evidence suggests that the brain's nitric oxide (NO) signalling system may be involved in the pathophysiology of schizophrenia and could thus constitute a novel treatment target. The study was designed to investigate the benefit of L-lysine, an amino acid that interferes with NO production, as an add-on treatment for schizophrenia.


L-lysine, 6 g/day, was administered to 10 patients with schizophrenia as an adjunctive to their conventional antipsychotic medication. The study was designed as a single-blinded, cross-over study where patients were randomly assigned to initial treatment with either L-lysine or placebo and screened at baseline, after four weeks when treatment was crossed over, and after eight weeks.


L-lysine treatment caused a significant increase in blood concentration of L-lysine and was well tolerated. A significant decrease in positive symptom severity, measured by the Positive And Negative Syndrome Scale (PANSS), was detected. A certain decrease in score was also observed during placebo treatment and the effects on PANSS could not unequivocally be assigned to the L-lysine treatment. Furthermore, performance on the Wisconsin Card Sorting Test was significantly improved compared to baseline, an effect probably biased by training. Subjective reports from three of the patients indicated decreased symptom severity and enhanced cognitive functioning.


Four-week L-lysine treatment of 6 g/day caused a significant increase in blood concentration of L-lysine that was well tolerated. Patients showed a significant decrease in positive symptoms as assessed by PANSS in addition to self-reported symptom improvement by three patients. The NO-signalling pathway is an interesting, potentially new treatment target for schizophrenia; however, the effects of L-lysine need further evaluation to decide the amino acid's potentially beneficial effects on symptom severity in schizophrenia.

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