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Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress.

Project for Schizophrenia Research, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan. Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Japan. Division of Molecular Medicine and Therapy, Tohoku University Graduate School of Medicine, Sendai, Japan. Graduate School of Education, University of Tokyo, Tokyo, Japan.

Psychiatry and clinical neurosciences. 2018;(1):35-44
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Abstract

AIM: The aim of this clinical trial was to obtain proof of concept for high-dose pyridoxamine as a novel treatment for schizophrenia with enhanced carbonyl stress. METHODS Ten Japanese schizophrenia patients with high plasma pentosidine, which is a representative biomarker of enhanced carbonyl stress, were recruited in a 24-week, open trial in which high-dose pyridoxamine (ranging from 1200 to 2400 mg/day) was administered using a conventional antipsychotic regimen. Main outcomes were the total change in Positive and Negative Syndrome Scale score and the Brief Psychiatric Rating Scale score from baseline to end of treatment at week 24 (or at withdrawal). RESULTS Decreased plasma pentosidine levels were observed in eight patients. Two patients showed marked improvement in their psychological symptoms. A patient who harbors a frameshift mutation in the Glyoxalase 1 gene also showed considerable reduction in psychosis accompanied with a moderate decrease in plasma pentosidine levels. A reduction of greater than 20% in the assessment scale of drug-induced Parkinsonism occurred in four patients. Although there was no severe suicide-related ideation or behavior, Wernicke's encephalopathy-like adverse drug reactions occurred in two patients and were completely suppressed by thiamine supplementation. CONCLUSION High-dose pyridoxamine add-on treatment was, in part, effective for a subpopulation of schizophrenia patients with enhanced carbonyl stress. Further randomized, placebo-controlled trials with careful monitoring will be required to validate the efficacy of high-dose pyridoxamine for these patients.