Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress

Masanari Itokawa, Mitsuhiro Miyashita, Makoto Arai, Takashi Dan, Katsuyoshi Takahashi, Taro Tokunaga, Kayo Ishimoto, Kazuya Toriumi, Tomoe Ichikawa, Yasue Horiuchi, Akiko Kobori, Satoshi Usami, Takeo Yoshikawa, Naoji Amano, Shinsuke Washizuka, Yuji Okazaki, Toshio Miyata

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)35-44
Number of pages10
JournalPsychiatry and Clinical Neurosciences
Issue number1
Publication statusPublished - 2018 Jan


  • advanced glycation end-products
  • carbonyl stress
  • pentosidine
  • pyridoxamine
  • schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health


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