11 January 2018
Masanari Itokawa (CMRC), Mitsuhiro Miyashita (Schizophrenia Research Project) published a paper on “Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress.” in Psychiatry and clinical neuroscience.
【Aim】 We previously reported that increased pentosidine (enhanced carbonyl stress) is associated with a subpopulation of patients with schizophrenia. Pyridoxamine, one of the three forms of vitamin B6, is able to entrap pentosidine and excrete them. The aim of this clinical study is to obtain proof of concept of high-dose pyridoxamine as a novel treatment option for schizophrenia with enhanced carbonyl stress.
【Methods】 Ten Japanese patients diagnosed as schizophrenia showing high plasma pentosidine were recruited in a 24 week, open trial in which high-dose pyridoxamine (ranging from 1200 to 2400 mg/day) was added on a conventional anti-psychotic regimen. Major Outcomes were the total change in Positive and Negative Syndrome Scale (PANSS) score and the Brief Psychiatric Rating Scale (BPRS) score from baseline to end of treatment at week 24 (or at withdrawal). Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and Columbia-Suicide Severity Rating Scale (C-SSRS) were evaluated to determine the severity of extrapyramidal symptoms (EPS) and the occurrence of suicide related adverse events
【Results】 Decrease of 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 (GLO1) gene also showed moderate reduction in psychosis with a considerable decrease in pentosidine levels. An improvement of drug induced Parkinsonism occurred in four patients. Although there was no severe suicide associated ideation or behavior, Wernicke’s encephalopathy-like adverse drug reactions occurred in two patients, which was completely suppressed by rapid thiamine supplementation.
【Conclusion】 High-dose pyridoxamine add-on treatment may be, in part, effective for schizophrenia with enhanced carbonyl stress. Further randomized, placebo controlled study with should be required to confirm the efficacy of high-dose pyridoxamine for these patients.