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Pharmacological interventions
L-methylfolate cannot yet be recommended as an add-on treatment in schizophrenia
  1. Błażej Misiak
  1. Correspondence to Department of Genetics, Wroclaw Medical University, Wroclaw 50-367, Poland; mblazej{at}

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Commentary on: Roffman JL, Petruzzi LJ, Tanner AS, et al. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatry 2017 (Epub ahead of print: 14 Mar 2017).

What is already known on this topic

Accumulating evidence indicates that one-carbon metabolism dysregulation, manifesting in low folate levels and elevated homocysteine levels, frequently occurs in patients with schizophrenia.1 Additionally, it has been found that these metabolic alterations are associated with a higher severity of negative symptoms.2 Previous studies investigating the efficacy of supplementation strategies have found small but significant improvement of negative symptoms that might be influenced by folate-related gene polymorphisms.3–5

Methods of the study

This was a 12-week, single-site, randomised, double-blind, placebo-controlled and parallel-group trial. The study was followed by an open-label 12-week extension that was designed to assess safety outcomes. Out of 78 outpatients screened, 55 individuals with schizophrenia were finally included between May 2009 and September 2013 at an urban community mental health …

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  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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