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First-Episode Psychosis? Take Your Vitamins

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Reducing homocysteine levels with a vitamin cocktail has potential benefits.

Elevated homocysteine levels have been reported in schizophrenia, and homocysteine reduction by higher vitamin doses has been reported to improve symptoms in schizophrenia. In a 12-week, randomized, double-blind, placebo-controlled Australian study, researchers provided a single pill combining standard supplement doses of vitamin B6, vitamin B12, and folic acid to 100 patients with a first episode of any psychotic disorder. All patients continued their usual treatment, including antipsychotic drugs.

Vitamins, but not placebo, increased red cell folate levels and decreased homocysteine levels. At 12 weeks, the two groups showed no differences in positive and negative symptoms or overall neurocognition. However, attention/vigilance declined in placebo patients while remaining stable in vitamin patients. This benefit with supplementation was mainly evident in patients with baseline elevated homocysteine levels, patients with affective psychoses, and women, who also showed improved processing speed. In a test of four genetic variants in folate-metabolizing enzymes, no group differences were seen.


These results, combined with other earlier findings, suggest that this vitamin preparation could be helpful in higher doses to patients with elevated homocysteine levels, particularly in those with affective psychoses. The other health benefits of lowering homocysteine levels are already known. It is sometimes claimed that methylfolate is more beneficial than folate, but in this study, folate did at least enter red cells, and its effect was independent of alleles of folate-metabolizing enzymes. Little seems to be lost by suggesting the addition of supplements in high doses to patients with affective psychoses, especially women (because an effect could have been evident in men with higher doses).

Allott K et al. The vitamins in psychosis study: A randomized, double-blind, placebo-controlled trial of the effects of vitamin B12, B6 and folic acid on symptoms and neurocognition in first-episode psychosis. Biol Psychiatry 2019 Jan 9; [e-pub]. (https://doi.org/10.1016/j.biopsych.2018.12.018)

Selected references

1) Miodownik C, et al. Vitamin B6 versus mianserin and placebo in acute neuroleptic-induced akathisia: a randomized, double-blind, controlled study. Clinical Neuropharmacol. 2006.;29: 68-72.

2) Lerner VMiodownik CKaptsan ACohen HLoewenthal U, and Kotler M . Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients: a double-blind, placebo-controlled study. J Clin Psych. 2002; 63: 54-58.

3) Lerner VMiodownik CKaptsan A, et al.  Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study. American J Psych. 2011;58: 1511-1514.

4) Burghardt KJ, and Ellingrod VL.Detection of metabolic syndrome in schizophrenia and implications for antipsychotic therapy: is there a role for folate? Mol Diag  Therapy. 2013; 17: 21-30.

5) Roffman JLLamberti JSAchtyes E, et al.  Randomized Multicenter Investigation of Folate Plus Vitamin B12 Supplementation in Schizophrenia. JAMA. Psychiatry [2013[Epub ahead of print].