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

Background: Elevated homocysteine is observed in schizophrenia and associated with illness severity. The aim was to determine if vitamin B12, B6 and folic acid lowers homocysteine and improves symptomatology and neurocognition in first-episode psychosis. Whether baseline homocysteine, genetic variation, sex and diagnosis interact with b-vitamin treatment on outcomes was also examined.

Methods: Randomized, double-blind, placebo-controlled trial. One-hundred and twenty patients with first-episode psychosis were randomized to adjunctive b-vitamin supplement (containing folic acid 5mg, B12 0.4mg, B6 50mg) or placebo, taken once-daily for 12-weeks. Co-primary outcomes were change in total symptomatology (PANSS) and composite neurocognition. Secondary outcomes included additional measures of symptoms, neurocognition, functioning, tolerability and safety.

Results: B-vitamin supplementation reduced homocysteine levels (p=.003; ES=-0.65). B-vitamin supplementation had no significant effects on PANSS total (p=.749) or composite neurocognition (p=0.785). There were no significant group differences in secondary symptom domains. A significant group difference in the attention/vigilance domain (p=.024; ES=0.49) showed the b-vitamin group remained stable and the placebo group declined in performance. 14% of the sample had elevated baseline homocysteine levels, which was associated with greater improvements in one measure of attention/vigilance following b-vitamins. Being female and having affective psychosis was associated with improved neurocognition in select domains following b-vitamins. Genetic variation did not influence b-vitamin treatment response.

Conclusion: While 12-week b-vitamin supplementation may not improve overall psychopathology and global neurocognition, it may have specific neuroprotective properties in attention/vigilance, particularly in patients with elevated homocysteine levels, affective psychosis and females. Results support a personalised medicine approach to vitamin supplementation in FEP.