Randomized Multicenter Investigation of Folate Plus Vitamin B12Supplementation in Schizophrenia
| Autor: | Eric D. Achtyes, Lisa Raeke, Donald C. Goff, Michele Hill, Jordan W. Smoller, Noah J. Silverstein, Eric A. Macklin, Joshua L. Roffman, J. Steven Lamberti, Gail C. Galendez |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Glutamate Carboxypeptidase II Male medicine.medical_specialty Adolescent Placebo Article law.invention Young Adult Folic Acid Double-Blind Method Randomized controlled trial law Internal medicine medicine Humans Vitamin B12 Young adult Scale for the Assessment of Negative Symptoms Aged Positive and Negative Syndrome Scale business.industry Middle Aged medicine.disease Surgery Clinical trial Vitamin B 12 Psychiatry and Mental health Treatment Outcome Schizophrenia Drug Therapy Combination Female business |
| Zdroj: | JAMA Psychiatry. 70:481 |
| ISSN: | 2168-622X |
| Popis: | Importance More effective treatments are needed for negative symptoms of schizophrenia, which are typically chronic, disabling, and costly. Negative symptoms have previously been associated with reduced blood folate levels, especially among patients with low-functioning variants in genes that regulate folate metabolism, suggesting the potential utility of folate supplementation. Objectives To determine whether folic acid plus vitamin B 12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response. Design Parallel-group, randomized, double-blind, placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B 12 . Setting Three community mental health centers affiliated with academic medical centers in the United States. Participants Outpatients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment. Eligible patients were 18 to 68 years old, were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more, and scored 60 or more on the Positive and Negative Syndrome Scale. Intervention One hundred forty subjects were randomized to receive daily oral folic acid plus vitamin B 12 or placebo. Main Outcome Measures Change in negative symptoms (Scale for the Assessment of Negative Symptoms [SANS]), as well as positive and total symptoms (Positive and Negative Syndrome Scale). Results Folate plus vitamin B 12 improved negative symptoms significantly compared with placebo (group difference, −0.33 change in SANS score per week; 95% CI, −0.62 to −0.05) when genotype was taken into account but not when genotype was excluded. An interaction of the 484C>T variant of FOLH1 (rs202676) with treatment was observed (P = .02), where only patients homozygous for the 484T allele demonstrated significantly greater benefit with active treatment (−0.59 change in SANS score per week; 95% CI, −0.99 to −0.18). In parallel, we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load (P = .03), which persisted until 8 weeks of treatment. Change in positive and total symptoms did not differ between treatment groups. Conclusions Folate plus vitamin B 12 supplementation can improve negative symptoms of schizophrenia, but treatment response is influenced by genetic variation in folate absorption. These findings support a personalized medicine approach for the treatment of negative symptoms. Trial Registration clinicaltrials.gov Identifier: NCT00611806 |
| Databáze: | OpenAIRE |
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