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PSYCHOPHARMACOLOGY
Folic Acid Tied to a Reduction in Suicide Attempts
October 18, 2022   

Prescription folic acid was previously linked with decreased risk of suicide attempts using a novel statistical drug safety signal-generation algorithm (iDEAS study). Due to the good safety profile and low cost of folate, a recent study aimed to confirm this association in a national pharmacoepidemiologic study of patients treated with folic acid. A within-person exposure-only cohort design was used to study the association between folic acid (vitamin B9) prescription fills over a 2-year period and suicide attempts and intentional harm (suicide events). Data were collected from a database of US medical claims for patients with private health insurance who filled prescriptions from 2012 to 2017. This analysis was repeated with a control supplement, cyanocobalamin (vitamin B12), which was not linked with suicide risk in the iDEAS study. Data were collected from 866,586 patients, the majority of whom were women (81.30%). After adjusting for multiple confounding variables, the hazard ratio (HR) for the effect of folic acid on suicidal events was 0.56 (95% confidence interval [CI]=0.48-0.64), with a 5% decrease in suicidal events per month of additional treatment (1-mg dosage; HR=0.95, 95% CI=0.93-0.97). A randomized clinical trial is needed to confirm that folic acid reduces the risk of suicidal events. A potential mechanism through which folic acid may protect against suicidal events is the role of folate in the synthesis of the monoamines dopamine, norepinephrine, and serotonin (Figure).

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Figure. A potential mechanism through which folic acid supplementation reduces the risk of suicide. Folic acid is converted to the biologically active L-methylfolate, which crosses the blood-brain barrier and helps form tetrahydrobiopterin (BH4). BH4 is needed to synthesize the monoamines dopamine, norepinephrine, and serotonin. 1 L-methylfolate is FDA approved as an adjunctive treatment for treatment-resistant depression in patients with suboptimal folate levels.

References:

Gibbons RD et al. JAMA Psychiatry 2022; Epub ahead of print. Abstract.


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