Folic Acid Decreases Rate of Suicidal Attempts


A duration-response analysis of 1-mg dosage produced a 5% decrease in suicidal events per month of additional treatment.

Folic Acid Decreases Rate of Suicidal Attempts

Robert D. Gibbons, PhD

Folic acid prescriptions result in a significant drop in suicide attempts and overall suicidal events, according to new research.

A team, led by Robert D. Gibbons, PhD, University of Chicago, confirmed a previous signal for a decreased risk of suicide attempts after prescription fills for folic acid.

An Increasing Problem

Overall, suicides have increased by more than 30% in the US between 2000-2018.

“An inexpensive, safe, widely available treatment for preventing suicidal behavior could reverse this trend,” the authors wrote.

In the national pharmacoepidemiologic study, the investigators examined data from 866,586 patients treated with folic acid with a within-person exposure only cohort design to identify the dynamic association between folic acid prescription fills over a 24-month time period and suicide attempts and intentional self-harm.

Of the more than 850,000 patients with data included in the analysis, 81.30% (n = 704,514) were female and 10.42% (n = 90,296) were aged 60 years or older.

The team used a pharmacoepidemiologic database of US medical claims to identify patients with private health insurance who filled a folic acid prescription between 2012-2017. They then repeated the analysis with a control supplement of cyanocobalamin.

The investigators sought main outcomes of suicide attempts or intentional self-harm resulting in an outpatient visit or inpatient admission as identified by codes from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification.

The Impact of Folic Acid

The analysis shows 261 suicidal events during months covered by a folic acid prescription (5,512,597 person-months. The rate of suicidal events was 4.73 events per 100,000 person-months. This was lower than the 895 suicidal events during months without folic acid (8,432,340 person-months) for a rate of 10.61 suicidal events per 100,000 person-months.

After adjusting for age and sex, the investigators found diagnoses related to suicidal behavior, folic acid deficiency, folate-reducing medications, history of folate-reducing medications, and history of suicidal events yielded a hazard ratio for folic acid for suicide events of 0.56 (95% CI, 0.48-0.65).

There were similar results for modal dosage of 1 mg of folic acid per day (HR, 0.57; 95% CI, 0.48-0.69) and women of childbearing age (HR, 0.60; 95% CI, 0.50-0.73).

However, a further duration-response analysis of 1-mg dosage produced a 5% decrease in suicidal events per month of additional treatment (HR, 0.95; 95% CI, 0.93-0.97) and the same analysis for cyanocobalamin showed no association with suicide attempts (HR, 1.01; 95% CI, 0.80-1.27).

“This large-scale pharmacoepidemiologic study of folic acid found a beneficial association in terms of lower rates of suicide attempts,” the authors wrote. “The results warrant the conduct of a randomized clinical trial with suicidal ideation and behavior as outcomes of interest. If confirmed, folic acid may be a safe, inexpensive, and widely available treatment for suicidal ideation and behavior.”

The study, “Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults,” was published online in JAMA Psychiatry.

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