In the United States, suicide is the third-leading cause of mortality, with a 30% increase from 2000 to 2018. This tendency may be reversed if there were an affordable, secure, generally accessible method of avoiding suicide conduct. In a nationwide pharmacoepidemiologic investigation of people who took folic acid, researchers sought to corroborate a prior signal for a reduced risk of suicide attempt after prescription fills.

The dynamic connection between folic acid (vitamin B9) prescription fills during a 24-month period, and suicidal thoughts and deliberate self-harm were investigated using a within-person exposure-only cohort approach. For individuals with private health insurance who completed folic acid prescriptions between 2012 and 2017, information was gathered from a pharmacoepidemiologic database of US medical claims (MarketScan). With a control supplement (cyanocobalamin, vitamin B12), the same analysis was performed once more. Data were examined between August 2021 and June 2022. The International Statistical Classification of Diseases, Ninth and Tenth Revisions and Clinical Modification codes are used to identify suicide attempt or purposeful self-harm leading to an outpatient visit or inpatient admission.

An analysis of 866,586 patients revealed that 704,514 (81.30%) were female and that 90,296 (10.42%) were 60 years of age or older. Overall, there were 261 suicidal events while on a folic acid prescription (5,521,597 person-months), which equates to a rate of 4.73 per 100,000 person-months, as opposed to 895 suicidal events while off folic acid (8,432,340 person-months), which equates to a rate of 10.61 per 100,000 person-months. The hazard ratio (HR) for folic acid for suicide events was 0.56 (95% CI, 0.48-0.65) after controlling for age and sex, diagnoses associated with suicidal behavior, diagnoses associated with folic acid deficiency, folate-reducing medications, history of using folate-reducing from medications and a history of suicidal events. Similar findings were obtained for the 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). The number of suicide episodes decreased by 5% per month of additional therapy (HR, 0.95; 95% CI, 0.93-0.97), according to a duration-response analysis (1-mg dose). When the same analysis was performed on cyanocobalamin, a negative control, it revealed no correlation between the two outcomes (HR, 1.01; 95% CI, 0.80-1.27).

An advantageous relationship between folic acid and decreased incidence of suicide attempts was discovered in the extensive pharmacoepidemiologic investigation. A randomized clinical study should be conducted with suicide ideation and behavior as the primary outcomes. If proven, folic acid may be an effective, cheap, and widely accessible treatment for suicidal thoughts and actions.