Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults.

Importance: Suicide is a leading cause of death in the United States, having increased more than 30% from 2000 to 2018. An inexpensive, safe, widely available treatment for preventing suicidal behavior could reverse this trend. Objective: To confirm a previous signal for decreased risk of suicide attempt following prescription fills for folic acid in a national pharmacoepidemiologic study of patients treated with folic acid. Design, Setting, and Participants: A within-person exposure-only cohort design was used to study the dynamic association between folic acid (vitamin B9) prescription fills over a 24-month period and suicide attempts and intentional self-harm. Data were collected from a pharmacoepidemiologic database of US medical claims (MarketScan) for patients with private health insurance who filled a folic acid prescription between 2012 and 2017. The same analysis was repeated with a control supplement (cyanocobalamin, vitamin B12). Data were analyzed from August 2021 to June 2022. Exposure: Folic acid prescription fills. Main Outcome and Measure: Suicide attempt 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. Results: Data on 866 586 patients were collected; 704 514 (81.30%) were female, and 90 296 (10.42%) were 60 years and older. Overall, there were 261 suicidal events during months covered by a folic acid prescription (5 521 597 person-months) for a rate of 4.73 per 100 000 person-months, compared with 895 suicidal events during months without folic acid (8 432 340) for a rate of 10.61 per 100 000 person-months. Adjusting for age and sex, diagnoses related to suicidal behavior, diagnoses related to folic acid deficiency, folate-reducing medications, history of folate-reducing medications, and history of suicidal events, the hazard ratio (HR) for folic acid for suicide events was 0.56 (95% CI, 0.48-0.65), with similar results 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). A duration-response analysis (1-mg dosage) revealed a 5% decrease in suicidal events per month of additional treatment (HR, 0.95; 95% CI, 0.93-0.97). The same analysis for the negative control, cyanocobalamin, found no association with suicide attempt (HR, 1.01; 95% CI, 0.80-1.27). Conclusions and Relevance: This large-scale pharmacoepidemiologic study of folic acid found a beneficial association in terms of lower rates of suicide attempts. 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.

Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.

BACKGROUND: Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS: At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS: Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS: Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)

Inverse association between prostatic polyunsaturated fatty acid and risk of locally advanced prostate carcinoma.

BACKGROUND: An effect of fatty acids has been implicated in men with advanced-stage prostate carcinoma and in men who have died of the disease. To evaluate the influence of fatty acids in men with prostate carcinoma at earlier stages, the authors examined the relation between prostatic concentrations of fatty acids and locally advanced prostate carcinoma in men with clinically organ-confined disease. METHODS: Fatty acids were measured by capillary gas chromatography in fresh, nonmalignant prostate tissue specimens collected during surgery from 196 men undergoing radical prostatectomy for localized prostate carcinoma. Two-sided, two-sample Student t tests compared mean concentrations in men with extraprostatic disease (pT3-4N0-1M0) with control men with organ-confined disease. Logistic regression accounted for clinical stage, prostate-specific antigen level, Gleason sum, and other factors. RESULTS: Percent total prostatic polyunsaturated fatty acid (PUFA) was found to be inversely associated with risk of locally advanced prostate carcinoma (n=52) (odds ratio [OR]=0.93, 95% confidence interval [95% CI], 0.87-0.99; P=0.035). Risk of seminal vesicle involvement accounted for this association (OR=0.86, 95% CI, 0.78-0.95; P=0.003). Percent omega-3 fatty acid (eicosapentanoic + docosahexanoic acids) and percent arachidonic acid also were found to be inversely related to the risk of seminal vesicle involvement (OR=0.52, 95% CI, 0.30-0.90; P=0.02; and OR=0.84, 95% CI,; 0.75-0.95; P=0.005, respectively). CONCLUSIONS: Prostatic PUFA levels appear to influence the risk of locally advanced prostate carcinoma in men with clinically organ-confined disease. This association may be mediated through the immune system.