The Effects of Adding Folic Acid on Fluoxetine in Treatment of Major Depressive Disorder in Patients Less than 18 Years of Age

Abstract

Background: Depression is one of the most common psychiatric disorders in childhood and adolescence, imposing significant costs on the health system. This disorder causes impairment in individual, interpersonal, social, and academic functioning of patients. Various pharmacological and non-pharmacological treatments have been recommended for the treatment of this disorder. Folic acid is a supplement used in the treatment of treatment-resistant depression in adults, but information on its use in children is limited. Objectives: This study was designed to investigate the effects of adding folic acid to fluoxetine in the treatment of major depressive disorder in patients less than 18 years of age. Methods: This study is a double-blind clinical trial conducted on 50 children and adolescents referred to outpatient clinics and inpatient child psychiatry departments affiliated with the university. These patients had been unsuccessfully treated with antidepressants for at least 8 weeks. Participants were divided into two groups; one group received folic acid plus fluoxetine, and the other group received a placebo and fluoxetine in equal proportions. These individuals were evaluated for three months and assessed for changes in depression severity and changes in blood markers. Results: After 12 weeks, the severity of depression decreased in both the folic acid and placebo groups, which was statistically significant, but no statistically significant difference was observed between the two groups. Hemoglobin levels in the placebo group and MCV levels in the folic acid group also decreased significantly after 12 weeks. Conclusions: Fluoxetine, with and without folic acid, improves depression in children, and folic acid has no effect on improving depression. © 2025, Karbasi Amel and Haghshenas.