Acid Folic Supplementation in Major Depressive Disorder Treatment: A Double-Blind Randomized Clinical Trial

Background Augmentation therapy involves the addition of a second drug, such as mood stabilizers, antipsychotics, and nutritional supplements, to a primary antidepressant treatment. Studies on adding folic acid to a preexisting antidepressive regimen as a form of augmentation therapy have had different and even controversial results. Objectives This study aimed to determine the effects that adding folic acid to a pharmaceutical diet with citalopram has on the treatment of depression. Methods This double-blind randomized clinical trial was conducted in Kashan, Iran on 90 patients who suffered from depression. Patients were allocated to study groups using random permuted blocks. One group (n = 45) received a dosage of 20 mg citalopram in combination with 2.5 mg folic acid on a daily basis, and the other group (n = 45) received the same daily dose of citalopram with a placebo for eight weeks. To measure the severity of each patient’s depression, the Beck depression inventory II (BDI-II) questionnaire was used prior to starting the antidepressant therapy and was repeated four, six, and eight weeks after beginning the treatment. A reduction from the original BDI-II scores that was greater than 50% was considered to be a response to treatment. Results The average depression scores before treatment were 30.11 ± 10.41 in the intervention group and 31.24 ± 10.26 in the control group (P = 0.6). At the end of the study, the depression scores in the intervention and the control groups were 13.31 ± 6.57 and 19.11 ± 8.59, respectively (P < 0.001). A reduction in the average depression scores of the intervention group was statistically significant after six and eight weeks (P = 0.01 and P = 0.001, respectively). At the end of the study, the frequency of response to treatment was 73.3% in the intervention group and 40.0% in the control group (P < 0.001). Conclusions Folic acid, when used as a complementary therapy, can improve a patient’s response to antidepressants used for the treatment of major depression.