A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes

• Published in: Journal of affective disorders 2013-09, Vol.150 (2), p.644-648
• Main Authors: Venkatasubramanian, Ramakrishnan, Kumar, Channaveerachari Naveen, Pandey, Ravi Shankar
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Affective disorders; Antidepressant drugs; Antidepressive Agents, Second-Generation - therapeutic use; Augmentation; Biological and medical sciences; Depression; Depressive Disorder, Major - drug therapy; Depressive episodes; Dosage; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Fluoxetine - therapeutic use; Folate; Folic acid; Folic Acid - therapeutic use; Humans; Medical sciences; Mood disorders; Neuropharmacology; Outpatients; Pharmacology. Drug treatments; Psychiatric Status Rating Scales; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Treatment Outcome; Vitamin B Complex - therapeutic use
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2013.02.029

Abstract Background Though encouraging evidence exists for the use of folic acid as an augmenting agent to antidepressants, evidence regarding its optimal dosage is lacking. Methods Forty-two female out-patients with moderate (with or without somatic syndrome) or severe depressive episodes (without psychotic symptoms) diagnosed as per ICD-10 criteria, were randomized in a double-blind fashion to receive either 20 mg fluoxetine and a relatively low dose folic acid (1.5 mg/day; n =23; Group I) or 20 mg fluoxetine and high dose folic acid (5 mg/day; n =19; Group II). Primary outcome measures were weekly changes of scores on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) for 6 weeks. Results Group II patients showed greater improvement in both HDRS [Mean (SD) baseline HDRS score=21 (2.3) for group I and 20.0 (1.4) for group-II; time X group interaction effect: p =0.01] and BDI [Mean (SD) baseline BDI score=25.1 (5.2) for group-1 and 23.1 (2.7) for group-II; time X group interaction effect: p =0.01]. With regard to HDRS, 7 (36.8%) group II patients remitted compared to 2 (8.7%) group I patients ( p =0.03); 9 (47.4%) patients of group II responded when compared to 6 (26.1%) from group I ( p =0.15). When BDI was considered, 5 (26.3%) group II patients remitted when compared to 2 (8.7%) from group I ( p =0.13); 10 patients (52.6%) from group II responded when compared to 5 (21.7%) from group I ( p =0.04). No adverse effects were noted in either group. Limitations Lack of a placebo arm and small sample size. Conclusion Compared to folic acid 1.5 mg/day, augmentation with 5 mg/day may be more beneficial in female patients with depressive episodes taking fluoxetine 20 mg/day.