title: A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes.
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.
  
  
  CONCLUSIONS
  Lack of a placebo arm and small sample size.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Venkatasubramanian
authors.forename: Channaveerachari Naveen
authors.initials: CN
authors.lastname: Kumar
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Pandey
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D010045:Outpatients; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D014803:Vitamin B Complex; D005492:Folic Acid
keywords: Augmentation; Depressive episodes; Fluoxetine; Folate; Folic acid