Serum Folate, Vitamin B12, and Homocysteine in Major Depressive Disorder, Part 1: Predictors of Clinical Response in Fluoxetine-Resistant Depression

Objective: In the present study, we assessed the relationship between serum folate, vitamin B₁₂, and homocysteine levels and clinical response in patients with major depressive disorder (MDD) who had previously failed to respond to open treatment with fluoxetine 20 mg/day and were enrolled in a 4-week, double-blind trial of either (1) fluoxetine dose increase, (2) lithium augmentation of fluoxetine, or (3) desipramine augmentation of fluoxetine.

Method: Fifty-five outpatients (mean +/- SD age = 41.7 +/- 10.6 years; 50.9% women) with MDD as assessed with the Structured Clinical Interview for DSM-III-R who were enrolled in the double-blind trial had serum folate, vitamin B₁₂, and homocysteine measurements completed at baseline (prior to fluoxetine treatment initiation). Folate levels were classified as either low (<= 2.5 ng/mL) or normal. Vitamin B₁₂ levels were classified as either low (= 13.2 mmol/L) or normal. With the use of a logistic regression, we then assessed the relationship between (1) low or normal folate levels, (2) normal or low B₁₂ levels, and (3) elevated or normal homocysteine levels and clinical response to double-blind treatment. The study was conducted from November 1992 to January 1999.

Results: Low serum folate levels (chi² = 3.626, p = .04), but not elevated homocysteine (p > .05) or low vitamin B₁₂ levels (p > .05), were associated with poorer response to treatment. The response rates for patients with (N = 14) and without (N = 38) low folate levels were 7.1% versus 44.7%, respectively.

Conclusion: Low serum folate levels were found to be associated with further treatment resistance among patients with fluoxetine-resistant MDD.