Serum Folate, Vitamin B12, and Homocysteine in Major Depressive Disorder, Part 2: Predictors of Relapse During the Continuation Phase of Pharmacotherapy

Objective: In the present study, we assessed the relationship between serum folate, vitamin B₁₂, and homocysteine levels on the rate of relapse in outpatients with remitted major depressive disorder (MDD) during a 28-week continuation phase of treatment with fluoxetine.

Method: Seventy-one outpatients (mean +/- SD age = 40.2 +/- 11.1 years; 56.3% women) with MDD (as assessed with the Structured Clinical Interview for DSM-III-R) who had remitted and who were enrolled in the continuation phase of treatment with fluoxetine had serum folate, vitamin B₁₂, and homocysteine measurements completed at baseline (prior to acute-phase treatment). Patients were followed for 28 weeks of continued treatment with fluoxetine 40 mg/day to monitor for depressive relapse. 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 separate logistic regressions, we then assessed the relationship between folate, vitamin B₁₂, and homocysteine level status and relapse. The study was conducted from November 1992 to January 1999.

Results: The presence of low serum folate levels (p = .004), but not low B₁₂ (p > .05) or elevated homocysteine levels (p > .05), was associated with relapse during continuation treatment with fluoxetine. The relapse rates for patients with (N = 7) and without (N = 64) low folate levels were 42.9% versus 3.2%, respectively.

Conclusion: Low serum folate levels were found to place patients with remitted MDD at risk for depressive relapse during the continuation phase of treatment with fluoxetine.