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 B-12, 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 B-12, 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 (less than or equal to2.5 ng/mL) or normal. Vitamin B-12 levels were classified as either low (less than or equal to200 pg/mL) or normal. Homocysteine levels were classified as either elevated (greater than or equal to13.2 mumol/L) or normal. With the use of separate logistic regressions, we then assessed the relationship between folate, vitamin B-12, 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 13,2 (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.