Vitamin B12 Supplementation in Treating Major Depressive Disorder: A Randomized Controlled Trial
What this study found
Vitamin B12 augmentation improved depressive symptoms compared with antidepressants alone in this low-normal B12 subgroup. At 3 months, a 50% reduction in HAM-D score occurred in 44.1% of the vitamin B12 group versus 5.1% of controls (p<0.001 unadjusted; p<0.001 adjusted), and the mean HAM-D change was 11.09 ± 4.58 versus 5.00 ± 3.38 (p<0.001 unadjusted; p<0.001 adjusted). Follow-up HAM-D scores were also lower in the vitamin B12 arm after adjustment (12.12 ± 5.12 vs 14.38 ± 4.73; p<0.001). No adverse effects or complications were noted in either group.
- Study & population
- Randomized controlled trial in outpatient adults with major depressive disorder and low normal vitamin B12 levels (190 to 300 pg/ml) who had not responded adequately to an initial SSRI.
- Intervention
- Vitamin B12 augmentation consisted of intramuscular injectable vitamin B12, 1000 mcg once weekly for 6 weeks, given alongside ongoing antidepressant therapy.
- Key limitation
- The trial was small, single-center, and conducted in a specific subgroup of depressed outpatients with low normal B12, which limits generalizability.
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Open PDFOriginal abstract
Background/Objective: Recent literature has identified links between vitamin B12 deficiency and depression.We compared the clinical response of SSRI-monotherapy with that of B12-augmentation in a sample of depressed patients with low normal B12 levels who responded inadequately to the first trial with the SSRIs. Methods: Patients with depression and low normal B12 levels were randomized to a control arm (antidepressant only) or treatment arm (antidepressants and injectable vitamin B12 supplementation). Results: A total of 199 depressed patients were screened. Out of 73 patients with low normal B12 levels 34 (47%) were randomized to the treatment group while 39 (53%) were randomized to the control arm. At three months follow up 100% of the treatment group showed at least a 20% reduction in HAM-D score, while only 69% in the control arm showed at least a 20% reduction in HAM-D score (p<0.001). The findings remained significant after adjusting for baseline HAM-D score (p=0.001). Conclusion: Vitamin B12 supplementation with antidepressants significantly improved depressive symptoms in our cohort.