Vitamin B12 Supplementation in Treating Major Depressive Disorder: A Randomized Controlled Trial

Ehsan Ullah Syed2, Mohammad Wasay1, *, Safia Awan1, *
1 Department of Psychiatry and Medicine (Neurology), Aga Khan University, Karachi, Pakistan
2 Department of Psychiatry Penn State Milton S Hershey Medical Center Penn State College of Medicine, Hershey, PA, USA

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© Syed et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to these authors at the Department of Medicine/ Neurology, The Aga Khan University, Stadium Road, Karachi 74800, Pakistan; Tel: (9221) 4930051; Ext: 4665, 4681; Fax: (9221) 4934294; E-mail:;



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.


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).


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).


Vitamin B12 supplementation with antidepressants significantly improved depressive symptoms in our cohort.

Keywords:: Depression, vitamin B12, antidepressants, RCT.