Depression is a real illness that impacts the brain: It is a serious illness caused by changes in brain chemistry. Research tells us that other factors contribute to the onset of depression, including genetics, changes in hormone levels, certain medical conditions, stress, grief or difficult life circumstances. Any of these factors alone or in combination can precipitate changes in brain chemistry that lead to depression’s many symptoms. Preliminary results suggest a relationship between vitamin B12 deficiency and increased levels of fatigue and depression in stroke patients. If these findings could be replicated in a larger and general stroke sample, this would open treatment options and may improve quality of life after stroke. High vitamin B-12 status may be associated with better treatment outcome of depression. One possible connection is the effect of vitamin B-12 on the levels of serotonin in your brain, in addition to other chemicals. Serotonin helps to regulate your mood. Low levels of serotonin may be linked to depression. However, recent research has suggested that serotonin may play a smaller role in depression than previously thought. 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). The researchers suggest people with depression take a 1-milligram supplement of B-12 daily. More research is needed to fully understand the link between B-12 and depression. Results: A total of 100 depressed patients were screened. Out of 76 patients with low normal B12 levels (76%) were randomized to the treatment group while 24 (24%) 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). Hamilton Rating Scale for Depression the Hamilton Rating Scale for Depression (HRSD), also called the Hamilton Depression Rating Scale (HDRS), abbreviated HAM-D, is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery