World Health Organization considers depression as one of the four major health problems worldwide and projections based on 2030 as the second leading cause of years of life adjusted for disability (DALYs). However, due to the widespread presence of vitamin D receptors in areas of the brain such as the hippocampus which is associated with depression, it can be taken that vitamin D is effective on depression. Based on the material and the clinical trials conducted we decided to investigate the effect of vitamin D supplementation on symptoms of treatment resistant depression in a clinical trial study on 64 patients eligible for inclusion to study which referred to Ziaeian hospital who randomly divided into two groups and placebo (n = 32 per group). The main objective of this study is to evaluate the effect of vitamin D in response to treatment of the first step of treatment resistant depression. Secondary objective was to determine the association of age with response to treatment with vitamin D - the relationship between sex and response to treatment with vitamin D - The effect of vitamin D on calcium and phosphorus and PTH levels in serum. This study is a randomized, double blind, placebo-controlled, single-center, and phase 2-3 clinical trials. Inclusion criteria: 18-65 year old patients with treatment resistant depression and known case of major depression disorder and under treatment with full dose Sertraline at least 4-6 weeks and does not respond to treatment. Also their 25-hydroxyvitamin D serum level must be lower than 50 nmol/L or les than 20 ng/ml.
Exclusion criteria: patients with medical or psychiatric illnesses associated.
Pregnant women, Lack of interest in participating in the study, and all contraindications of vitamin D, Bupropion tablets, calcium carbonate tablets.
Intervention or interventions : Pre-intervention levels of serum 25-hydroxyvitamin D, calcium, PTH, phosphorus and alkaline phosphatase measured and based on the Hamilton depression rating scale score is determined. In both groups, the full dose of sertraline tablets continues. In addition to sertraline tablets, the group of vitamin D will take bupropion 450 mg tablet daily and orally for 3 months plus vitamin D, 50,000 IU pearl 12 ones, one per week up to 8 weeks and 1 per month up to 4 months and two calcium carbonate 500 mg tablets daily for 3 months. And the placebo group will take bupropion 450 mg tablet daily and orally for 3 months plus vitamin D placebo pearl 12 ones, one per week up to 8 weeks and 1 per month up to 4 months and two calcium carbonate 500 mg tablets daily for 3 months. After a period of 3 months, serum levels of 25-hydroxyvitamin D, calcium, PTH, phosphorus, alkaline phosphatase and also rating of depression based on the Hamilton questionnaire will be measured again. And the 2 groups will compare in terms of mentioned items. To continue treating people who were taking vitamin D supplements would be reminded to take 1 vitamin D pearl per month up to 3 months due to complete 12 pieces course of medication, and then to follow up with vitamin D deficiency or improvement should refer to the internal clinic. The primary outcome is the change in the Hamilton Rating Scale.