Difficulties with subject enrolment.

Low levels of vitamin D have been associated with depression. This study will test if a vitamin D supplement is helpful in patients with depression who have not found relief with the use of anti-depressant medication. Participants will continue to take their medication plus vitamin D or placebo for 8 weeks. The investigators will monitor their depression symptoms and the investigators think that the people taking vitamin D may have an improvement in their symptoms.

It is hypothesized that deficient or insufficient levels of vitamin D may play a role in the pathogenesis of depression and that supplemental vitamin D may have an antidepressant effect -either through a direct action on the brain or though correction of a deficiency state. The investigators hypothesize that eight weeks of vitamin D supplementation will produce a statistically significant decrease in symptoms of depression compared to placebo for people with non-remitted depression.

This study will be a randomized, double-blind placebo-controlled study. Individuals will be recruited who have failed to achieve remission from a depressive episode after a minimum of eight weeks of treatment with a first-line antidepressant, at an adequate dose. They will be randomized to receive either placebo or vitamin D supplementation in addition to their anti-depressant medication, which they will continue to take at the same dose for the duration of the eight week study.There will be an additional follow up visit one month later.

The primary objective is to evaluate the efficacy of supplemental vitamin D as an adjunctive treatment in the management of non-remitted depression compared to placebo. Additionally, its safety and tolerability will be assessed.

A secondary objective will be to assess the relationship between changes in serum vitamin D levels and mood in order to elucidate information about the role that reversal of vitamin D deficiency may play in the treatment of this condition.

Inclusion Criteria:

Patients who meet the following criteria are eligible for enrolment in this trial:

1. Men or Women aged 18 to 65 (extremes included) who are out-patients
2. Patients with a primary diagnosis of Major Depressive Disorder (MDD) according to the DSM-IV-TR criteria (16), confirmed using the Mini International Neuropsychiatric Interview (MINI)
3. Patients who have failed to respond to treatment with a single pharmacological antidepressant agent at an adequate dose as defined by a lack of remission from the current depressive episode (score of 7 or less on the Hamilton Depression Scale) after eight weeks of treatment
4. On the basis of a physical examination, medical history and basic laboratory screening, the patient is, in the investigators opinion, in a suitable condition
5. Willing and able to attend study appointments in the correct time windows

Exclusion Criteria:

Patients meeting one or more of the following criteria cannot be selected for inclusion:

1. Any other Axis I disorder that was a primary disorder in the past 6 months. Co-morbid anxiety disorders will be permitted as long as MDD is judged to be the primary diagnosis.
2. Current or past mania or hypomania or a mixed mood disorder phase suggestive of a bipolar mood disorder as defined by the DSM-IV-TR (16)
3. Current or past psychotic disorder
4. Diagnosis of a mental retardation, dementia or other cognitive disorder
5. Current or past alcohol or drug use as defined in the DSM-IV-TR (16) in the last six months
6. Commencement of formal psychotherapy 30 days prior to Screening (formal psychotherapy for study purposes includes Cognitive Behavioural Therapy (CBT) or acute CBT treatment in individual therapy)
7. Current use of psychiatric medication other than the antidepressant to which the patient failed to show sufficient response. Short half-life hypnotics (anxiolytics) will be allowed p.r.n. in the evening for the treatment of insomnia
8. Patient using herbal or nutritional treatments judged to have anti-depressant effects unless they have discontinued its use with their physician's consent more than 2 weeks prior to entry into the study
9. Clinical interpretation of apparent suicide risk
10. Supplementation of vitamin D >200IU per day in the past 6 months
11. Baseline serum vitamin D of >150nmol/L
12. A history of parathyroid disease or kidney stones
13. Pregnant or breast-feeding females
14. Serious medical illness: Liver or renal insufficiency, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic or metabolic disturbance, diabetes, dyslipidemia and hypertension;or in the judgment of investigator as not being appropriate for the study on medical grounds
15. The patient is, in the opinion of the investigator, unlikely to be able to comply with the clinical trial protocol, or is unsuitable for any other reasons.