VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL

Mood scores are evaluated by the 8-item Patient Health Questionnaire (PHQ-8). The measured outcome was the total PHQ-8 score. The PHQ-8 includes items corresponding to the criteria for major depression. Each of the 8 items can be scored as 0, 1, 2, or 3 points (higher score means worse symptoms). The 8 items are summed to a total PHQ-8 score. The range for the PHQ-8 score is 0-24 points; higher scores denote worse mood or depressive symptoms. The PHQ-8 was measured annually at baseline and at up to 5 follow-up times (for a maximum of 6 time points). Data from all time points was used to determine the mean differences in change in mood scores over all follow-up by randomized treatment. Per protocol, the Statistical Analysis section shows the results for the primary outcome of mean difference in overall change in PHQ-8 scores comparing active and placebo groups (for each agent).

Time frame: Baseline, follow-up year 1, follow-up year 2, follow-up year 3, follow-up year 4, and follow-up year 5

Population: Analysis population reflects the randomized groups by treatment agents, as all published analyses per protocol were conducted comparing active treatment to placebo. These were n=9181 randomized to active vitamin D; n=9172 randomized to vitamin D placebo; n=9171 randomized to active fish oil; n=9182 randomized to fish oil placebo. Per intervention results are presented for active treatment vs placebo. Each row shows exact number of participants providing responses to the PHQ-8 at that timepoint.

Depression syndrome will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (e.g., PHQ) items. This is an event outcome, where the depression event was defined as a new self-report of physician/clinician-diagnosed depression, treatment (medication and/or counseling) for depression, or presence of clinically relevant depressive symptoms (PHQ-8 total score \>=10 points) on the annual study questionnaires that were administered over a median 5.3 years of randomized treatment and follow-up. Participants were followed for the depression event until the occurrence of the endpoint, death, or the end of the trial, whichever came first. The Outcome Measure table shows the counts of depression events in each randomized group by treatment.

Time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up

Population: Analysis population reflects the randomized groups by treatment agents, as all published analyses per protocol were conducted comparing active treatment to placebo. These groups were: n=9181 randomized to active vitamin D and n=9172 randomized to vitamin D placebo; n=9171 randomized to active fish oil and n=9182 randomized to fish oil placebo. Per intervention results are presented for active vitamin D vs. matching vitamin D placebo and for active fish oil vs. matching fish oil placebo.

Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 \>=10 points).

Time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up

Population: Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 \>=10 points). Among the n=18,353 participants randomized, there were n=16657 without a history of depression at baseline and therefore at risk for incident depression.

Post-hoc Outcome. Recurrent depression is defined as depression cases that occurred among those with past history of depression, but not under treatment or active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 \>=10 points).

Time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up

Population: Post-hoc Outcome. Recurrent Depression is defined as depression cases that occurred among those with past history of depression, but not active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 \>=10 points). Among n=18,353 randomized, n=1696 were eligible for recurrent depression.