? Vitamin D3 supplementation to prevent depression
Rationale (why care?)
It's a vitamin, must be good!
Many people already take it
Depression has one of the largest economic burdens in the world
Primary Goals
Does vitamin D3 supplementation affect risk of depression?
Spoiler: no!
Methods
Double-blind
Randomized
Placebo controlled
18,353 participants 50 and older
2011 to 2017, median treatment duration of 5.3 years
Results
No dice!
Author's Conclusion
No good!
Diving head first!
Authors
Funding and Support
Pharmavite LLC (vitamin D3) and Pronova BioPharma/BASF (Omacor fish oil)
Grants from NIMH, NCI, NHLBI
Conflict of interest
None reported
Introduction
Background and rationale
Depression: leading cause of disease burden and disability
Often undertreated in older persons
Public health priority
Hypothesis and research question
Hypothesis: high doses D3 supplementation is effective in preventing incidence or recurrence of late-life depression
Objective: to evaluate the effectiveness of high dose D3 supplementation on depression prevention
Primary outcomes: total risk of depression or clinically relevant depressive symptoms (both recurrence and incidence) and long-term trajectory of mood based on 6 annual assessments
Methods
Design
VITAL > VITAL-DEP
Double-blind, Placebo-controlled
large sample size
2x2 factorial design (?)
Recruitment
No information on method of recruitment was provided
No information on compensation
Screening
No pre-screening information was provided
inclusion criteria
appears to be no depression hx and depression hx but no tx for past 2 years
Exclusion criteria
hx of CA or CV
D3 or fish oil intake
some medical disorders: renal failure, hypercalcemia, hypo/hyper-parathyroidism,
cirrhosis, granulomatous disease
AND MORE!
Participants
18353, 9181, 9172, 9181, 9172
2000 IU/d D3, 840mg omega-3 fatty acids as placebo
even distribution
Administration
Administration regimen not discussed
Assessment and Follow up
5 year annual follow up via mailed questionnaires
follow up until end-point, death, or end of trial
Primary Analysis
designed for power >=85%, actual powah >99%!
Cumulative incidence curves
Cox proportional hazards models
linear models
Wald test (?)
Secondary Analyses
some more analyses
also post-hoc
Results
Scores
609 cases of depression in D3 group, 625 in placebo group
adjusted HR was 0.97 (95% CI, 0.87 to 1.09; Pā=ā0.62)
difference between PHQ-8 between two groups: 0.01 points; 95% CI, ā0.04 to 0.05 points
Scores 2.0
follow up vs baseline
mean change in PHQ-8 between groups
P-value
1y
-0.01
0.84
2y
0.03
0.35
3y
0.01
0.63
4y
-0.01
0.73
5y
0.03
0.40
Overall
0.01
0.72
Statistical Significant
No significance
Clinical Significance
no bueno for 25-hydroxyvitamin D
Reliability
The good
Primary outcome based on objective measures (PHQ-8)
large sample size
100% rate of completion
Double blind
Similar groups at the start of the study, treated equally except treatment
All patients analyzed
The bad
?
The ugly
?
Generally Reliable
Conclusion
Statistical Interpretation
There isn't much room for artistic interpretation
laaaarge P-value = no statistical significance
Limitations
annual PHQ-8s
self-reported mood and depression variables were of uncertain validity
good baseline D3 levels
Conclusion
No Bueno! :(
Conclusion 2.0
These findings do not support the use of vitamin D3 in adults to prevent depression.
Discussion
Results appropriately interpreted
Adequately explained limitations except
Medication administration process
Consistent conclusion
Generalizable? Not quite
Ethnicity, age
Literature correspondence? Yes
Vitamin D supplementation and depression prevention