There is a thought-provoking editorial in the openly-accessible Journal of Psychiatry of Neuroscience (JPN): Has the time come for clinical trials on the antidepressant effect of vitamin D?
(45 KB PDF). In it, the editor of the the Journal, Simon N.
Young, PhD, argues that there is enough evidence to justify increased
He points to a recent article in the Archives of General Psychiatry to support this view:
Depression Is Associated With Decreased 25-Hydroxyvitamin D and Increased Parathyroid Hormone Levels in Older Adults
Witte J. G. Hoogendijk, MD, PhD; Paul Lips, MD, PhD; Miranda
G. Dik, PhD; Dorly J. H. Deeg, PhD; Aartjan T. F. Beekman, MD, PhD;
Brenda W. J. H. Penninx, PhD
Arch Gen Psychiatry. 2008;65(5):508-512.
Context Depression has incidentally been
related to altered levels of 25-hydroxyvitamin D [25(OH)D] and
parathyroid hormone (PTH), but this relation has never been studied
Objective To determine in a large population-based
cohort whether there is an association between depression and altered
25(OH)D and PTH levels…
Main Outcome Measure Depression was measured using
self-reports (Center for Epidemiologic Studies-Depression scale) and
diagnostic interviews (Diagnostic Interview Schedule). Levels of
25(OH)D and PTH were assessed. Potentially confounding factors (ie,
age, sex, smoking status, body mass index, number of chronic
conditions, and serum creatinine concentration) and explanatory factors
(ie, season of data acquisition, level of urbanization, and physical
activity) were also measured.
Results Levels of 25(OH)D were 14% lower in 169 persons
with minor depression and 14% lower in 26 persons with major depressive
disorder compared with levels in 1087 control individuals (P <
.001). Levels of PTH were 5% and 33% higher, respectively (P = .003).
Depression severity (Center for Epidemiologic Studies Depression Scale)
was significantly associated with decreased serum 25(OH)D levels (P =
.03) and increased serum PTH levels (P = .008).
Conclusion The results of this large population-based
study show an association of depression status and severity with
decreased serum 25(OH)D levels and increased serum PTH levels in older
Of course finding a correlation does not say anything about
causation. Even if it did say something about causation, it would
not necessarily imply anything about treatment. Young points out
that most research on the potential antidepressant effect of Vitamin D
supplementation is not very helpful. He cites two studies that
had adequate design, but both used subjective feelings of positive
affect or well-being as outcome measures. That is nice, but not
informative with regard to treatment of clinically significant
He mentions a few other theoretical considerations, then concludes:
Treatment of depression with vitamin D is an idea worth
testing in carefully selected populations. This includes those with low
vitamin D levels, especially the elderly, who have an increased
incidence of low vitamin D, and patients with seasonal affective
disorder who do not respond to light therapy. If there are patients in
whom vitamin D is an effective antidepressant, this is likely to be one
of the most costeffective treatments in psychiatry, and one with
negligible side effects.
Note that he specifically is not arguing that vitamin D supplementation
should be considered as anywhere near clinically validated for
treatment. Rather, he is suggesting that it might be worth
pursuing in limited settings.
Also note that JPN is a Canadian journal. As Razib pointed out
a while ago, vitamin D deficiency is common among non-white persons in
Canada. Perhaps that is where some of the interest comes
from. The authors of the Arch Gen Psychiatry article are from the
Netherlands, another high-latitude country.
Dr. Young points out that the best evidence regarding mood
effects of vitamin D shows only that it perks some people up a
bit. So how does he use that as a basis to say that he ought to
study it more?
Well, I can’t speak for him, but since this is my blog, I happily will
speak for myself. First, I would be skeptical of the notion that
vitamin D will be found to be an “effective antidepressant” in the
usual sense. That is, if it were given as a sole treatment in a
randomized double-blind clinical trial, compared with placebo and and
active comparator, I doubt it would be very impressive. You never
know until you try, but I still doubt it.
However, that does not mean we should forget it. Not at
all. Even if all it does is to perk people up a little bit, it
still could be a useful part of our armamentarium. The reason is
this: in the treatment of depression, with antidepressants, it is
common for people to show significant improvement, while not attaining
full remission. For example, let’s say you have a moderately
severe depression, with a BDI score
of 28. You start of sertraline, get up to a dose of 200mg for six
weeks. You get 50% better. Your BDI is now 14. You
can function OK, but there are problems. For one, you are not at
your best, probably still fairly unhappy, fairly often. Two, you
are running a higher risk of relapse back into a full episode.
In such a situation, there are many things you could do, and it is
likely that you eventually would find some intervention to get that
score down to 7 or so, which would be a remission.
But, there are some people who go through a lengthy course of
interventions, often two or three at a time, but never quite get
there. The way I see it, you might get a 50% improvement with the
medication. Then maybe you have the energy to start regular
exercise, and you get another 5%. You start eating better, and
get another 5%. You join a volunteer group, get another 5%.
And so forth. Some people need a lot of those 5% increments of
improvement. I suspect that our medical-industrial complex
discards a lot of things that are like that: a little bit helpful, but
with no potential to be a blockbuster.
The FDA will never approve something that results in only a 5%
improvement. Especially if it can’t be patented. But those
little things can be important. In selected populations, perhaps
vitamin D would give a boost of a lot more than 5%. I’m
particularly curious about the people who don’t respond to bright light
treatment. The lights used for this treatment are filtered so the
patient is not exposed to ultraviolet light. We think that is
good, but maybe it reduces the effect for some people.