Tuesday, September 2, 2008

B Vitamins, Folic Acid Do Not Reduce Depression Incidence, Severity CME

Medscape Medical News

News Author: Caroline Cassels
CME Author: Désirée Lie, MD, MSEd

August 25, 2008 — Supplementation with B vitamins appears to be no better than placebo in reducing the incidence of depression or depressive symptoms, new research suggests.

A randomized, double-blind, placebo-controlled trial of 299 older men showed treatment with vitamins B12, B6, and folic acid produced no significant change in mood for 2 years.

"We investigated the association between vitamin use and depression in 3 different ways, none of which showed an advantage of B vitamins compared with placebo over 24 months: change in Beck Depression Index [BDI] scores, incidence of clinically significant depressive symptoms, and remission of depression," the authors write.

With first author Andrew H. Ford, MBBS, from South Metropolitan Health Service, in Perth, Australia, the study is published in the August issue of the Journal of Clinical Psychiatry.

Previous research has linked lower concentrations of B vitamins and folate to depression. However, many of these reports have been observational and or confounded by the fact that participants were receiving antidepressants.

Prospective Design

The purpose of the current study was to prospectively determine whether treatment with B vitamins during an extended period reduced the onset of clinically depressive symptoms in a cohort of men aged 75 years and older.

For the study, investigators recruited a random sample of 299 subjects who were participants in a large population-based study of abdominal aortic aneurysm screening.

All subjects were being treated for or had a history of hypertension. Individuals were excluded from the study if they had a BDI score of 18 or higher and significant cognitive impairment, as determined by a Mini-Mental State Examination (MMSE) score of less than 24. In addition, individuals who were already taking B vitamins were excluded from the study, which was conducted from June 2001 to June 2004.

Participants were randomized to receive a single oral capsule containing 400 µg B12, 2 mg folic acid, and 25 mg B6 or an identical-looking placebo capsule. Study subjects were told to consume 1 capsule every morning for 2 years.

Study subjects and investigators were blinded to group membership until the last follow-up assessment was completed.

The study's primary outcome was changes in BDI scores during the study period. The researchers also examined the proportion of individuals who were free of clinically significant depressive symptoms at baseline, but they became depressed during the trial.

A total of 149 and 150 subjects were in the placebo and active-treatment groups, respectively. With a 19.4% dropout rate, the final analysis was based on the 241 who completed the 2-year trial.

Role as Adjunctive Therapy?

The study revealed that participants in the active-treatment group were 24% more likely to remain free of depression during the trial, but the difference between the groups was not significant.

Among 23 men — 12 in the vitamin group and 11 in the placebo cohort — who had mild to moderate depression, there was no difference between the 2 groups after 24 months of treatment.

Investigators also found that participants in the active-treatment group had increased blood levels of B12 and folate and reduced levels of plasma homocysteine. They also found that these blood levels were similar in men with and without depression, a finding that suggests the potential link between low vitamin B levels, high homocysteine, and depression is not strong.

"It remains to be determined whether vitamin supplementation would be an effective adjunctive antidepressant treatment for people with severe depression, and if women would benefit more than men from this therapeutic approach," they write.

The authors have disclosed no relevant financial relationships.

J Clin Psychiatry. 2008;69:1203-1209.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:

1. Describe the effect of vitamin B supplementation on symptoms of depression in elderly men.
2. Describe the effect of vitamin B supplementation on the likelihood of new depressive symptoms in elderly men.

Clinical Context

Depression is a leading cause of disability, affecting 2% to 5% of the adult population. Some preliminary evidence suggests that deficiencies of vitamin B contribute to the onset and maintenance of depression and its symptoms through an effect on the risk for cerebrovascular disease, and cross-sectional studies suggest that patients with depression may have lower serum levels of B vitamins compared with adults without depression.

This is a 2-year, double-blind, randomized clinical trial conducted in elderly men who were originally recruited as part of a population-based study of abdominal aneurysm screening. The study assesses the role of vitamin B supplementation on depression and new onset depressive symptoms.
Study Highlights

* Included were 299 men aged 75 years or older with a history of hypertension from a pool of 12,203 men in the original abdominal aneurysm screening study in 1 city in Australia.
* The men had been identified from the electronic electoral roll.
* Excluded were those with a BDI score of 18 or higher or significant cognitive impairment defined as MMSE score lower than 24, those with serious illness, and those who were taking vitamin B supplements.
* 150 were randomized to treatment consisting of 1 capsule of 400 μg B12, 2 mg folic acid, and 25 mg B6 daily, previously shown to be effective in lowering homocysteine levels; and 149 were randomized to identical-looking placebo 1 capsule daily for 2 years.
* Assessments occurred at baseline, 6, 12, 18, and 24 months.
* MMSE was used to assess cognitive function.
* Hazardous alcohol intake was defined as more than 4 standard drinks at least 4 times weekly or more than 6 drinks on any single day.
* Primary outcome was BDI score consisting of 21 questions scoring from 0 to 3 each, with scores ranging from 0 to 63.
* BDI scores were categorized in 4 groups of “no to minimal depression,” “mild to moderate depression,” “moderate to severe depression,” and “severe depression.”
* Other outcomes were increase in BDI scores, scores greater than 9 (suggestive of at least mild depressive symptoms), and new onset depressive symptoms.
* Fasting samples were taken for serum B12, total plasma homocysteine, and red cell folate levels.
* Mean age was 79 years, and 8.7% to 13.4% were considered to ingest harmful levels of alcohol.
* The dropout rate was 19.4% with the final analysis based on 241 participants.
* There was no difference between the 2 groups in BDI scores over time or change of scores in each group over time.
* When proportion with BDI scores of 10 or higher were examined, the vitamin B group was 24% more likely to remain free of depressive symptoms (hazard ratio, 1.24), but this was not statistically significant.
* At the end of the study, 79.1% of those receiving vitamin B vs 84.3% of those taking placebo remained free of depression.
* There was no difference in concentrations of B12 and red cell folate or homocysteine levels among men with and without depression.
* The authors concluded that treatment with vitamin B during 2 years was not better than placebo at reducing severity of depressive symptoms or reducing new onset of depressive symptoms in elderly men.
* The authors noted that the effect of vitamin B supplementation as an adjunctive treatment in depression was not known and deserved further investigation.

Pearls for Practice

* Supplementation with vitamin B for 2 years is not associated with reduced depressive symptoms in elderly men.
* Supplementation with vitamin B for 2 years is not associated with lower risk for new onset depressive symptoms in elderly men.

According to this study, which of the following best describes the effect of vitamin B supplementation for 2 years on depressive symptoms in elderly men?
Reduces BDI score
Reduces BDI score only in the first year
No change in BDI score
Reduces BDI score only in the second year

Which of the following best describes the effect of vitamin B supplementation for 2 years on new onset depressive symptoms in elderly men?
Lower risk of new-onset depression
No effect on new-onset depressive symptoms
Lower risk for suicide
Lower risk for depressive symptoms only in those with low folate levels
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CME Author

Désirée Lie, MD, MSEd
Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California

Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

Brande Nicole Martin
is the News CME editor for Medscape Medical News.

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