Depression and Smoking Pose Similar Risks for Mortality

Pauline Anderson

August 14, 2009

August 14, 2009 — Depression is on a par with smoking when it comes to increasing risks for mortality, although anxiety may counteract some of this increased risk, according to a new study.

"We were a bit surprised to find that depression — and not necessarily at a severe level — is associated with mortality at the same strength as smoking," lead author Arnstein Mykletun, PhD, from the University of Bergen, Norway, told Medscape Psychiatry. "Perhaps one of the more important new findings is that depression is that strong, even taking into account a lot of potential confounding factors including health status," he added.

Whereas other studies have linked depression with mortality, Dr. Mykletun said this study is more comprehensive and also is large enough to be able to address all of these factors.

The study is published in the August issue of the British Journal of Psychiatry.

Strong Association

British and Norwegian researchers used information gathered in the Health Study of Nord-Trondelag County (HUNT-2). All residents of this Norwegian county aged 19 years or older were asked to fill out a detailed questionnaire. Of these participants, 66% (61,349) completed this self-report questionnaire. Study subjects were also asked to complete a 14-item survey covering symptoms of anxiety and depression during the last 2 weeks.

Using a cutoff score to screen for depression and anxiety according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the researchers organized the respondents into 4 groups: case-level anxiety only, case-level depression only, case-level comorbid anxiety and depression, and a reference group scoring below case levels on both scales.

Patient reports provided information on smoking habits, level of physical activity, alcohol use, educational level, and socioeconomic status. Researchers used patient-reported physical health data that included asthma, angina, cancer, diabetes, and hypertension to create an index of somatic symptoms weighted for their associations with mortality. They also collected data on body mass index, blood pressure, and cholesterol levels.

The National Mortality Registry provided statistics on deaths from the date of screening to December 2000, which represented a mean follow-up of 4.4 years. During that time, there were 2309 deaths among the 61,349 residents.

The study found that after adjusting for age and sex, depression was strongly associated with mortality with an odds ratio of 1.68, whereas anxiety had an odds ratio of 1.19, and comorbid anxiety and depression had an odds ratio of 1.44.

Depression remained a risk factor for mortality even after controlling for somatic symptoms and diagnoses. These factors accounted for less than a quarter of the association between depression and mortality.

Even after adjusting for alcohol problems, educational level, socioeconomic status, body mass index, blood pressure, and cholesterol level, a substantial proportion of the association between depression and mortality remained unexplained.

Comparison Holds Up

To illustrate the strength of the association between depression and mortality, the researchers compared it to that of smoking, a well-known risk factor for overall mortality.

After adjusting for age and sex, the association between depression and mortality, (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.35 – 1.72), was almost the same as that of current smoking (HR, 1.59; 95% CI, 1.44 – 1.75).

Fully adjusted, the difference was somewhat stronger in smoking (HR, 1.42) compared with depression (HR, 1.27).

"Smoking and mortality seems to be similar to depression and mortality," said Dr. Mykletun. "Both of them, of course, are attenuated when we take adjusting factors into account, but the striking thing is that this comparison seems hold up regardless of the level of adjustment."

There were no sex differences in the association between depression and mortality.

Taking some potential confounding factors into account may "overadjust" for the association between depression and mortality, as these factors may be a result of depression rather than a cause of it, said Dr. Mykletun.

A "conservative" estimate is that depression can account for a 40% increase in the risk of mortality, whereas a less conservative estimate that adjusts for more of these factors would be closer to a 60% increase, he said

U-Shape Curve for Anxiety

With respect to the association between anxiety and mortality, the researchers found a U-shaped curve with both high and low levels of anxiety symptoms linked to increased risk.

A possible explanation for some anxiety protecting against mortality is that it may make people less likely to indulge in risky behavior and also push them to seek proper healthcare, said Dr. Mykletun.

"For example, if you feel sudden chest pain and you're absolutely without anxiety, you may not seek any emergency attention for those symptoms, and that might be lethal," he said.

However, the finding that having few anxiety symptoms — no restlessness, no butterflies in the stomach, no feelings of worry that something bad is about to happen — increases the risk for mortality is somewhat surprising, he said.

Adjusted for physical health, the researchers found no association between case-level anxiety and mortality.

When adding anxiety to depression, the risk for mortality found with depression alone is reduced, a finding that is rather "novel," said Dr. Mykletun. A possible explanation for this is that anxiety and depression represent the ends of an axis expressing 2 different types of pathology, he said.

"Depression makes you passive and everything seems hopeless, whereas anxiety has the opposite behavioral response to stimuli — you're restless, you want to act immediately. These opposing responses might explain why anxiety on top of depression might be better than depression alone."

The study should serve as a reminder to physicians to consider somatic symptoms in their depressed patients, said Dr. Mykletun. "We already know that depression is undertreated, and there's increasing attention to undertreatment of somatic illness in those with depression. This study might be additional evidence to back up the conclusion that we should take depression more seriously."

Comparison With Smoking a "Terrific Metaphor"

Asked by Medscape Psychiatry to comment on the study findings, Peter Kramer, MD, from Brown University, Providence, Rhode Island, said the results are important in that the study was large and thorough.

Depression, he said, is a multisystem disease that involves changes not only in the brain but also in blood vessels, heart, and bones. "Of the major common mental illnesses, depression really stands out as looking like ordinary disease across a number of body systems."

Dr. Kramer said the comparison with smoking was "a terrific metaphor" in that it gives people "a sense of the size of the contribution" of depression to mortality. He was also intrigued by the U-shaped curve found with anxiety. "It looks like there's some optimal level of anxiety. If you're depressed and have no anxiety, that might be a very bad set-up because you're doing very badly physically and you're not worried enough to take measures."

The authors have disclosed no relevant financial relationships.

Br J Psychiatry. 2009;195:118–125.

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