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February 6, 2009 — Bipolar disorder appears to increase the risk for premature death due to medical illness, including cardiovascular and cerebrovascular disease, endocrine disorders, and chronic obstructive pulmonary disease (COPD).

The first systematic review to examine mortality data in bipolar disorder shows that affected individuals have between a 1.5- and 2-fold increased risk for premature death due to these common medical conditions.
"It appears bipolar disorder is as big a risk factor for premature mortality as smoking. This is a major finding and drives home the message that as psychiatrists we should be regularly monitoring the physical status of our patients with chronic mental illness," principal investigator Wayne Katon, MD, from the University of Washington School of Medicine, in Seattle, said.

With first author Babak Roshanaei-Moghaddam, MD, the study is published in the February issue of Psychiatric Services.

Striking Findings
According to Dr. Katon, several studies have shown a link between major depression and an increased risk for early mortality due to general medical illnesses. Recent evidence from literature reviews in schizophrenia reveals similar results.

In the past, excess deaths associated with bipolar illness were attributed to unnatural causes, such as suicide, homicide, and accidents. However, a growing body of literature suggests this may account for only a portion of premature mortality in these individuals.
The investigators reviewed 17 studies involving more than 331,000 patients with bipolar disorder, affective psychosis, affective disorder requiring inpatient psychiatric care or treatment with lithium, or schizoaffective disorder.

Compared with age- and sex-matched control samples without mental illness from the general population, mortality ratios for death from natural causes and from specific general medical conditions such as heart disease, stroke, diabetes, and COPD were significantly higher.
The investigators point out this finding was particularly striking in larger studies of more than 2500 patients with bipolar disorder.

Vicious Cycle

While the mechanism is not entirely clear, Dr. Katon said research by his group investigating the link between major depression and conditions such as heart disease, osteoarthritis, and diabetes suggests there may be a bidirectional adverse interaction between chronic mental illness and medical illness.
Having a major mental illness such as bipolar disorder increases the likelihood of developing physical illness through a variety of factors, including poor diet, smoking, lack of exercise, substance abuse, social deprivation, and a lack of medical care, among others.

In addition, he said, the chronic stress inherent in having a major medical illness can affect the hypothalamic pituitary adrenal axis, increasing cortisol levels and leading to heightened activity of the sympathetic nervous system, possibly leading to earlier development of medical illness.

Once patients with a mental illness contract a medical illness, it is often a greater challenge for them to manage their condition. With diseases like diabetes, which requires a lot of self-care, poor management can lead to more complications, which in turn can feed back and exacerbate the mental-health condition.
"It really can turn into a vicious cycle," said Dr. Katon.

Role of Atypical Antipsychotics
Another potential contributing factor to physical illness and premature mortality in patients with bipolar disorder has been the introduction of second-generation, or atypical, antipsychotics and mood stabilizers, which are now in widespread use.

While these agents have fewer adverse effects, including extrapyramidal symptoms, than their first-generation counterparts, they are associated with obesity and metabolic abnormalities that may increase the risk for morbidity and mortality resulting from diabetes and cardiovascular disease, the researchers note.
"So what we've seen in recent years is a beginning of the understanding in the field that mood stabilizers and atypical antipsychotics, although effective in treating mental illness, are bringing new problems to bear.
"This has really gotten people's attention and raised awareness in a way I've never seen before — that, as psychiatrists, we need to pay closer attention to our patients' physical health. There's not much point in effectively treating them for their mental-health problems only to watch them die prematurely from their medical diseases," said Dr. Katon.

Attempts to reduce rates of premature mortality in mentally ill patients are under way and include increased training among psychiatry residents about common medical illnesses and the importance of addressing risk factors.

New Models of Care Needed
In addition, he said, new models of care that marry primary-care health services with community mental-health care are currently being developed and tested.

"Psychiatrists are now on the staff of a growing number of medical-specialty clinics, such as centers for diabetes, heart disease, and cancer, and at primary-care centers such as family-medicine practices," Dr. Katon said.

"Mental-health professionals are working side by side with providers who treat medical illnesses. New approaches to healthcare and wellness programs are being tested at a number of places to find effective models for preventing premature deaths associated with bipolar disorder and other mental illnesses," he added.


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