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Bipolar disorder patients die prematurely from a wide range of causes, from heart disease to the flu, a Swedish population study showed.

But that grim trend might be eased by increased access to primary care providers, Casey Crump, MD, PhD, of Stanford University in Stanford, Calif., and colleagues reported online in JAMA Psychiatry.

All-cause mortality was 2.3-fold elevated among women and 2.0-fold higher among men with the psychiatric condition compared with the rest of Sweden after adjusting for other factors, they wrote.

Moreover, chronic disease mortality was more weakly linked to bipolar disorder when diagnosed before death than at the time of death.

"Timely medical diagnosis appeared to improve chronic disease mortality among bipolar disorder patients to approach that of the general population," they wrote. "More effective provision of primary, preventive medical care is needed to reduce early mortality among persons with bipolar disorder."

Prior studies have also suggested elevated premature mortality in bipolar disorder, similar to that in schizophrenia and other neurotic disorders, but largely using hospital-based samples that might include only the more severe cases, the researchers noted.

They analyzed national inpatient and outpatient registries from 2003 through 2009 for all 6.6 million adults ages 20 and older living in Sweden for at least 2 years, among whom 6,618 had bipolar disorder.

Women and men with bipolar disorder died 9.0 and 8.5 years younger on average than the rest of the population, with crude mortality rates of 28.5 and 30.3 per 1,000 person-years versus 14.5 and 14.1 per 1,000, respectively.

Suicide was substantially more common than in the general population, accounting for 5% of deaths among women and 10% among men with bipolar versus 1% and 2%.

Unintentional injuries were also a 10-fold higher risk for women and eight-fold higher risk among men with bipolar disorder after adjustment for age and other factors.

But "this life expectancy difference was not fully explained by unnatural deaths," the researchers pointed out.

Looking just at death from natural causes, the bipolar patients died roughly 7 years earlier than those without the disorder.

After adjusting for age and sociodemographic factors, bipolar disorder was associated with significantly elevated mortality risk from the following comorbidities:

• Influenza or pneumonia, elevated 3.7-fold among women and 4.4-fold among men
• Diabetes, elevated 3.6-fold among women and 2.6-fold among men
• Chronic obstructive pulmonary disease (COPD), elevated 2.9-fold among women and 2.6-fold among men
• Stroke, elevated 2.6-fold among women but not men
• Cancer, elevated 40% among women but not men
• Colon cancer, elevated 2.1-fold among women, albeit based on only 13 deaths

Further adjustment for substance use disorders modestly attenuated most of these risk estimates without altering their statistical significance; additional adjustment for smoking (using previously reported smoking rates rather than individual data) cut a number of the risk estimates by 15%, again without eliminating statistical significance.

The adjusted hazard ratio for death from chronic diseases -- ischemic heart disease, diabetes, COPD, or cancer -- with bipolar disorder was weaker with diagnosis of the chronic conditions more than 30 days prior to death than without a prior diagnosis (1.40 versus 2.38, P=0.01 for interaction).

All-cause mortality risk wasn't uniform across bipolar treatment groups.

After adjustment for sociodemographics and substance use disorders, risks were 20% to 30% lower with any use of aripiprazole (Abilify), quetiapine (Seroquel), or lamotrigine (Lamictal) and 20% to 40% higher with sole use of olanzapine (Zyprexa) and sole or any use of valproic acid, risperidone (Risperdal), or carbamazepine (Tegretol) versus lithium alone.

No bipolar disorder treatment was associated with 60% higher all-cause mortality, though, and double the risk of suicide.

"These findings should be interpreted with caution because of possible confounding by disease severity or other unmeasured factors and because few patients received monotherapy and precision was limited for specific medications," the group warned.

Other lifestyle factors, treatment effects, and psychiatric comorbidities need further study as potential mediators, they suggested.

Limitations included lack of data on physical activity and obesity as well as potential incomplete ascertainment of substance abuse and mild cases of bipolar disorder.

Moreover, the disparity in mortality may be even larger in other countries without universal health care, the researchers noted.

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