Bipolar disorder strongly tied to premature death

Women and men with bipolar disorder were more likely to die prematurely than were those without bipolar disorder, according to results from a Swedish national cohort study involving nearly 6.6 million adults.

After adjustment for age, marital status, educational level, employment status, and income, all-cause mortality among the 6,618 adults with bipolar disorder in the cohort was increased twofold for both women (adjusted hazard ratio, 2.34) and men (AHR, 2.03), who died an average of 9.0 and 8.5 years earlier, respectively, did than those without bipolar disorder, according to Dr. Casey Crump of Stanford (Calif.) University, and his colleagues.

Those with bipolar disorder died prematurely from various causes, including cardiovascular disease, diabetes, chronic obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional injuries, and suicide. Among women, stroke and cancer (particularly colon cancer) were also among the causes of premature death. Suicide was a particular risk for both women and men, who had 10-fold and 8-fold increases in risk, respectively (AHRs, 10.37 and 8.09), but the life expectancy differences were not fully explained by unnatural deaths, the investigators reported July 17 online in JAMA Psychiatry.

The most significant causes of death were influenza or pneumonia (3.7- and 4.4-fold increased risk for women and men, respectively), diabetes (3.6- and 2.6-fold increased risk, respectively), and COPD (2.9- and 2.6-fold increased risk).

In a separate model, the potential mediating effect of substance use disorders also was evaluated, and the effect was found to be modest, the investigators noted.

The associations between the various conditions and premature death were weakest for chronic diseases in those with a prior diagnosis, compared with those without a prior diagnosis (AHRs, 1.40 vs. 2.38), suggesting that earlier medical diagnosis and treatment might attenuate the increased mortality risk among affected individuals, they said (JAMA Psychiatry 2013 July 17 [doi: 10.1001/jamapsychiatry.2013.1394]).

"More complete provision of primary, preventive medical care among bipolar disorder patients is needed to reduce early mortality in this vulnerable population," they said, noting that multiple underlying mechanisms, including lifestyle factors, pathophysiologic mechanisms, genetic factors, and certain treatments for bipolar disorder, contribute to the disparities.

"The current study found evidence of modestly increased mortality among bipolar disorder patients who used carbamazepine, risperidone, or valproic acid or who solely used olanzapine, whereas users of aripiprazole, quetiapine, or lamotrigine had modestly reduced mortality compared with those who solely used lithium," they said.

However, consistent with prior research, those who used none of these medications had even higher rates of all-cause mortality – and twice the suicide risk – of those who used medication.

Study participants were 3,918 women and 2,700 men aged 20 years or older who lived in Sweden for at least 2 years as of Jan. 1, 2003. They were followed up to assess for physical comorbidities and mortality for 7 years. Bipolar disorder in the cohort was identified by any diagnosis during the preceding 2 years, and by the use of specific medications commonly used for bipolar disorder maintenance treatment.

The findings of this study, which is among the first to examine the association between bipolar disorder and mortality using complete diagnoses for a national population, adds to the increasing knowledge about factors that contribute to premature mortality in patients with bipolar disorder, but it is unclear to what extent the findings can be generalized to other health care systems, the investigators said.

"The substantial health disparities we found between bipolar disorder patients and the rest of the Swedish population may be even larger in other countries without universal health care," they noted.

This study was supported by a grant from the National Institute on Drug Abuse and an Agreement on Medical Training and Research (Lund, Sweden) project grant. The authors reported having no disclosures.

Women and men with bipolar disorder were more likely to die prematurely than were those without bipolar disorder, according to results from a Swedish national cohort study involving nearly 6.6 million adults.

After adjustment for age, marital status, educational level, employment status, and income, all-cause mortality among the 6,618 adults with bipolar disorder in the cohort was increased twofold for both women (adjusted hazard ratio, 2.34) and men (AHR, 2.03), who died an average of 9.0 and 8.5 years earlier, respectively, did than those without bipolar disorder, according to Dr. Casey Crump of Stanford (Calif.) University, and his colleagues.

Those with bipolar disorder died prematurely from various causes, including cardiovascular disease, diabetes, chronic obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional injuries, and suicide. Among women, stroke and cancer (particularly colon cancer) were also among the causes of premature death. Suicide was a particular risk for both women and men, who had 10-fold and 8-fold increases in risk, respectively (AHRs, 10.37 and 8.09), but the life expectancy differences were not fully explained by unnatural deaths, the investigators reported July 17 online in JAMA Psychiatry.

The most significant causes of death were influenza or pneumonia (3.7- and 4.4-fold increased risk for women and men, respectively), diabetes (3.6- and 2.6-fold increased risk, respectively), and COPD (2.9- and 2.6-fold increased risk).

In a separate model, the potential mediating effect of substance use disorders also was evaluated, and the effect was found to be modest, the investigators noted.

The associations between the various conditions and premature death were weakest for chronic diseases in those with a prior diagnosis, compared with those without a prior diagnosis (AHRs, 1.40 vs. 2.38), suggesting that earlier medical diagnosis and treatment might attenuate the increased mortality risk among affected individuals, they said (JAMA Psychiatry 2013 July 17 [doi: 10.1001/jamapsychiatry.2013.1394]).

"More complete provision of primary, preventive medical care among bipolar disorder patients is needed to reduce early mortality in this vulnerable population," they said, noting that multiple underlying mechanisms, including lifestyle factors, pathophysiologic mechanisms, genetic factors, and certain treatments for bipolar disorder, contribute to the disparities.

"The current study found evidence of modestly increased mortality among bipolar disorder patients who used carbamazepine, risperidone, or valproic acid or who solely used olanzapine, whereas users of aripiprazole, quetiapine, or lamotrigine had modestly reduced mortality compared with those who solely used lithium," they said.

However, consistent with prior research, those who used none of these medications had even higher rates of all-cause mortality – and twice the suicide risk – of those who used medication.

Study participants were 3,918 women and 2,700 men aged 20 years or older who lived in Sweden for at least 2 years as of Jan. 1, 2003. They were followed up to assess for physical comorbidities and mortality for 7 years. Bipolar disorder in the cohort was identified by any diagnosis during the preceding 2 years, and by the use of specific medications commonly used for bipolar disorder maintenance treatment.

The findings of this study, which is among the first to examine the association between bipolar disorder and mortality using complete diagnoses for a national population, adds to the increasing knowledge about factors that contribute to premature mortality in patients with bipolar disorder, but it is unclear to what extent the findings can be generalized to other health care systems, the investigators said.

"The substantial health disparities we found between bipolar disorder patients and the rest of the Swedish population may be even larger in other countries without universal health care," they noted.

This study was supported by a grant from the National Institute on Drug Abuse and an Agreement on Medical Training and Research (Lund, Sweden) project grant. The authors reported having no disclosures.

Women and men with bipolar disorder were more likely to die prematurely than were those without bipolar disorder, according to results from a Swedish national cohort study involving nearly 6.6 million adults.

After adjustment for age, marital status, educational level, employment status, and income, all-cause mortality among the 6,618 adults with bipolar disorder in the cohort was increased twofold for both women (adjusted hazard ratio, 2.34) and men (AHR, 2.03), who died an average of 9.0 and 8.5 years earlier, respectively, did than those without bipolar disorder, according to Dr. Casey Crump of Stanford (Calif.) University, and his colleagues.

Those with bipolar disorder died prematurely from various causes, including cardiovascular disease, diabetes, chronic obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional injuries, and suicide. Among women, stroke and cancer (particularly colon cancer) were also among the causes of premature death. Suicide was a particular risk for both women and men, who had 10-fold and 8-fold increases in risk, respectively (AHRs, 10.37 and 8.09), but the life expectancy differences were not fully explained by unnatural deaths, the investigators reported July 17 online in JAMA Psychiatry.

The most significant causes of death were influenza or pneumonia (3.7- and 4.4-fold increased risk for women and men, respectively), diabetes (3.6- and 2.6-fold increased risk, respectively), and COPD (2.9- and 2.6-fold increased risk).

In a separate model, the potential mediating effect of substance use disorders also was evaluated, and the effect was found to be modest, the investigators noted.

The associations between the various conditions and premature death were weakest for chronic diseases in those with a prior diagnosis, compared with those without a prior diagnosis (AHRs, 1.40 vs. 2.38), suggesting that earlier medical diagnosis and treatment might attenuate the increased mortality risk among affected individuals, they said (JAMA Psychiatry 2013 July 17 [doi: 10.1001/jamapsychiatry.2013.1394]).

"More complete provision of primary, preventive medical care among bipolar disorder patients is needed to reduce early mortality in this vulnerable population," they said, noting that multiple underlying mechanisms, including lifestyle factors, pathophysiologic mechanisms, genetic factors, and certain treatments for bipolar disorder, contribute to the disparities.

"The current study found evidence of modestly increased mortality among bipolar disorder patients who used carbamazepine, risperidone, or valproic acid or who solely used olanzapine, whereas users of aripiprazole, quetiapine, or lamotrigine had modestly reduced mortality compared with those who solely used lithium," they said.

However, consistent with prior research, those who used none of these medications had even higher rates of all-cause mortality – and twice the suicide risk – of those who used medication.

Study participants were 3,918 women and 2,700 men aged 20 years or older who lived in Sweden for at least 2 years as of Jan. 1, 2003. They were followed up to assess for physical comorbidities and mortality for 7 years. Bipolar disorder in the cohort was identified by any diagnosis during the preceding 2 years, and by the use of specific medications commonly used for bipolar disorder maintenance treatment.

The findings of this study, which is among the first to examine the association between bipolar disorder and mortality using complete diagnoses for a national population, adds to the increasing knowledge about factors that contribute to premature mortality in patients with bipolar disorder, but it is unclear to what extent the findings can be generalized to other health care systems, the investigators said.

"The substantial health disparities we found between bipolar disorder patients and the rest of the Swedish population may be even larger in other countries without universal health care," they noted.

This study was supported by a grant from the National Institute on Drug Abuse and an Agreement on Medical Training and Research (Lund, Sweden) project grant. The authors reported having no disclosures.