ATLANTA— Patients with bipolar and unipolar disorders have increased mortality compared with the general population, and patients’ age at onset is an important indicator of risk, according to a study conducted in Sweden. Urban Ösby, MD, PhD, reported the results at the 158th Annual Meeting of the American Psychiatric Association. The study included all patients with a hospital diagnosis of bipolar or unipolar disorder from 1973 through 1995 who were identified in the Swedish psychiatric patient register. Bipolar disorder was defined as patients with a manic state.

Dr. Ösby, of the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, and colleagues identified 6,578 men and 8,808 women with bipolar disorder, as well as 15,829 men and 23,353 women with unipolar disorder. Standardized mortality ratios (SMRs) as well as the number of excess deaths were calculated for bipolar and unipolar disorder patients. The age- and gender-specific mortality rates for the total population were used to estimate the expected number of deaths. SMRs and number of excess deaths were calculated for all specific causes of death and for all natural and all unnatural causes.

The leading causes of death in both men and women with bipolar disorder were cardiovascular difficulties and suicide, Dr. Ösby reported; 550 men died of cardiovascular disorders, 345 died as a result of suicide, 193 died from cancer, and 111 died of respiratory problems. Overall, 1,716 men with bipolar disorder died; 1,185 deaths were from natural causes and 531 were from unnatural causes. Of the 1,747 women with bipolar disorder, 523 died of cardiovascular difficulties, 327 died as a result of suicide, 282 died of cancer, 127 died of cerebrovascular causes, and 113 died of respiratory problems. There were 1,280 deaths due to natural causes and 467 due to unnatural causes.

In men and women with unipolar disorder, cardiovascular disorders and suicide were also the leading causes of death. Of the 4,119 men, 1,319 died of cardiovascular complications, 1,052 died as a result of suicide, and 547 died of cancer. A total of 2,747 men died of natural causes and 1,372 died of unnatural causes, he noted. Of the 4,902 women with unipolar disorder, 1,428 died of cardiovascular causes, 993 died as a result of suicide, and 830 died from cancer. Overall, 3,615 died of natural causes, and 1,287 died of unnatural causes.

To determine SMRs, the number of observed deaths was divided by the number of expected deaths. The highest SMRs in both men and women with bipolar and unipolar disorders were for suicides and violent deaths. In bipolar disorder, SMRs for suicide were 15.0 for men and 22.4 for women, and SMRs for undetermined violent deaths, likely to be from suicide, although not classified as such, were 10.3 and 14.2, respectively. “These numbers are much higher than in most other studies, and are likely to be explained by the inclusion of all patients from the first diagnosis, since suicide mortality was shown to be most increased in the first years after the first diagnosis, and thus studies starting from cross-sectional patient samples will misrepresent the part of the illness course with the most increased suicide mortality,” Dr. Ösby remarked. In unipolar disorder, SMRs for suicide were 20.9 for men and 27.0 for women, and SMRs for undetermined violent deaths were 8.3 and 11.9, respectively. “These numbers are in line with findings from previous studies. Interestingly, mortality from natural causes of death were also increased. SMRs for cardiovascular mortality in bipolar disorder were 1.9 for men and 2.6 for women, and those for all natural causes of death were 1.9 for men and 2.1 for women. In unipolar disorder, SMRs were 1.5 for men and 1.7 for women for cardiovascular mortality, and 1.5 and 1.6, respectively, for mortality from all natural causes. Considering that suicide is an uncommon cause of death in the population, while cardiovascular complications are the most frequent, the increased SMRs for cardiovascular and natural causes in bipolar and unipolar disorder represent as large numbers of excess deaths as the highly increased SMRs for suicide.”

When evaluating the methods of suicide among patients, the investigators found that men with bipolar disorder more often chose jumping or cutting as their method of suicide, whereas women with bipolar disorder more often chose jumping or shooting. Men with unipolar disorder more often chose drowning or hanging, while women with unipolar disorder more often chose shooting or hanging. “Additionally, having a first-degree family member who has committed suicide leads to a double suicide risk for bipolar patients,” Dr. Ösby said.

NUMBER OF EXCESS DEATHS

The investigators found that in men with bipolar disorder, there were 1,030 excess deaths due to all causes. Of these, 266 were due to cardiovascular causes and 561 were due to all natural causes, while 322 excess deaths were due to suicide and 471 were due to all unnatural causes. In women with bipolar disorder, there were 2,129 excess deaths due to all causes. There were 591 excess deaths due to cardiovascular causes and 1,229 excess deaths due to all natural causes. There were 634 excess deaths due to suicide and 900 excess deaths due to all unnatural causes, Dr. Ösby reported. “Thus, although suicide was the specific cause of death with most excess deaths, in total for bipolar disorder patients there were more excess deaths from natural than from unnatural causes.”

In men with unipolar disorder, there were 448 excess deaths due to cardiovascular causes and 865 excess deaths due to all natural causes. There were 1,002 excess deaths due to suicide and 1,232 excess deaths due to all unnatural causes. Overall, there were 2,097 excess deaths due to all causes for men with unipolar disorder. In women with unipolar disorder, there were 2,487 excess deaths due to all causes; 608 were due to cardiovascular causes and 1,305 were due to all natural causes, while 956 excess deaths were due to suicide and 1,182 excess deaths were due to all unnatural causes. “Even in unipolar disorder, for women there were more excess deaths from natural than from unnatural causes, and for men there were more excess deaths from natural causes than from suicide,” Dr. Ösby said.

FINAL ANALYSIS

“In order to prevent the excess mortality both in bipolar and unipolar disorder, focus should be on reducing the number of excess deaths rather than on reducing SMRs,” Dr. Ösby said. “To reduce suicide rates, we should focus on younger patients in the first phase of illness, since suicide rate correlates to the duration of the illness, with the greatest number of suicides occurring soon after diagnosis,” he added. “However, the large number of excess deaths from natural causes, mainly cardiovascular, necessitates a second preventive long-term focus in order to improve the long-term course of affective disorders in these regards, which have not received proper attention so far.”

—Michelle Stephenson

Suggested Reading
Ösby U, Brandt L, Correia N, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58:844-850.

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