Bipolar disorder linked to heightened risk of early death from external causes

People with bipolar disorder—characterized by extreme mood swings—are six times more likely to die before their time from external causes, such as accidents, violence, and suicide, than those without the condition, finds research published in the open access journal BMJ Mental Health.

And they are twice as likely to die from somatic (physical) causes, with alcohol a major contributing factor, the findings show.

A heightened risk of an early death from any cause has been consistently reported in those with bipolar disorder from several countries. But it’s not clear if there are particular drivers, or to what extent somatic illness—physical disease—contributes to this risk.

The Finnish researchers therefore drew on nationwide medical and social insurance registers to identify and track the health of all 15–64-year-olds with bipolar disorder between 2004 and 2018.

They calculated the ratio of the number of deaths observed over a given period (around eight years of monitoring) among those diagnosed with bipolar disorder to the number expected in the Finnish general population—the standard mortality ratio (SMR)—to find the excess deaths directly attributable to the condition.

They tracked the outcomes of 47,018 people with bipolar disorder who were 38, on average, at the start of the monitoring period. More than half (57%) were women.

In all, 3,300 (7%) of them died during the monitoring period compared with 141,536 people in the general population, equating to a six-fold higher risk of death from external causes and a two-fold higher risk of death from somatic causes.

Their average age at death was 50; almost two thirds (65%; 2,137) of these deaths were among men. The cause of death was somatic in 61% (2,027) and external in 39% (1,273).

Among the 2,027 somatic illness deaths, alcohol caused the most at 29% (595); followed by heart disease and stroke (27%, 552); cancer (22%, 442); respiratory disease (4%,78); diabetes (2%,41); and behavioral disorders associated with other substance misuse (1%, 23). The remaining 15% (296) comprised various other causes.

Of the 595 alcohol-related deaths, liver disease accounted for nearly half (48%), followed by accidental alcohol poisoning (28%), and alcohol dependence (10%).

Among the external cause deaths, most were due to suicide (58%, 740), nearly half of which (48%) were due to overdose with prescribed mental health meds, including those used to treat bipolar disorder.

Overall, nearly two thirds (64%, 2,104) of the deaths from any cause were excess deaths—higher than would be expected for comparable age and sex and directly attributable to bipolar disorder.

Of those due to somatic causes, 51% (1,043) were excess deaths compared with 83% (1,061) of those due to external causes.

Most of the excess deaths from somatic illness were either due to alcohol-related causes (40%)—a rate that is three times higher than that of the general population—cardiovascular disease (26%), or cancer (10%).

Of the excess deaths from external causes, 61% (651) were due to suicide, a proportion that is around eight times higher than that of the general population.

Excess deaths from external causes were substantial in all age groups, but while most of the excess among 15–44 year olds was from external causes, external and somatic causes contributed in nearly equal numbers to this among 45–64 year olds.

The researchers excluded those diagnosed with schizophrenia and other psychotic illnesses, which may have resulted in an underestimation of the excess deaths due to bipolar disorder, they acknowledge. A history of persistent symptoms of psychosis, delusions and hallucinations is known to be associated with a greatly increased risk of death, they explain.

Given that external causes seem to have a greater role than physical illness in excess deaths among those with bipolar disorder, the current therapeutic focus on preventing physical illness to reduce this excess should be reconsidered, argue the researchers.

“A balanced consideration between therapeutic response, potential serious long term somatic side effects of different medicines, and risk of cause-specific premature mortality is needed, especially in younger persons,” they write.

“Targeting preventive interventions for substance abuse will likely reduce the mortality gap both due to external causes and somatic causes. Suicide prevention remains a priority, and better awareness of the risk of overdose and other poisonings is warranted,” they add.

More information:
Cause-specific excess mortality after first diagnosis of bipolar disorder: population-based cohort study, BMJ Mental Health (2023). DOI: 10.1136/bmjment-2023-300700