People with bipolar disorder are more likely to die at a younger age compared with the general population (Crump et al 2013; Hoang et al 2013). This is often due to high rates of suicide and violent crime, which I blogged about last year, but may also be attributed to a heightened risk for physical health problems.

In 2013, Rethink published a report (PDF) outlining a number of common factors which can lead to medical illnesses in this population such as smoking, side effects from antipsychotic medication, as well as poor physical health monitoring and stigma.

Hayes and colleagues (2015) conducted a systematic review and meta-analysis of large observational studies to estimate the mortality rate of people with bipolar disorder compared with the general population. They looked at a range of different reasons for mortality which included unnatural causes, such as suicide and violent crime, as well as natural causes, such as circulatory and respiratory problems.

Methods

The authors looked for eligible articles by searching three electronic databases, scanning reference lists of included studies and tracking citations using the Cochrane Database of Systematic Reviews and Google Scholar.

Studies were included if they reported data on deaths of people with a diagnosis of bipolar disorder (any criteria were accepted), due to any reason (all-cause mortality) or deaths due to specific reasons (cause-specific mortality) including:

• Natural deaths
• Unnatural deaths
• Suicide
• Other violent deaths
• Infection
• Neoplasm
• Respiratory
• Circulatory system disease

Studies were excluded if they had fewer than 50 participants or were not standardised by age.

Standardised mortality ratios (SMRs) with their 95% confidence intervals were used to calculate the ratio of participants with bipolar disorder who died for each reason compared with the general population. SMRs greater than 1 indicate increased mortality in people with bipolar disorder compared with the general population, whereas those smaller than 1 indicate decreased mortality in this population.

Heterogeneity within each meta-analysis was assessed using the I² index and chi-square test. Additionally a number of meta-regressions were carried out for all-cause mortality controlling for: decade of publication, cohort size, geographical region, mid-decade of cohort data collection and population type (inpatient or community based). Subgroup analyses where also performed for geographical region of study, patient population type and decade of the middle year of patient observation.

Results

In total, 31 studies of 305,859 people with bipolar disorder met the inclusion criteria. Studies were mainly inpatient cohorts (64%) and a large proportion were conducted in Scandinavian countries (45%).

All-cause mortality

The SMR for all-cause mortality was 2.05 (95% CI 1.98 to 2.23), ranging from 1.24 (95% CI 0.83 to 1.17) to 4.65 (95% CI 1.27 to 11.91). Heterogeneity between studies was significant and high (p < 0.001, I² =96.2%).

Cause-specific mortality

SMRs indicated increased rates of death for people with bipolar disorder for all cause-specific mortality categories. Estimates were highest for death due to suicide (SMR=14.44) and unnatural causes (SMR=7.42). As for all-cause mortality, heterogeneity was significant and high for most categories except for infection and neoplasm which were relatively homogenous.

Cause-specific mortality	Summary SMR (95% CI)
Natural	1.64 (1.47 to 1.83)
Unnatural	7.42 (6.43to 8.55)
Suicide	14.44 (12.43to 16.78)
Other violent	3.68 (2.77to 4.90)
Circulatory	1.73 (1.54to 1.94)
Respiratory	2.92 (2.00to 4.23)
Infection	2.25 (1.70to 3.00)
Neoplasm	1.14 (1.10to 1.21)

Meta-regression and sub-group analyses

Meta-regression analyses revealed that none of the following variables could account for the heterogeneity in findings: decade of publication, cohort size, geographical region, mid-decade of cohort data collection or population type. Subgroup analyses also did not find any effect on heterogeneity when stratifying for geographical region, population type and mid-decade of study.

Conclusions

The authors concluded that:

This meta-analysis highlights differential mortality in patients with bipolar disorder and the general population. Similarly to schizophrenia, patients with bipolar disorder have over twice the all-cause mortality. Mortality from all physical conditions and unnatural causes is elevated. Variation in all-cause mortality is considerable across time and place. There is no evidence that all-cause mortality for patients with bipolar disorder has improved over time relative to the general population.

Strengths and limitations

The authors carried out a thorough search strategy using multiple databases and tracking citations from reference lists of included studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) proposal for reporting were also followed. However, despite being an item in both reporting checklists, the authors did not carry out an assessment of study quality, which may have played a role in the high levels of heterogeneity found.

Another limitation in this review is the fact that included studies only adjusted SMRs for age and gender. It therefore was not possible to assess whether other factors may have accounted for the increased rate of deaths or heterogeneity in findings. For example, people with a serious mental illness are more likely to smoke which may have had a significant impact on deaths due to respiratory problems.

Summary

Overall this review provides evidence that people with bipolar disorder have increased mortality rates compared with the general population.

For all-cause mortality, there was a two-fold increase, whereas for suicide the SMR was as high as 14, which reflects previous results from large cohort studies. Although there was considerable heterogeneity in the summary estimate, all studies showed an increased risk for all-cause mortality of which only 4 out of 31 showed confidence intervals which crossed the line of no effect. These studies were all relatively small (74-440 participants) which explains the large confidence intervals. This finding indicates that we can be fairly certain that a true increased risk exists, although the precise estimate is still uncertain.

An interesting finding was that when controlling for year of publication, there was no effect on estimates indicating no change in mortality ratios from 60 years ago with those completed recently. This highlights the need for improvements in physical and mental health monitoring, smoking cessation programmes and the provision of clear information about side effects of medication.

If you need help

If you need help and support now and you live in the UK or the Republic of Ireland, please call the Samaritans on 116 123.

If you live elsewhere, we recommend finding a local Crisis Centre on the IASP website.

We also highly recommend that you visit the Connecting with People: Staying Safe resource.

Links

Hayes JF, Miles J, Walters K, King M, Osborn DP. A systematic review and meta-analysis of premature mortality in bipolar affective disorder. Acta Psychiatr Scand. 2015 Jun;131(6):417-25 [PubMed abstract]

Crump C, Sundquist K, Winkleby MA, Sundquist J. Comorbidities and mortality in bipolar disorder: a Swedish national cohort study. JAMA Psychiatry. 2013;70:931-9. [PubMed abstract]

Hoang U, Goldacre MJ, Stewart R. Avoidable mortality in people with schizophrenia or bipolar disorder in England. Acta Psychiatr Scand. 2013;127:195-201 [PubMed abstract]

Lethal discrimination (PDF). Rethink Mental Illness, September 2013.

http://www.prisma-statement.org/

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008-12.