Psychiatric comorbidity increases the risk of premature mortality in epilepsy

shutterstock_93305014

There is a back to school feeling in the air in the Woodland this week, and so this comes to you with the help of my shiny new yellow pencil case.

Epilepsy affects around 70 million people around the world and premature mortality is substantial with almost half of epilepsy-related deaths occuring in those younger than 55 years. The contribution of psychiatric comorbidity is not clear and although suicide has been associated with epilepsy deaths, whether this is an independent association has not been clarified.

In July of this year Fazel and colleagues published their Swedish total population cohort study in the Lancet. In this 41-year population study of 69,995 individuals with epilepsy, they aimed to investigate prevalence and risks of premature mortality from external causes such as suicide, accidents, and assaults in people with epilepsy with and without psychiatric comorbidity.

Methods

The Swedish total population cohort provides researchers with the opportunity to conduct studies such as this one

The Swedish total population cohort provides researchers with the opportunity to conduct studies such as this one

Using the nationwide population registers in Sweden they studied all individuals born in Sweden between 1954 and 2009 with inpatient and outpatient diagnoses of epilepsy (n=69,995) for risks and causes of premature mortality. Patients were compared with age-matched and sex-matched general population controls (n=660,869) and unaffected siblings (n=81,396).

The aims of the study were to address two specific issues;

  1. Whether epilepsy is independently associated with external causes of death
  2. To investigate the association of epilepsy with premature mortality in patients with and without comorbid psychiatric disorders

Results

adjusted odds of all-cause mortality in patients with epilepsy was 11 compared with both general population and unaffected sibling controls

  • 6155 (8.8%) patients with epilepsy died before the end of the follow-up period compared with 4892 (0.7%) controls
  • Rates of psychiatric comorbidity were 18.0% before diagnosis of epilepsy and 22.7% after diagnosis
  • 16% of all epilepsy deaths were from external causes, which was the largest category of deaths that was not clearly related to underlying disease processes (such as brain tumours and infections).

Odds ratios for death (with 95% CI) compared with general population:

Psychiatric comorbidity associated with marked increased risk of mortality

Psychiatric comorbidity was associated with a marked increased risk of mortality

  • Suicide 3.7 (3.3–4.2)
  • Vehicle accidents 1.4 (1.1–1.8)
  • Drug poisoning 5.1 (3.9–6.5)
  • Falls 8.5 (5.3–13.7)
  • Drowning 7.7 (4.7–12.7)
  • Assault 2.8 (1.6–4.8)

Comparing with unaffected siblings all risk estimates remained raised.

Of those who died from external causes;

  • 75.2% had comorbid psychiatric disorders, with strong associations in individuals with co-occurring depression (13.0, 10.3—16.6) and substance misuse (22.4, 18.3—27.3), compared with patients with no epilepsy and no psychiatric comorbidity.
  • Epilepsy and comorbid depression had an odds ratio for suicide of 23
  • Epilepsy and comorbid substance misuse had an odds ratio for suicide of 21
  • The corresponding odds of suicide in general population controls with depression but without epilepsy was 10

Conclusions

Risks for external causes of death, and potential treatments to mitigate these risks, need to be considered in patients with epilepsy. The importance of identifying, monitoring, and treating psychiatric comorbidity, is reinforced by these results and clinical epilepsy services could review their liaison with psychiatric and addiction services. Whilst bearing in mind that although the relative risks were high, absolute rates of premature mortality from external causes were 1.4%, and any changes to clinical practice need to consider how to identify high-risk populations with low false positive rates

Any psychiatric comorbidity should be looked for in patients with epilepsy

Any psychiatric comorbidity should be looked for in patients with epilepsy

The results show high rates of premature mortality in epilepsy, and highlight the substantial contribution of psychiatric comorbidity to this mortality. The findings potentially contribute to the clinical management of epilepsy for neurology, psychiatry, and primary care services by presenting information on associations with treatable psychiatric disorders.

The findings appear to be robust; the study benefited from a large sample size, various sensitivity analyses, and examined familial confounding. To the researchers knowledge, this is the first time that unaffected sibling controls have been used to assess mortality in epilepsy.

Reducing premature mortality from external causes of death should be a priority in epilepsy management. The ability of health services to prevent such deaths now requires further review.

Signing off today with the help of Elbow…

Links

Fazel S, Wolf A, Långström N, Newton CR, Lichtenstein P. Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study. Lancet. 2013 Jul 19. pii: S0140-6736(13)60899-5. doi: 10.1016/S0140-6736(13)60899-5. [Epub ahead of print] [PubMed abstract]