This study aims to determine the contribution of comorbidly to excess PNES mortality.
Retrospective cohort study of tertiary epilepsy outpatients from St Vincent’s Hospital Melbourne, Australia with 8:1 comparison cohort, matched by age, sex and socioeconomic status (SES) to national administrative databases between 2007-2017. Privacy-preserving data-linkage was undertaken with the national prescription, National Death Index and National Coronial Information System. 45 comorbid disease classes were derived by applying an Australian validated RxRisk-V to all dispensed prescriptions. We fitted Cox proportional hazard models controlling for age, sex, SES, comorbidity, disease duration and number of concomitant antiseizure medications (ASM), as a marker of disease severity. We also performed a parallel forward-selection change in estimate strategy to explore which specific comorbidities contributed to the largest changes in the hazards ratio.
13,488 participants were followed for a median 3.2 years (IQR 2.4-4.0 years). 1,628 tertiary epilepsy outpatients. 1,384 patients with epilepsy, 176 PNES and 59 with both. 82% of epileptic seizures and 92% of typical PNES events were captured in an epilepsy monitoring unit. The age-sex-SES-adjusted hazards ratio (95% confidence interval) was elevated for epilepsy 4.74 (3.36, 6.68) and PNES 3.46 (1.38, 8.68) and remained elevated for epilepsy 3.21 (2.22, 4.63) but not PNES 2.15 (0.77, 6.04), after comorbidity adjustment. PNES had more pre-existing comorbidities (p=0.0007) with a three times greater median weighted Rx-RiskV score. Psychotic illness, opioid analgesia, malignancies and non-opioid analgesia had the greatest influence on PNES comorbid risk.
Higher comorbidity appears to explain the excess PNES mortality and may either represent a wider under recognised somatoform disorder or a psychological response to physical illness. Better understanding and management of the bidirectional relationship of these wider somatic treatments in PNES could potentially reduce the risk of death.

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