Serotonin reuptake inhibitors and mortality in epilepsy: A linked primary‐care cohort study

• Published in: Epilepsia (Copenhagen) 2017-11, Vol.58 (11), p.2002-2009
• Main Authors: Josephson, Colin B., Gonzalez‐Izquierdo, Arturo, Denaxas, Spiros, Fitzpatrick, Natalie K., Sajobi, Tolulope T., Engbers, Jordan D.T., Patten, Scott, Jette, Nathalie, Wiebe, Samuel
• Format: Article
• Language: English
• Subjects: Adult; All‐cause mortality; Antidepressants; Cohort analysis; Cohort Studies; Cohort study; Comorbidity; Electronic Health Records - trends; Electronic medical records; Epidemiology; Epilepsy; Epilepsy - drug therapy; Epilepsy - mortality; Female; Follow-Up Studies; Health risk assessment; Humans; Linked electronic medical records; Male; Mental depression; Middle Aged; Mortality; Mortality - trends; Primary Health Care - trends; Regression analysis; Seizures; Seizure‐specific mortality; Selective Serotonin Reuptake Inhibitors - adverse effects; Serotonin uptake inhibitors
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/epi.13904

Summary Objective Preliminary evidence suggests that serotonin reuptake inhibitor (SRI) use may increase postictal respiratory drive and prevent death. We sought to determine whether SRIs are associated with improved all‐cause and possible seizure‐specific mortality in patients with epilepsy. Methods Patients with epilepsy and a random 10:1 sample without epilepsy were extracted from The ClinicAl research using LInked Bespoke studies and Electronic health Records (CALIBER) resource. The hazard ratio (HR) of all‐cause and possible seizure‐specific mortality, treating SRI use as a time‐varying covariate, was determined using the date of a second SRI prescription as exposure and in discrete 6‐month periods over the entire duration of follow‐up. We used Cox regression and competing risk models with Firth correction to calculate the HR. We controlled for age, sex, depression, comorbidity, (Charlson comorbidity index) and socioeconomic status (Index of Multiple Deprivation). Results We identified 2,718,952 eligible patients in CALIBER, of whom 16,379 (0.60%) had epilepsy. Median age and follow‐up were 44 (interquartile range [IQR] 29–61]) and 6.4 years (IQR 2.4–10.4 years), respectively, and 53% were female. A total of 2,178 patients (13%) had at least two SRI prescriptions. Hazard of all‐cause mortality was significantly elevated following a second prescription for an SRI (HR 1.64 95% confidence interval [95% CI] 1.44–1.86; p