Increased mortality in narcolepsy.

OBJECTIVE: To evaluate the mortality rate in patients with narcolepsy. DESIGN: Data were derived from a large database representative of the US population, which contains anonymized patient-linked longitudinal claims for 173 million individuals. SETTING: Symphony Health Solutions (SHS) Source Lx, an anonymized longitudinal patient dataset. PATIENTS/PARTICIPANTS: All records of patients registered in the SHS database between 2008 and 2010. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Identification of patients with narcolepsy was based on ≥ 1 medical claim with the diagnosis of narcolepsy (ICD-9 347.xx) from 2002 to 2012. Dates of death were acquired from the Social Security Administration via a third party; the third party information was encrypted in the same manner as the claims data such that anonymity is ensured prior to receipt by SHS. Annual all-cause mortality rates for 2008, 2009, and 2010 were calculated retrospectively for patients with narcolepsy and patients without narcolepsy in the database, and standardized mortality ratios (SMR) were calculated. Mortality rates were also compared with the general US population (Centers for Disease Control data). SMRs of the narcolepsy population were consistent over the 3-year period and showed an approximate 1.5-fold excess mortality relative to those without narcolepsy. The narcolepsy population had consistently higher mortality rates relative to those without narcolepsy across all age groups, stratified by age decile, from 25-34 years to 75+ years of age. The SMR for females with narcolepsy was lower than for males with narcolepsy. CONCLUSIONS: Narcolepsy was associated with approximately 1.5-fold excess mortality relative to those without narcolepsy. While the cause of this increased mortality is unknown, these findings warrant further investigation.

Utilization of topiramate during pregnancy and risk of birth defects.

OBJECTIVE: To evaluate the risk of oral cleft and major congenital malformation occurrence in infants born to women exposed to topiramate in their first trimester of pregnancy compared with women who used other anti-epileptic drugs or those with disease states in which topiramate may have been used. METHODS: Sourced from patients' pharmacy and medical claims from 2002 through 2010, this study identified infants born from mothers exposed to topiramate (n = 870) and other anti-epileptic drugs (n = 3615) in the first trimester of pregnancy. First trimester exposure was based on prescription dispensing dates and days supplied relative to infant birth date, accounting for premature delivery. Infants born to women with migraine without epilepsy (n = 26,865), women with epilepsy (n = 2607), and women with diabetes mellitus (n = 13,062), as well as randomly sampled women (n = 99,761), were used for comparison. Topiramate use was excluded from all groups with the exception of the topiramate and random sample cohorts. Non-anti-epileptic drug teratogens were excluded from each cohort (except random sample). Unadjusted relative risks and 95% confidence intervals for topiramate vs each comparator were calculated. Risks >1 indicate a higher risk with topiramate vs comparator, whereas risks <1 indicate a lower risk with topiramate vs comparator. RESULTS: The frequency of oral clefts was 0.23% for topiramate use, 0.17% for other anti-epileptic drug use (topiramate vs comparator relative risk = 1.39 [95% confidence interval: 0.28-6.85]), 0.16% for migraineurs (1.47 [0.36-6.06]), 0.31% for epileptics (0.75 [0.16-3.52]), 0.26% for diabetics (0.88 [0.21-3.67]), and 0.16% for the random sample (1.44 [0.36-5.81]). The frequency of major congenital malformations was 4.33% for topiramate use, 3.21% for other anti-epileptic drugs (1.33 [0.92-1.90]), 3.79% for migraineurs (1.12 [0.81-1.55]), 4.33% for epileptics (0.98 [0.68-1.41]), 6.58% for diabetics (0.65 [0.47-0.89]), and 3.77% for the random sample (1.13 [0.82-1.55]). CONCLUSIONS: This retrospective study quantified the association between topiramate exposure during pregnancy and the risk of oral cleft or major congenital malformations, and suggested little or no increase in risk in comparison with exposure to other anti-epileptic drugs or to disease states, such as migraine, epilepsy, or diabetes. However, small numbers of events limit the strength of inferences.