{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:56:30Z","timestamp":1791251790403,"version":"4.1.0"},"reference-count":41,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2012,1,20]]},"published-print":{"date-parts":[[2012]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>An estimated 6%\u201310% of US adults took a hypnotic drug for poor sleep in 2010. This study extends previous reports associating hypnotics with excess mortality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>A large integrated health system in the USA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Longitudinal electronic medical records were extracted for a one-to-two matched cohort survival analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Subjects<\/jats:title>\n                  <jats:p>Subjects (mean age 54\u2008years) were 10\u2008529 patients who received hypnotic prescriptions and 23\u2008676 matched controls with no hypnotic prescriptions, followed for an average of 2.5\u2008years between January 2002 and January 2007.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main outcome measures<\/jats:title>\n                  <jats:p>Data were adjusted for age, gender, smoking, body mass index, ethnicity, marital status, alcohol use and prior cancer. Hazard ratios (HRs) for death were computed from Cox proportional hazards models controlled for risk factors and using up to 116 strata, which exactly matched cases and controls by 12 classes of comorbidity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>As predicted, patients prescribed any hypnotic had substantially elevated hazards of dying compared to those prescribed no hypnotics. For groups prescribed 0.4\u201318, 18\u2013132 and &gt;132 doses\/year, HRs (95% CIs) were 3.60 (2.92 to 4.44), 4.43 (3.67 to 5.36) and 5.32 (4.50 to 6.30), respectively, demonstrating a dose\u2013response association. HRs were elevated in separate analyses for several common hypnotics, including zolpidem, temazepam, eszopiclone, zaleplon, other benzodiazepines, barbiturates and sedative antihistamines. Hypnotic use in the upper third was associated with a significant elevation of incident cancer; HR=1.35 (95% CI 1.18 to 1.55). Results were robust within groups suffering each comorbidity, indicating that the death and cancer hazards associated with hypnotic drugs were not attributable to pre-existing disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Receiving hypnotic prescriptions was associated with greater than threefold increased hazards of death even when prescribed &lt;18 pills\/year. This association held in separate analyses for several commonly used hypnotics and for newer shorter-acting drugs. Control of selective prescription of hypnotics for patients in poor health did not explain the observed excess mortality.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2012-000850","type":"journal-article","created":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T00:55:37Z","timestamp":1330390537000},"page":"e000850","source":"Crossref","is-referenced-by-count":343,"title":["Hypnotics' association with mortality or cancer: a matched cohort study"],"prefix":"10.1136","volume":"2","author":[{"given":"Daniel F","family":"Kripke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D","family":"Langer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence E","family":"Kline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2012,2,27]]},"reference":[{"key":"2025101813062136000_2.1.e000850.1","unstructured":"International Narcotics Control Board. 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