Possibility that certain hypnotics might cause cancer in skin.
Fifteen epidemiologic studies have associated hypnotic drugs with excess mortality, especially excess cancer deaths. Until recently, insufficient controlled trials were available to demonstrate whether hypnotics actually cause any cancers. The US Food and Drug Administration (FDA) Approval History and Documents were accessed for zaleplon, eszopiclone and ramelteon. Since zolpidem was used as a comparison drug in zaleplon trials, some zolpidem data were also available. Incident cancers occurring during randomized hypnotics administration or placebo administration were tabulated. Combining controlled trials for the four drugs, there were 6190 participants given hypnotics and 2535 given placebo in parallel. There were eight mentions of incident non-melanoma skin cancers among participants receiving hypnotics but no comparable mentions of cancers among those receiving placebo (P = 0.064, one-tailed). There were also four mentions of incident tumors of uncertain malignancy among those receiving hypnotics but none among those receiving placebo, so combining uncertain and definite malignancies yielded a more significant contrast (P = 0.016). FDA files revealed that all four of the new hypnotics were associated with cancers in rodents. Three had been shown to be clastogenic. Together with the epidemiologic data and laboratory studies, the available evidence signals that new hypnotics may increase cancer risk. Due to limitations in available data, confirmatory research is needed.
Department of Psychiatry, University of California, San Diego and The Scripps Clinic Sleep Center, La Jolla, California 92093-0667, USA. dkripke@ucsd.edu
Daniel F
DF
Kripke
D000081:Acetamides / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D053961:Azabicyclo Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D002280:Basal Cell Carcinoma / Q000139:chemically induced* / Q000453:epidemiology; D015984:Causality; D003430:Cross-Sectional Studies; D000069582:Eszopiclone; D005500:Follow-Up Studies; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D015994:Incidence; D007192:Indenes / Q000009:adverse effects* / Q000627:therapeutic use; D008545:Melanoma / Q000139:chemically induced* / Q000453:epidemiology; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000453:epidemiology; D014481:United States; D014486:United States Food and Drug Administration; D000077334:Zolpidem
D000081:Acetamides; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D007192:Indenes; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D000077334:Zolpidem; C495910:ramelteon; C085665:zaleplon; D000069582:Eszopiclone