title: Rebound insomnia and elimination half-life: assessment of individual subject response.
abstract: Following abrupt withdrawal of five benzodiazepine hypnotics, the presence of rebound insomnia on individual subject nights was evaluated in comparison to a placebo group. During the first three nights of withdrawal, the frequency of occurrence of rebound insomnia for drugs with relatively rapid rates of elimination (triazolam, midazolam, and lormetazepam) was significantly higher than that for the placebo control group. In contrast, the frequency of withdrawal sleep difficulty for two slowly eliminated hypnotics (flurazepam and quazepam) was similar to that of the placebo control group during each of five successive three-night segments of a 15-night withdrawal period. These findings, based on individual subject-night data, confirm and extend previous reports using group mean values that demonstrate a frequent, immediate, and intense degree of rebound insomnia following abrupt withdrawal of relatively rapidly eliminated hypnotic drugs and an infrequent, delayed, and milder degree of sleep difficulty following withdrawal of slowly eliminated drugs.
authors.forename: E O
authors.initials: EO
authors.lastname: Bixler
authors.forename: J D
authors.initials: JD
authors.lastname: Kales
authors.forename: A
authors.initials: A
authors.lastname: Kales
authors.forename: J A
authors.initials: JA
authors.lastname: Jacoby
authors.forename: C R
authors.initials: CR
authors.lastname: Soldatos
mesh_terms: D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000378:metabolism; D001569:Benzodiazepines / Q000009:adverse effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005479:Flurazepam / Q000009:adverse effects / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008140:Lorazepam / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism; D008874:Midazolam; D008875:Middle Aged; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013997:Time Factors; D014229:Triazolam / Q000009:adverse effects / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D014229:Triazolam; C023842:lormetazepam; D005479:Flurazepam; C025130:quazepam; D008140:Lorazepam; D008874:Midazolam