title: Efficacy and safety of doxepin 3 and 6 mg in a 35-day sleep laboratory trial in adults with chronic primary insomnia.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of doxepin (DXP) 3 mg and 6 mg in adults diagnosed with primary insomnia.
  
  
  METHODS
  The study was a randomized, double-blind, parallel-group, placebo-controlled trial. Patients meeting DSM-IV-TR criteria for primary insomnia were randomized to 35 days of nightly treatment with DXP 3 mg (n=75), DXP 6 mg (n=73), or placebo (PBO; n=73), followed by 2 nights of single-blind PBO to evaluate discontinuation (DC) effects. Efficacy was assessed using polysomnography (PSG) and patient reports. Efficacy data were examined for Night (N) 1, N15, and N29. Safety assessments were conducted throughout the study.
  
  
  RESULTS
  Compared with PBO, DXP 3 and 6 mg significantly improved wake time after sleep onset (WASO) on N1 (3 mg and 6 mg; P<0.0001), N15 (3 mg P=0.0025; 6 mg P=0.0009), and N29 (3 mg P=0.0248; 6 mg P=0.0009), latency to persistent sleep (LPS) on N1 (3 mg P=0.0047; 6 mg P=0.0007), and total sleep time (TST) on N1 (3 mg and 6 mg P<0.0001), N15 (6 mg P=0.0035), and N29 (3 mg P=0.0261; 6 mg P<0.0001). In terms of early morning awakenings, DXP 3 and 6 mg demonstrated significant improvements in SE in the final quarter of the night on N1, N15, and N29, with the exception of 3 mg on N29 (P=0.0691). Rates of discontinuation were low, and the safety profiles were comparable across the 3 treatment groups. There were no significant next-day residual effects, and there were no spontaneous reports of memory impairment, complex sleep behaviors, anticholinergic effects, weight gain, or increased appetite. Additionally, there was no evidence of rebound insomnia after DXP discontinuation.
  
  
  CONCLUSIONS
  Five weeks of nightly administration of DXP 3 mg and 6 mg to adults with chronic primary insomnia resulted in significant and sustained improvements in sleep maintenance and early morning awakenings (with the exception of SE in the final quarter of the night on N29 for 3 mg [P=0.0691]). These sleep improvements were not accompanied by next-day residual effects or followed by rebound insomnia or withdrawal effects upon discontinuation. These findings confirm the unique profile of sleep maintenance efficacy and safety of DXP observed in prior studies.
authors.affiliation: Duke University School of Medicine, Durham, NC 27710, USA. kryst001@mc.duke.edu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Krystal
authors.forename: Alan
authors.initials: A
authors.lastname: Lankford
authors.forename: H Heith
authors.initials: HH
authors.lastname: Durrence
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ludington
authors.forename: Philip
authors.initials: P
authors.lastname: Jochelson
authors.forename: Roberta
authors.initials: R
authors.lastname: Rogowski
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D004311:Double-Blind Method; D004316:Doxepin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017286:Polysomnography / Q000187:drug effects; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D004316:Doxepin