title: Efficacy and safety of as-needed, post bedtime dosing with indiplon in insomnia patients with chronic difficulty maintaining sleep.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of immediate release indiplon capsules in patients with chronic insomnia using an "as-needed" dosing strategy in response to difficulty falling back to sleep following a middle of the night, nocturnal awakening.
  
  
  METHODS
  Adult outpatients (N=264; 71% female; age, 46 years) who met DSM-IV criteria for primary insomnia, with average total sleep time (TST) < 6.5 hours and >8 nights in the past month with nocturnal awakenings, were randomized to 4 weeks of double-blind treatment with 10 mg or 20 mg indiplon capsules, or placebo. The primary endpoint was latency to sleep onset post-dosing after a middle of the night awakening (LSOpd). Secondary endpoints included patients' subjective assessment of total sleep time (sTSTpd). Next day residual effects were evaluated by a 100 mm Visual Analog Scale (VAS) rating of sleepiness.
  
  
  RESULTS
  Both doses of indiplon significantly reduced LSOpd at all time-points. Compared to placebo (45.2 min), the 4-week least squares (LS) mean LSOpd was 36.5 min in the indiplon 10 mg group (P = 0.0023) and 34.4 min in the indiplon 20mg group (P < 0.0001). The 4-week LS mean sTSTpd was higher in the indiplon 10 mg group (253 min) and 20mg group (278 min) compared to placebo (229 min; P < 0.01 for both comparisons). There was no increase observed in VAS ratings of next-day sleepiness for either dose of indiplon when compared to placebo. Indiplon was well-tolerated at both doses.
  
  
  CONCLUSIONS
  Patients with chronic insomnia with nocturnal awakenings achieved significant and sustained improvement in sleep parameters while utilizing an as-needed post bedtime dosing strategy with indiplon capsules. Indiplon was well-tolerated, with no self-rated, next-day residual effects.
authors.affiliation: Sleep Disorders and Research Center, Department of Psychiatry and Behavioral Neurosciences Henry Ford Hospital, 2799 West Grand Blvd, CEP-3, Detroit, MI 48202, USA. troth1@hfhs.org
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.forename: Gary K
authors.initials: GK
authors.lastname: Zammit
authors.forename: Martin B
authors.initials: MB
authors.lastname: Scharf
authors.forename: Robert
authors.initials: R
authors.lastname: Farber
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D017060:Patient Satisfaction; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects
chemical_list: D006993:Hypnotics and Sedatives; D013876:Thiophenes; D001569:Benzodiazepines; C469870:indiplon