title: Comparative effects of morning vs. evening dosing of extended-release hydromorphone on sleep physiology in patients with low back pain: a pilot study.
abstract: OBJECTIVE
  To investigate effects of extended-release (ER) hydromorphone dosing time (morning, QAM; evening, QPM) on sleep physiology in patients with chronic low back pain.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, crossover trial.
  
  
  METHODS
  Clinical research site.
  
  
  METHODS
  Fifteen patients with moderate-to-severe chronic low back pain requiring long-term opioid analgesia.
  
  
  METHODS
  Following an open-label immediate-release (IR) hydromorphone titration phase, patients received once-daily ER hydromorphone QAM or QPM for at least 14 days and then crossed over to the alternate regimen. Overnight polysomnographic sleep studies were performed at baseline, following IR hydromorphone titration, and following each ER hydromorphone dosing period.
  
  
  METHODS
  The primary outcome measure was prevalence of nocturnal apnea-hypopnea index (AHI). Other evaluations included central apnea index and obstructive apnea index; Short-Form McGill Pain Questionnaire; a modified Medical Outcomes Study sleep scale, patient responses in a daily diary, and adverse event safety profiles.
  
  
  RESULTS
  Mean AHI scores were lower following QAM rather than QPM dosing, but not significantly (12.9 vs. 17.1, P > 0.05). Secondarily, QAM dosing resulted in numerically fewer apnea episodes and improvements in pulse oximetry measures; however, these differences were not significant (P > 0.05). Sleep quality/quantity and pain measures were improved with opioid therapy overall, particularly QPM dosing, without significantly compromising safety.
  
  
  CONCLUSIONS
  ER hydromorphone QAM dosing may be preferred if sleep-disordered breathing associated with ongoing opioid therapy is of concern; however, QPM dosing may be advantageous in terms of pain relief and quality/quantity of sleep. Further research is recommended to provide more definitive clinical guidance.
authors.affiliation: PRA Healthsciences, Salt Lake City, Utah, USA.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Webster
authors.forename: Michael D
authors.initials: MD
authors.lastname: Smith
authors.forename: Sam
authors.initials: S
authors.lastname: Mackin
authors.forename: Matthew
authors.initials: M
authors.lastname: Iverson
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage* / Q000009:adverse effects; D017116:Low Back Pain / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017286:Polysomnography / Q000379:methods; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004091:Hydromorphone
keywords: Apnea-Hypopnea Index; Central Sleep Apnea; Hydromorphone; Noncancer Pain; Obstructive Sleep Apnea; Opioids; Polysomnography