RESUMO
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. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Clinical research site. PATIENTS: Fifteen patients with moderate-to-severe chronic low back pain requiring long-term opioid analgesia. INTERVENTIONS: 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. OUTCOME MEASURES: 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.