Dr. Amanda A. Beck and her colleagues were puzzled by some of their patients at the University of New Mexico's Sleep Disorders Center in Albuquerque. The patients took methadone, but they did not have histories of drug abuse. They were middle-class baby boomers under treatment for chronic pain, and their nighttime breathing problems were severe.
They needed a variable positive airway pressure device, the VPAP Adapt, recently approved for the treatment of central sleep apnea, mixed sleep apnea, and periodic breathing. "We are getting this very complicated sleep-disordered breathing, which used not to be in our lexicon," Dr. Beck, director of adult services, said at a university-sponsored psychiatric symposium, where she described her center's experience as a red flag for methadone prescribers.
Concern about accidental deaths from methadone use is long-standing. Reports linking methadone to sleep-disordered breathing are a recent and, as yet, poorly understood phenomenon. Dr. Beck said her group and other sleep centers are documenting cases of sleep-disordered breathing in methadone patients, now estimated at one per week in her clinic.
The Food and Drug Administration has responded to concern over methadone related deaths and complications with an advisory. (See related story, p. 2.)
Several studies of the complication have been published, but most accounts are anecdotal. Some reports focus on patients on methadone maintenance, while others address the growing number of people taking opioids for chronic pain. (See box.)
In 2003, physicians at the Intermountain Sleep Disorders Center in Salt Lake City described ataxic breathing, central apnea, sustained hypoxemia, and other abnormalities in three patients on long-term opioid therapy for pain (Chest 2003;123:632-9).
That article spurred Dr. Lynn R. Webster to order sleep studies on patients prescribed opioid therapies at the Lifetree Pain Clinic in Salt Lake City. Dr. Webster, medical director of the clinic and its affiliated research center, presented polysomnography data on 152 patients at the American Academy of Pain meeting in February 2006.
Three-fourths of the patients had an abnormal apnea-hypopnea index, including 42% with obstructive sleep apnea, 12% with central sleep apnea, and 21% with mixed obstructive and central sleep apnea. One-third of the patients had been prescribed methadone and long-acting opioids; 4% took only methadone, according to the abstract.
In another study that Dr. Webster presented at the same meeting, he compared polysomnography data on 73 opioid-naive primary care patients who had been referred for sleep studies with data on 139 asymptomatic chronic pain patients taking opioids. In both groups, 36% of the patients had severe sleep apnea.
Obstructive sleep apnea was more common in the primary care patients at 89%, vs. 77% of cases in the pain group. Central sleep apnea, a more severe condition, occurred more in the pain patients: 32%, vs. 6% of the primary care cases.
As a result of his ongoing research, Dr. Webster has become a campaigner for more conservative use of methadone. "No one was aware this was a problem. Most pain practices would not ordinarily order sleep studies," he said in an interview with this newspaper.
Dr. Webster emphasized that he is not opposed to methadone use for pain management. "But patients and physicians need to understand it is not like other opioids."
Recent reports have also associated methadone with poor sleep quality in addiction patients at maintenance programs.
A U.S. study reported that 84% of 225 patients were "poor" sleepers with Pittsburgh Sleep Quality Index scores of 6 or higher (J. Subst. Abuse Treat. 2004;26:175-80).
Israeli researchers found that 75% of 102 patients were poor sleepers (Drug Alcohol Depend. 2006;82:103-10).
Searching for Mechanisms
Looking for sleep-disordered breathing (SDB), an Australian group reported that 30% of 50 stable methadone maintenance patients had central sleep apnea. …