"Methadone and Benzodiazepines May Increase Severity of Snoring: Presented at AAPM"
By Crystal Phend
SAN DIEGO, CA -- February 27, 2006 -- Chronic pain patients who are on opioid therapy appear to have a dramatically higher rate of sleep apnea than the general population, and methadone and benzodiazepines appear to increase its severity, researchers reported here February 23[rd at the 22nd Annual Meeting of the American Academy of Pain Medicine (AAPM).
"It looks like the medications could be a major factor," said lead author Lynn R. Webster, MD, medical director of Lifetree Clinical Research in Salt Lake City, Utah.
Opioid drugs were found to be associated with sleep-disordered breathing in recent studies, so Dr. Webster and colleagues examined the relationship in patients on chronic opioid therapy.
The researchers retrospectively examined medical charts of 152 consecutive chronic pain patients receiving moderate to high doses of opioid medications. No prospective data were available on whether patients had sleep-disordered breathing before beginning opioid therapy or before the study began.
All patients received a polysomnogram with sensors to detect rib and abdominal effort while breathing and the rate of air flow through the nostrils. Apnea-hypopnea index and central apnea index were evaluated according to American Academy of Sleep Medicine criteria and were adjusted for age, gender, and body mass index.
Nearly all patients took long-acting opioids (96%) while 33% were on long-acting opioids and methadone. A little more than a third of patients took benzodiazepines (36%) and anticonvulsants (34%). Twenty-eight percent took muscle relaxants; 16% took stimulants.
Overall, 75% of patients had abnormal apnea-hypopnea index scores: 43% had obstructive sleep apnea, 24% had central sleep apnea, and 8% had both obstructive sleep apnea and central sleep apnea.
Comparatively, only 17% to 24% of the general population has some form of sleep-disordered breathing, Dr. Webster said.
As expected, body mass index was correlated with apnea-hypopnea, but muscle relaxants and methadone were also significant factors (P = .034 and P = .037, respectively). Only methadone and benzodiazepines were significantly associated with central sleep apnea in a multivariate analysis (P = .004 and P = .042, respectively).
Dr. Webster said the data suggests a dose response between methadone and the severity of sleep apnea as well as an additive effect from benzodiazepines. However, the real reason for the association is unknown. "I'm convinced there's a problem," he said. "I don't know what the problem is."
Methadone may affect mu opioid receptor mechanisms involved in respiratory depression, he said, or the reason could simply be that chronic pain patients are somehow more likely to have sleep-disordered breathing problems.
Whatever the cause, the data suggest that physicians should be alert to sleep apnea in their chronic pain patients.
"I think doctors … ought to be more liberal with ordering sleep studies," Dr. Webster said, since these breathing problems may contribute to unintended deaths.
He cautioned against withdrawing opioid medications based on the preliminary study. The researchers plan to conduct a similar prospective study with sleep tests performed before initiation of opioid therapy.
[Presentation title: Sleep Apnea Associated with Methadone and Benzodiazepine Therapy. Poster 165]
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