INTRODUCTION: The use of opioids in the United States has had an exponential growth over that past decade. In 2001, Teichtahl described a high prevalence of sleep-disordered breathing, predominately central apneas, among patients in a methadone maintenance program.1 However, to date, there is little information on the mechanisms responsible for central sleep apnea in patients receiving chronic opiates. In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone sublingual tablets as a treatment option in opioid dependence. Because of its low risk of respiratory depression and abuse, buprenorphine-naloxone is available as a Schedule III controlled medication.2 We describe a patient taking buprenorphine-naloxone found to have a significant amount of central sleep apnea episodes.
CASE PRESENTATION: We report a case of a 30 year-old man who was referred to our sleep center for evaluation of symptoms of excessive daytime sleepiness and non-restorative sleep for seven years. He noticed that in the past two years, his symptoms had become progressively worse and that he had developed snoring and respiratory pauses during sleep. His Epworth Sleepiness Scale was 16 out of 24. His past medical history includes hypertension, gastroesophageal reflux disease, depression and history of narcotic abuse. His daily medications include buprenorphine-naloxone 2 mg, citalopram, pantoprazol, metoprolol, and lamotrigine. On physical examination, he had a BMI of 28.6 kg/m2. The physical exam was normal. Initial overnight polysomnography was performed using standards of the American Academy of Sleep Medicine. Sleep architecture revealed a total sleep time of 7.8 hours. The quantity and percentage of NREM sleep and REM sleep were all within normal for his age. A total of 273 central apneas, 28 hypopneas, and 270 obstructive apneas were noted, for an overall apnea/hypopnea index (AHI) of 38.7 events per hour.
DISCUSSIONS: Buprenorphine-naloxone comprises the partial mu-opioid receptor agonist buprenorphine in combination with the opioid antagonist naloxone in a 4:1 ratio, which has been found to be effective in the treatment of opioid dependence. In our patient, we believe that the distinctive breathing pattern of central apnea observed is due to his chronic use of buprenorphine-naloxone. Unlike other causes of central sleep apnea (CSA), our patient was young and did not present with symptoms suggestive of congestive heart failure nor any type of neurological disease. While the treatment of obstructive sleep apnea syndrome is straightforward and usually successful with continuous positive airway pressure or bilevel positive airway pressure therapy, treatment of sleep apnea with CSA is not universally agreed upon. In our patient, whose baseline polysomnography noted an equivalent amount of both central and obstructive sleep apnea, Adaptive Servo-Ventilation was effective in eliminating both the central apneic respiratory events as well as the obstructive respiratory events.
CONCLUSION: With the prevalence of opioid addiction on the rise and the development of effective treatments for opioid addiction, such as buprenorphine-naloxone, we suggest that long term use may have a significant impact on sleep-disordered breathing, as demonstrated by our case report. As support for office-based treatment with buprenorphine-naloxone is growing and being more readily available, it may be prudent to monitor patients who receive this therapy for the development of sleep-disordered breathing.
DISCLOSURE: Larry Ladi, No Financial Disclosure Information; No Product/Research Disclosure Information