Divided Doses for Methadone Maintenance

To the Editor: In his editorial, published in the March 2008 issue of the Journal , Bryon Adinoff, M.D. (1) suggests that among addiction specialists, there is worldwide consensus regarding the beneficial effects of methadone maintenance on improving the morbidity and mortality of opioid-dependent populations. Methadone maintenance decreases rates of HIV, hepatitis C, and heroin overdoses. However, a significant number of opioid-dependent individuals do not respond to methadone. In the United States, efforts to improve the clinical usefulness of opioid agonist maintenance resulted in the Food and Drug Administration’s approval of buprenorphine for use in primary care settings. Moreover, Dr. Adinoff’s editorial discussed the potential merits of divided daily doses for methadone maintenance. However, there are possible limitations to this approach as well as related public health implications.

From a public health perspective, the most compelling obstacle in employing this strategy relates to an increase in methadone deaths in various regions within the United States (2) . The role of methadone diversion in these fatalities is suggested by an expanding methadone black market, fostering its use among opioid-naive populations (2) . Unfortunately, existing systems designed to curtail diversion remain in need of urgent improvement. Meanwhile, dividing daily methadone doses in already understaffed methadone clinics could lead to a relaxation of methadone take-home policies. Can we afford to pay the price of worsening diversion in the midst of an epidemic of prescription opioid abuse? Until the magnitude of the diversion problem improves, methadone clinics are unlikely to embrace the splitting of doses, regardless of its clinical utility.

Another aspect of the editorial that has been overlooked is the premise that craving is an essential precursor to drug use. In Dr. Adinoff’s words, even the most sophisticated neuroimaging study will have limited clinical value, and only patient endorsement of craving can help dosing strategies. Despite this premise, it is important to acknowledge that the definition, measurements, and clinical value of craving have been the subject of much controversy (3) . Nevertheless, craving remains widely employed to estimate dosing requirements in methadone clinics. From a clinical perspective, self-reports of craving appear to be most useful, combined with objective measures of functioning. If methadone-maintained, craving-free individuals are nodding off, robbing banks, and using cocaine and benzodiazepines, then the protective value of methadone as well as its credibility among the public declines, irrespective of research findings.