To the Editor: We appreciate the clinical insights of Dr. Modesto-Lowe regarding the potential dangers of divided methadone dosing. As noted in the editorial, split dosing should not be taken lightly. Patients should be carefully assessed prior to initiating divided dosing. Evidence of withdrawal, including craving, should initially be treated with an increase in daily dosing. If further methadone increases produce clinically unacceptable side effects (i.e., sedation or impairment in performance that prevents safe driving or working) and a working rapport has been established between the patient and physician, then divided dosing should be considered. Patients should first be assessed for rapid methadone metabolism as a result of enzymatic variants, concomitant medications, and/or pregnancy. Prior to implementation, patients should be informed that split dosing will be maintained only if urine drug toxicology screens are negative and withdrawal symptoms abate, the latter offering presumptive evidence that the divided dose is being consumed and is therapeutically appropriate. Questionnaires such as the Opiate Dosage Adequacy Scale can be useful (1).
Nevertheless, some concerns may be overstated. The excellent review article (2) Dr. Modesto-Lowe references noted that the recent increase in police methadone seizures in the United States has been for tablets dispensed for pain management, not the liquid used for methadone maintenance treatment. Further, the Center for Substance Abuse Treatment (3) documents the following:
The greatest incremental growth in methadone distribution in recent years is associated with use of the drug as an analgesic and its distribution through pharmacies. In fact, the distribution of solid methadone formulations (tablets and diskettes), primarily through pharmacies, has surpassed distribution of the liquid formulations that are the mainstay of dispensing in OTPs [opioid treatment programs]. From 1998 through 2002, the volume of methadone distributed through pharmacies increased five-fold, whereas the volume distributed through OTPs increased only 1.5-fold. In 2002 alone, pharmacies accounted for 88 percent of all purchases of methadone tablets (DEA, 2003)….Examination of the data available to the National Assessment participants indicates that OTPs and the 2001 regulatory changes did not have a significant effect on rates of methadone-associated mortality….In the cases in which the sources of methadone associated with deaths could be traced, OTPs did not appear to be involved (1).
The increase in methadone prescription practices appears to be a combination of increasing recognition of the importance of adequate pain relief coupled with concerns over the use of Oxycontin, resulting in a switch to methadone.
Dr. Modesto-Lowe’s concern that the judicious and occasional use of divided methadone dosing may lead to methadone-maintained craving-free individuals “nodding off, robbing banks, and using cocaine and benzodiazepines” evokes memories of “reefer madness” and has little support from empirical evidence. Patients who are sedated should not be provided divided dosing, appropriately medicated patients on opioid agonist therapy experience a dramatic decrease in crime, and most studies indicate a decrease, not an increase, in nonopioid drug use among methadone-maintained individuals.
1.González-Saiz F, Rojas OL, Gómez RB, Acedos IB, Martínez JG, Collantes MAG, Fernández AL, Group SMLS: Evidence of reliability and validity of the Opiate Dosage Adequacy Scale (ODAS) in a sample of methadone maintenance patients. Heroin Addict Relat Clin Probl 2008; 10:25–38
2.Corkery JM, Schifano F, Ghodse AH, Oyefeso A: The effects of methadone and its role in fatalities. Hum Psychopharmacol 2004; 19:565–576
3.Center for Substance Abuse Treatment (ed): Methadone-Associated Mortality: Report of a National Assessment, May 8–9, 2003. SAMHSA Publication No. 04–3904. Rockville, Md, SAMHSA, 2003 (http://www:methadone:net/Documents/Methadone_Associated_Mortality.htm)
Dr. Adinoff’s disclosures accompany the original editorial. Dr. Schuster has served as a consultant to AstraZeneca, Merck, Orexo, Ortho-McNeil, Shire, and Takeda; and he has a contract for postmarketing surveillance studies with Reckitt Benckiser for Suboxone, Subutex, and Buprinex.
This letter (doi: 10.1176/appi.ajp.2008.08040586r) was accepted for publication in June 2008.
Reprints are not available; however, Letters to the Editor can be downloaded at http://ajp.psychiatryonline.org.