Correspondence

Office-Based Treatment of Opioid-Dependent Patients

N Engl J Med 2003; 348:81-82January 2, 2003

Article

To the Editor:

Fiellin and O'Connor (Sept. 12 issue)1 note that 40 percent of British prescriptions for methadone are written by general practitioners (family doctors). They fail to mention the dangers of this practice.

The number of methadone-associated deaths in England and Wales rose from 371 in 1993 to 675 in 1997, when it was the most common cause of death associated with drug misuse.2 Nonfatal overdosing is common: in the past 21 months, there have been 51 cases of methadone overdose treated in our hospital alone, and several have required intensive care. The first two weeks of treatment are particularly dangerous3 because methadone has a long half-life and therefore a cumulative effect, its therapeutic range is narrow, and it is difficult to predict the correct starting dose for a patient. More lives may have been lost through the prescription of methadone than have been saved.3

When the administration of prescribed methadone is not supervised, considerable quantities are diverted by sale or gift to abusers for whom it is not prescribed. This practice accounts for a high proportion of methadone-associated deaths in England4 and Australia.3 Moreover, some children died when parents left their methadone within reach.5

Robin Esmond Ferner, M.D., F.R.C.P.
Anthony M. Daniels, M.B., M.R.C.Psych.
City Hospital, Birmingham B18 7QH, United Kingdom

5 References

1. 1

   Fiellin DA, O'Connor PG. Office-based treatment of opioid-dependent patients. N Engl J Med 2002;347:817-823
   Full Text | Web of Science | Medline

2. 2

   Methadone. In: Reducing drug related deaths: a report by the Advisory Council on the Misuse of Drugs. London: Stationery Office, 2000:61-8.
   

3. 3

   Caplehorn JR, Drummer OH. Mortality associated with New South Wales methadone programs in 1994: lives lost and saved. Med J Aust 1999;170:104-109
   Web of Science | Medline

4. 4

   Cairns A, Roberts ISD, Benbow EW. Characteristics of fatal methadone overdose in Manchester, 1985-94. BMJ 1996;313:264-265
   CrossRef | Web of Science | Medline

5. 5

   Binchy JM, Molyneux EM, Manning J. Accidental ingestion of methadone by children in Merseyside. BMJ 1994;308:1335-1336
   CrossRef | Web of Science | Medline

Author/Editor Response

Ferner and Daniels describe the adverse consequences that can occur with methadone diversion. We share their concern and in our article indicate that the development of systems to minimize diversion is a challenge to the implementation of office-based treatment of opioid dependence. We describe a model of office-based methadone treatment for stabilized patients for whom dose induction and responsibility with unsupervised administration are established.

Despite concerns about diversion, there is compelling evidence that the benefits of expanding access to maintenance treatment with opioid agonists exceed the risks. The efficacy of opioid-agonist treatment in decreasing illicit use of opiates, promoting treatment retention, and decreasing the infectious complications of injection-drug use has been demonstrated during the past 30 years.1 Recently, the provision of maintenance treatment was correlated with a 75 percent decrease in the number of fatal heroin overdoses in France, from 564 in 1994 to 143 in 1998.2 The rates of death from heroin overdose are higher among untreated opioid-dependent persons than among persons who are treated.3,4 A meta-analysis revealed a relative risk of death of 0.25 (95 percent confidence interval, 0.19 to 0.33) among patients receiving methadone maintenance therapy.3

On October 8, 2002, the Food and Drug Administration approved the sublingual buprenorphine–naloxone combination for the treatment of opioid dependence, providing an alternative to methadone for unsupervised administration and office-based practice.5 Because buprenorphine is a partial mu agonist, its safety profile is more favorable than that of methadone. Inappropriate injection of naloxone precipitates opioid withdrawal, thus decreasing the likelihood of diversion of buprenorphine–naloxone. Office-based treatment of opioid dependence offers the promise of treatment for patients who are currently untreated for this medical condition with its attendant morbidity and mortality.

David A. Fiellin, M.D.
Patrick G. O'Connor, M.D., M.P.H.
Yale University School of Medicine, New Haven, CT 06520-8025
david.fiellin@yale.edu

5 References

1. 1

   O'Connor PG, Fiellin DA. Pharmacologic treatment of heroin-dependent patients. Ann Intern Med 2000;133:40-54
   Web of Science | Medline

2. 2

   Lepere B, Gourarier L, Sanchez M, et al. Diminution du nombre de surdoses mortelles à l'héroïne, en France, depuis 1994: à propos du rôle des traitements de substitution. Ann Med Intern 2001;152:Suppl 3:IS5-IS12
   Medline

3. 3

   Caplehorn JR, Dalton MS, Haldar F, Petrenas AM, Nisbet JG. Methadone maintenance and addicts' risk of fatal heroin overdose. Subst Use Misuse 1996;31:177-196
   CrossRef | Web of Science | Medline

4. 4

   Zanis DA, Woody GE. One-year mortality rates following methadone treatment discharge. Drug Alcohol Depend 1998;52:257-260
   CrossRef | Web of Science | Medline

5. 5

   Fiellin DA, Pantalon MV, Pakes JP, O'Connor PG, Chawarski MC, Schottenfeld RS. Treatment of opiate dependence with buprenorphine in primary care. Am J Drug Alcohol Abuse 2002;28:231-241
   CrossRef | Web of Science | Medline