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To the Editor: Because buprenorphine has only partial opioid agonist activity and thus has a lower risk of overdose,¹ it may be an alternative to methadone in the treatment of heroin dependence. Buprenorphine has been used for this purpose in France, where general practitioners have been permitted to prescribe it since 1996 with less monitoring than methadone, which is available only in specialized treatment centers.² Buprenorphine thus has theoretically more risk of adverse effects and increased diversion than methadone. We computed the death rate from overdose of buprenorphine and methadone in France from 1994 to 1998.

Methods
All sudden deaths in France that are thought to be due to use of an illegal substance or misuse of a legal substance are reported to a centralized agency (Office pour la Répression du Trafic Illicite des Stupefiants). Overdose deaths are defined in this database as illicit use of a substance whether such a substance is illegal (eg, heroin) or legal (eg, prescription medication) but diverted from its normal treatment setting. The causes of such deaths are determined based on on-site evidence and not by laboratory results.

After tabulating the number of deaths attributed to buprenorphine or methadone from 1994 to 1998, we estimated the number of French patients who received either buprenorphine or methadone by dividing the quantity of medication sold in France by the average estimated daily dose.³ Determination of average daily dose was based on surveys among patients in treatment,^3-6 and the quantity sold was made available by the manufacturers through government agencies.

Results
From 1994 to 1998 there were an estimated 1.4 times more buprenorphine-related deaths than methadone-related deaths in France (Table 1). However, 14 times more patients received buprenorphine than methadone. The yearly estimated death rate related to methadone use was at least 3 times greater than the death rate related to buprenorphine use. If all patients in France who received either of these drugs had been treated only with methadone, the expected number of deaths would have been 288 instead of 46.

View this table: [in this window] [in a new window] Table. Deaths Attributable to Methadone vs Buprenorphine in France, 1994-1998

Comment
There are several sources of possible inaccuracy in these data, including biases in determination of cause of death and recording. However, we think that such influences would not differentially effect estimates of methadone vs buprenorphine death rates. The large effect size in this population-based estimate suggests that buprenorphine is a safe alternative to methadone, even when prescribed under conditions of increased ease of access.

Marc Auriacombe, MD,MSc; Pascale Franques, MD,MPh; Jean Tignol, MD
Groupe d'Étude des Addictions
Laboratoire de Psychiatrie
Université Victor Segalen
Bordeaux, France

1. Lewis JW. Buprenorphine. New York, NY: Wiley-Liss; 1995. 2. Auriacombe M. Overview of substitution treatment for heroin users in France. In: Farrell M, Howes S, Verster A, Davoli M, eds. Reviewing Current Practice in Drug Substitution Treatment in Europe. Lisbon, Portugal: EMCDDA; 1999:61-68. 3. Lert F, Puech A, Begaud B, et al. Evaluer la mise à disposition du Subutex pour la prise en charge des usagers de drogue. Paris, France: INSERM; 1998. 4. Auriacombe M, Franques P, Bertorelle V, Tignol J. Use of buprenorphine for substitution treatment: a French experience in Bordeaux and Bayonne. Res Clin Forum. 1997;19:47-50. 5. Auriacombe M, Tignol J. Buprenorphine use in France: quality of life and conditions for treatment success. Res Clin Forum. 1997;19:25-32. 6. Tignol J, Daulouède J, Auriacombe M, de Ducla M. Utilisation de la méthadone et de la buprénorphine pour le traitement des toxicomanes aux opiacés en médecine de ville. Perspect Psychiatriques. 1998;37:370-378.

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2001;285:45.

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