20 March 2009

Does adding an antagonist reduce injecting?

Lack of Reduction in Buprenorphine Injection After Introduction of Co-Formulated Buprenorphine/Naloxone to the Malaysian Market. Bruce RD, Govindasamy S, Sylla L, Kamarulzaman A, Altice FL. Am J Drug Alcohol Abuse 2009 Feb 12:1

Dear Colleagues,

In this important paper Dr Bruce from Yale University finds no reduction in quantities injected after the widespread change from pure to combination product (Suboxone). Even more worrying is a finding of increased needle sharing in the high proportion who reported withdrawal symptoms following the change.

In a group of 41 recruited illicit buprenorphine injectors in Kuala Lumpur, Bruce and co-workers posed questions about injection of both the pure and combination products after a change in Government policy aimed at discouraging injecting. Pure buprenorphine was banned due to widespread abuse (as it was in New Zealand in 1991) and replaced with a combination product containing naloxone. As in previous experiences, (Robinson 1993), a change to the combination product was not associated with elimination or substantial reduction in abuse.

Half the sample (20) reported experiencing withdrawal symptoms after the change yet this had apparently not discouraged them from injecting. Average daily use increased 30% (from 1.9 to 2.5mg per day). Reported needle sharing was much more prevalent in those who also reported withdrawal symptoms (15 out of 20 or 75% of the ‘withdrawal’ subgroup).

The 41 used other drugs such as methadone (4), ketamine (10), amphetamine (6) or benzodiazepines (13). The authors speculate that this may have been to medicate withdrawals in some cases. They state that none of the subjects appeared to be using the buprenorphine as a recreational drug but to maintain a functional level of opiates in the body.

This paper is not consistent with claims that Suboxone reduces injecting behaviour. While the manufacturer has always been modest in its claims, others have made extravagant statements about the alleged property of combination buprenorphine to prevent diversion. It appears that the drug was approved by the American FDA and marketed without rigorous comparative studies. Combination agonist/antagonists may sound persuasive in theory but this has never been demonstrated in the field despite a long pedigree (methadone and naloxone were first tried together over 30 years ago). Now, 15 years apart and in very different settings, two naturalistic studies on buprenorphine make comparable and consistent findings.

Like Bruce in Malaysia, Robinson in New Zealand took advantage of a similar scenario in which buprenorphine was being widely abused in the community. The government and manufacturer changed to the naloxone-containing product, so Robinson was able to interview patients enrolling in his opioid treatment program in Wellington, NZ. He reported numerous demographic and drug use characteristics before and after, finding that the drug was still widely abused. Indeed, for 59% it was still the drug of choice - and mostly injected.

Interestingly, the Malaysian figures are remarkably close to a published comparison of pure buprenorphine with the combination product. In a small pilot study, Bell and colleagues found that substantial increases (average 50%) in doses were needed by nearly all 17 stable subjects after changing from Subutex to Suboxone. Another factor I learned in my research was that apparently the main driver for injecting in Malaysia was financial since sublingual administration requires a far higher dose due to lower bio-availability and all doses must be paid for by the patient in that country.

Comments by Andrew Byrne ..

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Robinson GM, Dukes PD, Robinson BJ, Cooke RR, Mahoney GN. The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Dependence (1993) 33;1:81-6
Bell J, Byron G, Gibson A, Morris A. A pilot study of buprenorphine-naloxone combination tablet (Suboxone®) in treatment of opioid dependence. Drug Alcohol Rev (2004) 23;3:311-318