Unplanned admissions to two Sydney public hospitals after naltrexone implants
Author: Colin L Brewer
Published online: 20 October 2008
To the Editor: A recent article by Lintzeris and colleagues,1 ostensibly about naltrexone implants, actually has little to do with implant treatment. Only one of the 12 reported cases involved problems linked specifically to naltrexone (antagonist) treatment being administered in implanted rather than oral form. This case involved infection at the implant site — undesirable, certainly, but about as noteworthy as the occasional infections that occur after abdominal surgery or breast implantation, despite antibiotic prophylaxis and careful technique. The remaining 11 admissions reflected not implant use but either the procedure of rapid antagonist induction (RAI) or the desired pharmacological effects for which naltrexone was prescribed in the first place (and one admission for unrelated pneumonia).
RAI is needed because conventional antagonist induction requires complete opiate withdrawal before starting naltrexone. As true conventional withdrawal completion rates, even with inpatients, are typically below 30%,2 conventional techniques will typically achieve only derisory naltrexone induction rates. Various forms of RAI or accelerated induction, with induction rates typically around 100%, are more effective and more cost-effective.3,4 Similarly, complaining that pain management is difficult in naltrexone patients is like complaining that patients being treated with anticoagulants bleed or bruise more after surgery or injury. Fortunately, effective non-opiates (notably subanaesthetic ketamine) exist.
The acute post-RAI problems seen in this case series would have been identical had every patient undergone RAI to oral rather than implanted naltrexone. Indeed, while 150 mg orally could block opiate analgesia for up to 72 hours, implants produce low but consistently effective naltrexone levels, disappearing within hours of implant removal, should that be unavoidable. I agree, however, that RAI clinics should optimise immediate post-RAI management.
A recent conference featured the first presentations of the first four randomised controlled trials of implanted naltrexone. Three showed statistically and (more importantly) clinically significant advantages over “as usual” post-withdrawal treatment,5 or over oral naltrexone and placebo implants.6,7 The fourth,8 comparing implants with methadone maintenance in pre-release prisoners, had only modest statistical power (n = 21), but implant patients had less dropout and used about 50% less heroin. We already know that long-acting implants can largely prevent the opioid overdoses that are otherwise an intrinsic and sometimes lethal hazard of all abstinence-based programs;9 and that all implants prevent the otherwise high relapse rates typical of the first 4–6 weeks after detoxification.10
Surgeons, I am shocked to discover, have been using anaesthesia for 162 years without a comparable placebo-controlled evidence base.
Competing interests
References
- Lintzeris N, Lee S, Scopelliti L, et al. Unplanned admissions to two Sydney public hospitals after naltrexone implants. Med J Aust 2008; 188: 441-444.
- Strang J, McCambridge J, Best D, et al. Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study. BMJ 2003; 326: 959-960. 0_i1091851
- Laheij RJF, Krabbe PFM, De Jong CAJ. Rapid heroin detoxification under general anesthesia [letter]. JAMA 2000; 283: 1143. 0_CBBFHIHH
- Currie J, Collins L, Mudaliar Y, et al. Rapid induction onto naltrexone: a randomised clinical trial of anesthesia-assisted versus sedation-assisted techniques, and a comparison with conventional opiate detoxification. Report to the Government of New South Wales. Sydney: Western Sydney Area Health Service Drug and Alcohol Service, 2000. 0_i1091855
- Kunøe N, Lobmaier PP, Waal H. A randomized prospective trial of naltrexone implants for opioid dependence [abstract]. The 9th Stapleford International Addiction Conference; 2008 May 23–26; Athens, Greece. http://www.stapleford-athens.net (accessed Aug 2008).
- Krupitsky E, Zvartau E, Egorova V, et al. A double-blind, placebo controlled randomized clinical trial of long acting implantable formulation of naltrexone for heroin dependence: results of interim analysis [abstract]. The 9th Stapleford International Addiction Conference; 2008 May 23–26; Athens, Greece. http://www.stapleford-athens.net (accessed Aug 2008).
- Hulse GK, Low V, Stalenberg V, et al. Tissue compatability, biodegradability, blood naltrexone levels, and heroin overdose following treatment of heroin dependent persons with sustained release naltrexone-poly(dl-lactide) implants. (Study 5: Randomised double-blind placebo controlled clinical trial compared to oral naltrexone.) [abstract]. The 9th Stapleford International Addiction Conference; 2008 May 23–26; Athens, Greece. http://www.stapleford-athens.net (accessed Aug 2008).
- Lobmaier P, Kunøe N, Waal H. Naltrexone implants compared to methadone maintenance treatment for opioid dependence among pre-release inmates [abstract]. The 9th Stapleford International Addiction Conference; 2008 May 23–26; Athens, Greece. http://www.stapleford-athens.net (accessed Aug 2008).
- Hulse GK, Tait RJ, Comer SD, et al. Reducing hospital presentations for opioid overdose in patients treated with sustained release naltrexone implants. Drug Alcohol Depend 2005; 79: 351-357. 0_i1091865
- Brewer C. Response to Degenhardt et al: “depot naltrexone use for opioid dependence in Australia: large-scale use of an unregistered medication in the absence of data on safety and efficacy”. Drug Alcohol Rev 2008; 27: 447-448. 0_i1091869