Drug-related hospital morbidity following heroin dependence treatment with methadone or naltrexone implantation

Arch Gen Psychiatry 2008;65(4):457-465.

This trial, published in the Archives of General Psychiatry, sought to evaluate the longer-term effects of heroin dependence treatment on patient’s drug use and associated hospital morbidity. The authors note that the focus of research in this area has been on shorter-term changes and health effects, and this study was carried out to address this lack of data. They compared two treatments: methadone maintenance treatment (MMT) and naltrexone implants. Although MMT has been widely studied and shown to be of benefit, the abuse of other drugs in those on treatment has not been studied and there have been concerns that it enables the co-use of illicit opioids. Naltrexone (opioid antagonist) implants were developed in an attempt to overcome the non-compliance seen with the oral version; however there is concern that users will adopt new non-opioid drugs as a substitute for heroin.

The study was a retrospective longitudinal follow-up, using data collected prospectively via a hospital reporting system in Perth to identify patients receiving initial treatment for heroin dependence with either MMT (n=522) or a naltrexone implant (n=314) between January 1 2001 and December 30 2002. All drug-related hospital morbidities recorded during the 6 months pre-treatment and 3.5 years post-treatment were recorded.

The main findings were as follows:

• Following naltrexone implant treatment (NIT), the risk of opioid-related overdose at 3.5 years was reduced (OR 0.23; 95% CI 0.11-0.48) and there was evidence for a decreased risk with increasing age (OR 0.31 [95% CI, 0.15-0.68] for a 35-year-old patient versus a 25-year-old match. No statistically significant effect of MMT on this endpoint was observed at either 6 months or three years.
• NIT was associated with a reduction in the risk for other opioid-related hospitalizations after 3.5 years (OR, 0.64; 95% CI, 0.46-0.89). No significant changes for this outcome were observed for patients in the MMT group.
• In the shorter term (6 months), the risk of non-opioid overdoses was statistically significantly increased in older patients (aged 35 years) receiving either treatment (OR of 5.03 [95% CI, 1.18-21.54] for those receiving MMT and OR of 16.31 [95% CI, 3.07-86.53] for those receiving NIT. There was no change in younger patients and no statistically significant effects for either treatment were seen at 3.5 years.
• NIT was associated with an increased risk of other non-opioid related hospitalizations (e.g. dependence and withdrawal) at 3.5 years (OR of 1.52; 95% CI 1.04-2.23). The risk appeared to remain constant however in those receiving MMT.
• There were 6 drug-related deaths: 5 after MMT and 1 after naltrexone implantation.

The authors conclude that "naltrexone implants, but not methadone maintenance, has long-term benefits in reducing opioid-related hospital morbidity. However, long-lasting and increased non-opioid drug–related morbidity following naltrexone implantation is particularly concerning. Similar studies are required to confirm these findings".