NDARC Technical Report No. 199 (2004)
The Prison Opiate Dependence Treatment Trial (the trial) examined the treatment history and treatment outcomes for 204 heroin users in NSW prisons between January 2002 and January 2004. The trial was commissioned by the New South Wales Corrections Health Service to evaluate the introduction of naltrexone, a long-acting opioid antagonist, through a controlled comparison with the two existing treatments for heroin users: methadone maintenance treatment (MMT) and drug-free counselling (AOD). The randomisation of subjects to each of the three treatment groups was not successful due to a number of factors outside the control of the researchers. Principal among these was the very poor uptake of naltrexone. Only 9 out 66 (14%) subjects assigned to naltrexone actually started naltrexone treatment and ultimately only 14 subjects out of 204 (7%) started naltrexone over the entire two year study period. An intention-to-treat analysis would be inappropriate when so few designated subjects received their experimental treatment. Secondly, the improved availability of MMT and the introduction of the mixed opioid agonist/antagonist buprenorphine meant that experimental control for methadone/buprenorphine was largely lost. Finally, the availability of heroin within NSW prisons declined in line with reduced supply in the general community (Day, Topp et al. 2003). Heroin use was a principal outcome for the study. Low levels of heroin use at baseline considerably reduced the likelihood of detecting any treatment effects. For these reasons the trial ceased recruitment in July 2003 but continued follow up until January 2004.
The trial was successful in recruiting and following up subjects with a 91% follow up achieved. Subjects were assessed for suitability, randomised and interviewed regarding their drug use history, prison history and other health and psychosocial outcomes. Subjects provided hair samples to be tested for opiate use and finger prick blood samples to be tested for HIV and hepatitis C antibodies. The subjects were re-interviewed at six months and provided further hair and blood samples. At twelve months, record checks were undertaken to examine treatment retention, compliance, concomitant medications and side-effects. For analytical purposes, subjects were divided into five mutually exclusive treatment exposure groups. Subjects who received naltrexone prior to their follow up interview were categorised as the naltrexone study group (n=9). Subjects who received buprenorphine were categorised as the buprenorphine group (n=39). Subjects who received MMT only were categorised as the MMT group (n=89). Subjects who received AOD counselling only were categorised as the AOD group (n=23) and finally subjects who did not receive any of these treatment were categorised as a No Treatment group (n=26).
The study found very poor induction and retention rates for oral naltrexone. Only seven percent of all subjects started naltrexone over the two year study period. Among those subjects, only seven percent were retained in treatment at six-months. Six-month retention was significantly lower in the 14 subjects who started naltrexone (7%) compared to the 12 subjects who started methadone (58%) (p=0.0007). Mean days in treatment were 59 (95% CI, 32-86) for naltrexone, 100 (95% CI, 70-130) for buprenorphine and 149 (95% CI, 117-181) for methadone. While compliance to daily doses was good when subjects were receiving naltrexone (98%), most ceased naltrexone once they were released from prison even when specific arrangements were made for community dosing at no cost to the patient. This was of particular concern as overdose risk is highest post-prison release and this may be further increased if subjects have recently ceased naltrexone. No deaths or serious adverse events were noted during the study. Few side effects were noted in those subjects who received naltrexone. Most side effects were minor, including dizziness, nausea, headache, sleep disturbance and loss of appetite which resolved or were manageable. There were no other statistically significant differences in outcomes between the study groups although results were limited by the small sample sizes of the multiple comparison groups.
The experience of this study was consistent with other studies of oral naltrexone in Australia and overseas. The study did not replicate the success observed among prison parolees in the US or work release programs in Singapore. The most likely reason for this was that inmates were not subject to coercion or incentives to enter and stay on naltrexone maintenance. In the absence of such incentives, opioid dependent inmates showed a preference for agonist treatment including methadone maintenance and buprenorphine maintenance. Many inmates who achieved abstinence preferred no treatment or drug free counselling over naltrexone. The overall conclusion of the study was that poor patient acceptability and retention did not support oral naltrexone in this treatment group.
The study also found relatively poor retention in subjects who started buprenorphine (n=21) due to the high proportion (20%) who were discontinued due to diversion. Diverted buprenorphine was the second most injected illicit drug (11%) after heroin (14%) at follow up. Investigation of alternate dose formulations may be warranted. Half the trial subjects did not receive any AOD counselling, mostly because they declined to attend for AOD counselling (42%) or claimed that counselling was not offered (38%). Given that subjects who received AOD counselling had improved outcomes, the underlying reasons for failure to attend or be offered AOD counselling warrant further investigation. Subjects who received no treatment of any kind had the poorest outcomes on most measures. This group was characterised by shorter sentences. New forms of depot preparations and implantable devices for both naltrexone and buprenorphine may overcome the poor treatment retention experienced in this study: however such devices remain experimental. At the conclusion of recruitment for this study, CHS withdrew funding support for oral naltrexone. We conclude from this study that treatment of heroin dependence in correctional settings using oral naltrexone is relatively ineffective because of limited attraction and poor compliance and that compliance is superior for oral methadone which is also more attractive and more effective.
Citation: Shearer, J., Wodak, A. and Dolan, K. (2004) The prison opiate dependence treatment trial, Sydney: National Drug and Alcohol Research Centre.