Feasibility of prescribing injectable heroin and methadone to opiate-dependent drug users: associated health gains and harm reductions

Abstract

Introduction

Despite the legality of this practice, numbers of patients receiving such treatment remain small. Methadone accounts for 96% of all opiate prescriptions for treating drug dependency in the United Kingdom;³ injectable heroin accounts for only 2% of the total number of prescriptions for opiates;⁴ and methadone ampoules make up 9% of all methadone prescriptions.³ While injectable methadone is prescribed by doctors attached to specialist drug services, general practitioners and private doctors, a special licence from the Home Office is required to prescribe injectable heroin, and most doctors with such licences work in specialist drug services.⁵ Injectable opiate prescribing has not been guided by clinical protocols, but has been characterised by a high level of flexibility in decisions about eligible patients and dosage.

The prescribing of injectable opiates has been the source of international controversy and debate. A large research trial has been undertaken in Switzerland⁶ and, in Australia, a heroin trial was designed to determine the impact of offering the choice of an injectable opiate prescription.⁷ However, the Australian Federal Government has decided that this trial will not proceed.

It has been argued that injectable opiate prescribing may attract resistant opiate-dependent users into, and retain them in, treatment, with potential health and social benefits, including a reduction in crime,⁸ but there is a lack of scientific evidence on which to base these claims. The Swiss trial found that heroin prescribing retained drug users in treatment, with reductions in crime and improvements in health status.⁶ However, results of the most influential research carried out in the UK -- a randomised controlled trial comparing maintenance with oral methadone with heroin -- were inconclusive.⁹ In that study, the heroin group were better retained in treatment, but they continued to inject regularly and use illicit opiates in small amounts, which could lead to increasing clinic caseloads. On the other hand, the oral methadone group were more likely to either drop out of treatment or become abstinent. There were higher arrest rates and higher levels of drug involvement and criminal activity among those who did not become abstinent. Other studies have also found conflicting results.^10-12

In this study we aimed to assess the feasibility of offering opiate-dependent injecting drug users the choice of treatment with injectable heroin (diamorphine) or injectable methadone, and to examine possible health and social gains associated with prescribing injectable opiates.  

Methods

Eligible patients met the following criteria: aged over 21 years; dependent on opiates; unable or unwilling to give up injecting (defined by injecting for a minimum of three years with consistent injecting over the previous nine months and evidence of injecting over the past three months); previously failing oral methadone treatment (defined by regular continued use of illicit opiates while receiving oral methadone, continuing to inject regularly and receiving doses of oral methadone in excess of 80 mg/day); and problems relating to drug use in areas of health, social functioning or crime.

Patients chose treatment with either injectable diamorphine (heroin) or injectable methadone. After a one-month induction period, they were required to stay with their drug of choice. A ceiling dose of 200 mg/day of either drug was set, and the treatment dose was achieved through tolerance testing over one week and stabilisation over the first month; after this time doses could only be reduced. Drugs were dispensed at the clinic daily (Monday to Friday with weekend doses taken home) for the first few weeks and then less frequently (a few times a week or weekly). After their initial tolerance test, patients were not permitted to inject on-site. To reduce the risk of injectable opiates being diverted to others, patients had to return used ampoules (batch numbers were checked) before receiving further ampoules.

Criteria for disciplinary discharge from the study were evidence of "double-scripting" (receiving an additional prescription for opiates for drug dependency outside the clinic), dealing in the injectable opiates prescribed in this study, violence in the clinic, continual and persistent evidence of illicit drug use, consistently failing to return used ampoules, and injecting outside the clinic in the hospital grounds.

The Australian Opiate Treatment Index (OTI)¹³ -- a multidimensional scale measuring illicit drug use, HIV risk behaviour, criminal activity, social functioning, physical and psychological health -- was administered to patients at entry and at three-monthly intervals. This instrument, which has been validated in both Australia¹³ and the UK,¹⁴ has a high correlation with doctors' and nurses' reports and with urine results at opiate treatment settings.¹⁴

Clinic doctors used standardised instruments to rate patients' health and psychological well-being at entry and at three-monthly intervals. These instruments included a physical rating scale for recording doctors' opinions of patients' physical health, including cardiovascular, respiratory, gastrointestinal, central nervous system and injecting-related health (Tallack F, Metrebian N, The Centre for Research on Drugs and Health Behaviour, London, 1996), and the Brief Psychiatric Rating Scale¹⁵ for recording doctors' judgements of patients' psychopathology. In addition, illicit drug use was measured through random urine tests throughout the treatment.

Statistical analysis

Tests of significance included t tests for related samples, and McNemar's chi-squared tests for dichotomous and ordinal data. Results from parametric and non-parametric tests were compared where normal approximations to the underlying distributions were suspect. We considered a P value of 0.05 to be significant.  

Results

Thirty-seven (64%) chose to receive diamorphine, 21 (36%) chose methadone. A higher mean dose of diamorphine was prescribed over three months (diamorphine, 181.43 mg/day [SD, 22.2; range, 120-200] v. methadone, 148.18 mg/day [SD, 45.1; range, 100-200) and over 12 months (185.24 mg/day [SD, 15.7; range, 150-200 v. 161.25 mg/day [SD, 46.4; range, 90-200]). Fifteen of the patients prescribed heroin (71%) reported experiencing night-time withdrawal symptoms as a result of heroin's shorter duration of action and were thus given an additional prescription for oral methadone. The mean dose of additional oral methadone was 24 mg/day (SD, 5.2; range, 20-30). A number of patients were found loitering in the vicinity of the clinic after their prescriptions were dispensed, and one was found injecting the prescription while still on hospital premises. No other major postdispensing problems were reported in the surrounding community.

Fifty patients (86%) were still in treatment after three months, 40 (69%) after six months and 33 (57%) after 12 months. Reasons for discontinuing treatment are given in Box 1.

Patients still in treatment at three months had significantly reduced their consumption of illicit drugs (with the exception of amphetamines, which did reduce, but not significantly), and made positive changes in all health and social domains. Self-reported criminal behaviour was initially low and further significantly reduced. There were significant improvements in social functioning (employment, housing, relationships and involvement in drug-using networks), health status and psychological adjustment. HIV risk behaviour (injecting and sexual risk behaviour -- the OTI considers any injecting as risk behaviour), and illicit drug-injecting risk behaviour (frequency of injecting and sharing of illicit drugs) reduced significantly. Although not significant, levels of sexual risk behaviour reduced slightly.

There were no significant differences in measures of health and social behaviour between three and six months (data not shown), except for illicit drug injecting, which increased, although at six months it was still significantly less than at entry (1.13 [SD, 2.06] v. 5.66 [SD, 4.11]; P < 0.0001).

Between six and 12 months, there were significant reductions in HIV risk behaviour, illicit drug-injecting risk behaviour and sexual risk behaviour, but no other significant changes.

Results of urinalysis suggest that there were (non-significant) reductions in tranquilliser, amphetamine, and cocaine use between entry and three months, and between three and six months, which were sustained between three and 12 months. Few patients receiving injectable methadone were using illicit opiates. Measures of health and psychological status as reported by clinic doctors suggest health and psychological well-being had significantly improved at three months and these improvements were generally sustained. These findings were similar to measures of self-report.

All measures reported at six and 12 months had significantly improved or reduced compared with measures obtained for the same sample at entry, with the exception of HIV risk, sexual risk and doctors' rating of psychological well-being, which had not significantly reduced or improved at six months but did reach significance again at 12 months. There were no differences found in drug use, health or social status reported at entry between those leaving treatment before 12 months and those remaining.  

Discussion

While some clinicians¹⁷ and drug users' forums perceive a high demand for heroin treatment, our findings suggest that heroin is not always the drug chosen by users, with over one-third choosing injectable methadone. There has been much discussion about the correct dose of heroin.¹⁸ Over 12 months doses remained within the limit of 200 mg/day. In the Swiss study patients were stabilised on much higher doses of 500-600 mg/day.¹⁹

While interpretation of our findings is limited by the absence of a control group receiving oral methadone therapy and by reliance on self-report data, this is one of few studies to systematically examine the use of injectable opiates in treating opiate dependence, and the results will be used to inform a multicentre randomised controlled trial.

In our study, at six months, 31% of patients had left treatment, and 40% of the 25 who left over the full 12 months were discharged because they violated the study protocol. Only two (16%) requested a move to oral methadone therapy and one became abstinent. There was one fatality (from hepatic failure) but no overdoses. By comparison, in the Swiss study of 366 patients receiving injectable heroin,²⁰ 18% had left treatment at six months and, of these, 48% switched to another treatment modality (mostly methadone maintenance) and 25% were excluded for threat of violence or other inappropriate behaviour. Four died and there were no overdoses.

The retention rate in our study was higher than that reported by a national study of oral methadone maintenance programs at one month¹⁵ (86% v. 78%), and similar at six months (69% v. 67%).²¹ This suggests that the long-term opiate-dependent drug users in our study were well retained in treatment. Other studies have found similar high retention levels.^9-11

There are concerns that prescribing injectable opiates might encourage drug users to continue injecting and discourage them from accepting oral methadone treatment or becoming abstinent.⁹ It is impossible to know whether our patients would have been more likely to move towards abstinence had they received oral methadone. However, these patients were long-term opiate-dependent drug users who had had a median of four previous opiate treatments and had tried and failed at least two oral methadone treatments without achieving abstinence.

Our patients made significant health and social gains and experienced significantly reduced drug-related harm in the first three months. These gains were generally sustained between three and six, and six and 12 months. At entry, there were no significant differences in health and social status between patients later discharged from treatment and those who remained in the study.

There has been some concern that patients' health might deteriorate while receiving prescribed injectable drugs.¹⁰ Previous research has shown little improvement in health and social wellbeing.^9-11 The study by Battersby et al¹⁰ of drug users at high risk from serious physical illness, including HIV, found one individual developed a life-threatening illness (cervical spine osteomyelitis resulting from intravenous drug use) but survived, several injected into their femoral vein (a highly dangerous practice which carries a high risk of causing deep venous thromboses) and the health of 20% deteriorated. However, the authors concluded that "it was not possible to determine the nature of risk taking that would have occurred ... in the absence of the present treatment intervention". By contrast, we found that, although some patients were also injecting into their femoral vein, two moved to oral methadone because of poor health related to injecting and one died, for those remaining in treatment significant improvements were made in health, psychological adjustment and social functioning. These improvements were seen between entry and three months, and sustained between three, six and 12 months. There was also a reduction in illicit drug-injecting risk behaviour. Doctors' ratings of patients' health and psychological well-being verified these improvements. The problems of vein care associated with injectable opiates need to be weighed up against benefits in client attraction and retention, and in the provision of clean pharmaceutical drugs and injecting equipment, and advice on safer injecting practices and healthcare.

Our findings do not support the suggestion that prescribing injectable opiates eliminates illicit drug use and criminal activity,^22-24 as both declined significantly, but neither was eliminated. Similar results have been obtained by other studies.^9-11 Results of urinalysis corroborated self-reported non-opiate drug use. However, it was not possible to corroborate self-reported opiate use as we could not differentiate between illicit and prescribed heroin.

Diversion of prescribed opiates to others is of particular concern when there is no observed on-site injecting. While the clinic attempted to reduce the risk of such diversion, ways of corroborating self-reported compliance with prescription and illicit opiate use are needed.

Prescribing injectable opiates is one of many options in a range of treatments for opiate-dependent drug users. In showing that it attracts and retains long term resistant opiate-dependent drug users in treatment and that it is associated with significant and sustained reductions in drug use and improvements in health and social status, our findings endorse the view that it is a feasible option. Further research is needed to examine the potential benefits of this treatment at both an individual and community level. Randomised controlled trials comparing alternative treatments and their relative cost effectiveness are required to fully assess this treatment option.  

Acknowledgements

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