The First International Conference On Heroin Maintenance: Research and Evaluation, Nicola Metrebian

Opiate dependency is a major public health and social problem, but whilst oral methadone treatment is the most common form of treatment for opiate dependency and its effectiveness has been well demonstrated, Britain is one of few countries where doctors can legally prescribe pharmaceutical heroin (diamorphine) and injectable methadone.

The practice of prescribing injectable opiates has been part of the British response to opiate dependency, in the case of heroin since the 1920's and in the case of injectable methadone since the 1970's, but the numbers receiving such treatment have always remained small.

Methadone accounts for 96 percent of all opiate prescriptions used for the treatment of drug dependency in the U.K. Although the prescribing of injectable heroin is undertaken on a relatively small scale, accounting for two percent of the total number of prescriptions for opiates, methadone ampulesmake up nine percent, so slightly more, of all methadone prescriptions.

Given the high levels of clinical freedom that we have in the U.K., injectable opiate prescribing, and this includes injectable heroin prescribing, has not been guided by clinical protocols. Rather, it is characterized by a high level of flexibility in treatment eligibility and doses prescribed.

It is argued that oral methadone fails to attract into and retain some opiate dependent users in treatment and that injectable opiate prescribing and heroin prescribing is an attractive treatment option that might offer potential health and social benefits, including reduction in crime and improvements in employment.

However, in the U.K., there is a lack of scientific evidence on which to base these claims, so although we've actually been prescribing injectable heroin for decades, there are very, very few treatment studies. The aim of this treatment was to assess whether prescribing injectable opiates to opiate dependent drug users will result in associated health and social gains.

The design was an observational study of clients attending a London drug treatment clinic between June of 1995 and November 1997; 70 clients were recruited during this time, but this presentation reports on the 58 clients who were followed up at 12 months.

Subjects were allowed to choose the type of treatment they received. Either injectable diamorphine (heroin) or injectable methadone. After a one-month induction period, clients were required to stay with their drug of choice.

The dose was achieved through tolerance testing over a week and stabilization over the first month, after which time there was no change in dosage unless it was reduced. A ceiling dose of 200 milligrams a day of diamorphine or methadone was set. Drugs were dispensed daily at the clinic with weekend take home for the first few weeks, and then at less frequent intervals thereafter.

Clients were not permitted to inject on site, except during their initial tolerance test. To attempt to reduce the risk of diversion, patients or clients had to return their used ampules and the batch numbers were checked before receiving further ampules.

The Australian Opiate Treatment Index was administered to clients at entry and at three-month intervals thereafter. It is a multi-dimensional assessment instrument that measures drug use, crime, health and social functioning.

If we look at the characteristics of the sample of 58 followed up for 12 months, the majority of the sample was male and white. Sixty-four percent chose heroin and 36 percent chose methadone. They had a median age of 38 years and a median length of injecting use of 19.5 years with a median of four times previously in an opiate treatment. All were current injectors.

Eighty-six percent, (50), were still in treatment after three months follow-up. And 69 percent were still in treatment after six months follow-up. And 57 percent were in treatment after 12 months. Most drop outs were disciplinary and related to violation of study protocol; 25 percent defaulted, 16 percent were moved to oral methadone for health reasons, eight percent requested a move to oral methadone, eight percent went to prison for drug related offenses and one left to become abstinent and one died. This was not an overdose.

A higher mean dose of heroin was prescribed than methadone over three and 12 months. The mean dose of heroin at three months was 181 milligrams a day versus 148 for injectable methadone, and at 12 months, 185 versus 161.

The majority of those prescribed heroin, that's 71 percent reported experiencing nighttime withdrawals due to heroin's shorter duration of action, and were thus given an additional prescription of oral methadone.

Significant reductions were found in the proportion of clients reporting using all the different drug classes over three months with the exception of amphetamines which reduced, but the numbers were too small to reach significance, and are not shown here. These reductions were generally sustained between three and 12 months.

Alcohol use increases and then drops. When we look at the amount of standardized units (as we measure it in the U.K.) the amount consumed reduced over 12 months.

This table shows a proportion of clients reporting engaging in any criminal activity at entry, three, six and 12 months. At three months there's a large reduction in crime and this is sustained between three and 12 months.

This table shows the mean OTI score for social functioning, health and psychological adjustment. Improvements in any domains are indicated by a reduction in the score. At three months, social functioning, that's employment, housing, relationships and involvement in drug using networks, health status and psychological adjustment, had all significantly improved. And these improvements were sustained between three and 12 months.

Now, at three months, although not significant, levels of HIV risk behavior, that's injecting and sexual risk behavior reduced, the OTI, (the instrument used) considers any injecting as risk behavior. Sexual risk behavior reduced slightly.

Illicit drug injecting risk behavior, (frequency of injecting and sharing of illicit drugs) reduced significantly, and these reductions were generally sustained.

If we look at the type of injectable opiate received separately, we find that the heroin group have a significantly greater reduction in their use of illicit heroin over three months than the methadone group, than those who chose and were receiving injectable methadone. However, the heroin group was using larger amounts of illicit heroin at entry and therefore had a greater potential to change. No other significant differences were found between the two groups, so it made little difference whether people chose injectable methadone or injectable heroin.

To conclude, findings suggest that opiate dependent drug users with long injecting careers -- most started injecting between 1970 and 1982 -- and multiple failed opiate treatment experiences have been attracted into and retained by prescribing injectable opiates, including injectable heroin.

Compared to drug users recruited in a U.K. national study of oral methadone maintenance programs, our clients were older -- 38 years versus their 29 years -- and had been injecting for longer -- 19.5 years versus nine years for the oral methadone.

While some clinicians and drug users forums perceive a high demand for heroin prescribing, our findings suggest that it is not always the preferred drug of choice, with over one third choosing injectable methadone. Now, 86 percent were still in treatment at three months, 69 percent at six months and 57 percent at 12 months. While the retention rate was higher than that reported by, again, a U.K. national study of oral methadone maintenance programs at one month, and similar at six months. And this suggests that long term opiate dependent drug users were well retained in treatment. Other U.K. studies have found very similar levels of retention.

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. It is impossible to know whether these study clients would have been more likely to move towards abstinence had they received oral methadone. However, these clients were long term opiate dependent drug users with a median of four previous opiate treatments and had tried and failed at least two oral methadone treatments without achieving abstinence.

Now, this group of problematic drug users made significant health and social gains, and reduced drug related harm in the first three months. These gains were generally sustained between three and 12 months. And there were no differences in health and social status at entry of those discharged from treatment and no differences in outcome between those choosing injectable methadone and those choosing heroin.

There has been some concern that clients' health might deteriorate whilst receiving prescribed injectable drugs. And previous U.K. research has shown little improvements in health and social well-being. But in contrast, this study has found that while some clients were injecting into their femoral vein, two moved to oral methadone due to poor health related to injecting and one died. For those remaining in treatment, significant health and social improvements were made. And these improvements were sustained between three, six and 12 months, as was reduction in illicit drug injecting risk behavior.

Therefore, the problems of maintaining good health care need to weighed up against the ability that prescribing injectable opiates has for client attraction and retention, and thus for providing clean pharmaceutical drugs and injecting equipment, advice in safer injecting practices and health care.

The suggestion that prescribing injectable opiates eliminates illicit drug use and criminal activity has not been supported. Whilst illicit drug use and criminal activity reduced, neither was eliminated, and again, similar results were obtained by other U.K. studies.

Diversion of prescribed drugs is obviously of particular concern where there is no observed on-site injecting. Now, whilst the clinic attempted to reduce the risk of diversion, ways to identify the presence or absence of illicit and prescribed heroin are needed to corroborate self-reporting of illicit drug use and compliance with prescription.

Injectable opiate prescribing is one of many options in a range of prescribing modalities in the U.K., and our findings endorse the view that this option is feasible. We have shown it attracts and retains long term resistant opiate dependent drug users in treatment and is associated with significant and sustained reductions in drug use and improvements in health and social status.

However, further research is needed to examine the potential benefits of this treatment at both and individual and a community level. We are in the process of designing a multi-center national heroin trial to assess the economic benefits of prescribing injectable heroin and injectable methadone.

Selected questions and answers:

Question: If you give over 80 milligrams of methadone a day, over a period of a month, they will develop a tolerance using methadone itself. Now, what are they getting from the injectable methadone?

NICOLA METREBIAN: People weren't increasing their tolerance. People were staying on similar levels of injectable methadone.

WIM VAN DEN BRINK, MD, PHD: Did they go on using the oral methadone?

NICOLA METREBIAN: No, they didn't use oral methadone. They were only given injectable methadone. People who were prescribed injectable methadone were only given injectable methadone they had no oral methadone.

NICOLA METREBIAN: Some people reported that they did get a hit off having that amount of injectable methadone but most of them said they didn't, and all it did was keep them stable.

MAN: That's right, so why don't they go to oral methadone?

NICOLA METREBIAN: Because they chose to carry on injecting, that's what they wanted. They refused to have oral methadone, and this is why we gave them a choice, to see whether people would, in fact, all choose injectable heroin. Their reasons for choosing injectable methadone were that they wanted to be kept on an even keel. And secondly, that they only had to inject themselves once not three or four times a day. But they felt they couldn't cope with only having oral methadone.

MAN: I was wondering because you gave people take home if you looked at police intervention or police harassment [UNINTEL - PHRASE] program and how that enabled people to continue the trial protocol.

NICOLA METREBIAN: The police were very supportive of the program. In the U.K., it's very different to the U.S. because many of the police are extremely supportive of having a heroin program because they believe that it is going to reduce crime.

In terms of locally around the clinic, we didn't have a problem there. In the U.K., people are quite used to people taking their oral methadone home, although we do have on site dispensing as well. But there were no related problems between the clinic and the police. There were a couple of problems with people either losing their amps or leaving them somewhere, but not with police harassment. And we involved the police in the local community as well, so they were very aware of this program.

WIM VAN DEN BRINK, MD, PHD: I have three more questions and then we have to finish.

MAN: My question is you said that people were injecting heroin and using methadone orally.

NICOLA METREBIAN: For the majority of them, yes. There were a number of clients who continued only to use heroin, they didn't ask for oral methadone. I know in the other studies, oral methadone is being given with injectable heroin, and we found out that that's what we would have to do because so many people requested it.

What they said to us was that it was during the night that they would start going into withdrawal, and so they wanted some oral methadone to tide them over.

MAN: Ninety-six percent of the people were on methadone in the U.K.?

NICOLA METREBIAN: It's 96 percent of all opiate prescriptions are for the methadone.

MAN: Oral and injectable? How do you divide that?

NICOLA METREBIAN: The figure is for methadone. And then nine percent.

MAN: Ninety?

NICOLA METREBIAN: Nine.

MAN: Nine.

NICOLA METREBIAN: Nine is injectable methadone.

NICOLA METREBIAN: At the beginning of the study, we decided to have a ceiling level. The clinicians in the study felt that because 80 milligrams of oral methadone was recommended, that they would choose to have 200 milligrams as a ceiling level for injectable heroin and in fact it was decided to have injectable methadone at that level too.

I think probably the heroin should be higher than the methadone. And also, I would like to add that there was no supervised injecting on site. And so the organizers were very aware that they had to be very careful about diversion.

NICOLA METREBIAN: The injectable program was very similar to the oral methadone programs that are in the U.K. Saying that, that's fairly meaningless, really, because there are so many different types, some of which we call structured and some of which wouldn't fall into that category.

So in the U.K., there's a whole range of ways oral methadone is delivered, and some people get oral methadone with very basic psychosocial interventions, others are in much more formal structured programs where they have very specific psychosocial interventions and they move through phases and eventually hopefully get maintained by GP's in the community.

In the injectable clinic clients were seen regularly by their what we call key worker, a nurse. They would have one assigned to them and they would see them for counseling for half an hour once a week for the first couple of months and then it was at less frequent intervals thereafter. They saw the doctor and as needed were referred to a psychologist or a social worker, or occupational therapist. Motivational interviewing and relapse prevention were conducted mainly by their key workers rather than in groups.

NICOLA METREBIAN: For us in Britain this is a particularly important issue because there's no on site supervised injecting, and so two things that we would be most interested in monitoring. One is illicit street heroin use and the other is prescribed heroin use. Diversion as well as compliance with consumption.

And work has been going on to find a way to monitor illicit heroin use in those prescribed pharmaceutical heroin. Codeine may well be a good marker for street heroin. The problem is, putting a marker in the prescribed heroin is very, very expensive and we're on such a terribly limited budget that we can't actually afford to do that at the moment.