PEERING OVER THE PARAPET:

A DISCUSSION OF A LOCAL POLICY FOR TREATMENT WITH INJECTABLE METHADONE

Mike Shaw, Clare Brabbins and Sue Ruben, Liverpool Drug Dependency Unit, UK

This paper discusses injectable opiates and their place in the treatment of drug dependency. An overview is given of the debate and controversy surrounding this form of treatment including a historical perspective. The lack of empirical scientific research is discussed and reasons suggested the apparent confusion that prevails. A local policy on the prescription of injectable methadone is presented and discussed as a means of treating opiate -dependent intravenous drug users who continue heavy illicit drug use with its attendant health and social consequences, despite standard treatment with oral methadone. Data are presented on a sample of patients receiving injectable methadone. The results suggest that the local policy is not associated with an adverse effect on HIV risk but is associated with injecting into major veins.

INTRODUCTION

Prescription of injectable opioids is almost exclusively a UK practice. Methadone is the most widely prescribed injectable opioid in the UK, ampoules representing around 10% of all methadone prescriptions (Pilkington, 1996; Strang et al., 1996).

Prescription of methadone ampoules occurs across all areas of practice, comprising 8% of methadone prescriptions issued by general practitioners, 10% of those issued by NHS specialists in drug dependency and 3 3 % of those issued by private clinics (in a recent survey of community pharmacies in England and Wales) (Strang et al., 1996). Despite this there is a lack of robust medical evidence with which to evaluate injectable methadone as an alternative to oral methadone for time- limited or maintenance therapy. There is little information about what may constitute best practice or even current practice for patient selection and management and there is concern that doctors may be prescribing injectable methadone with insufficient specialist expertise or training (Pilkington, 1996).

How has a state of affairs arisen whereby there is widespread use of a form of treatment that is expensive, potentially damaging to health, politically controversial and vulnerable to abuse without there being clear evidence-based recommendations?

The answer is partly to do with historical factors; the UK has a tradition of prescribing a variety of controlled drugs in a number of forms, probably only possible owing to a low initial incidence of opiate dependency in a well-circumscribed sector of the population. Although neither of these factors now applies, the legacy of the 'British System' remains as a wide range of strongly held views amongst practitioners which periodically surface as lively debate and personal criticism (Strang, 1989).

There are schools of thought that advocate wide availability of opiates in whatever form a drug user prefers, including injectables. The rationale behind this is that street drugs will become unprofitable and will disappear along with drug cartels, crime rates will fall and drug users will be able to move on from a 'hand to mouth' existence (Marks, 1987; Brewer et al., 1992).

Critics of this line of reasoning point to the relationship between price and usage of drugs: as street prices fall, usage increases resulting in a greater number of dependent individuals. Also, evidence from legal drugs suggests that instead of disappearing, dealers will focus on the sector of the population for which prescribed injectable opiates would still be unavailable, particularly those under age. Some practitioners go further and are strongly*opposed to prescription of injectable opiates in any form because of the basic philosophical contradiction it presents.

There is general agreement that compared with oral methadone, injectable opiates are more expensive to prescribe and more complex owing to their abuse potential. Advocacy of repeated injection exposes patients to a finite risk to health which must be set against the risks that withholding injectable treatment would present. These clearly amount to case-by-case clinical decisions that are made harder by the lack of scientific evidence (Battersby et al, 1992; Farrell and Strang, 1992).

Trying to make sense of the scientific evidence regarding injectable opiates can prove to be a confusing experience. This is a very difficult area in which to conduct controlled clinical trials but the obstacles have been compounded by studies that have made comparisons between treatments in which the mode of drug delivery has not been the only major factor at variance. The most common additional variables have been the use of differing pharmacological agents (for example comparing oral methadone and injectable heroin) or differing treatment philosophies (for example comparing time-limited injectable treatment with long term oral treatment) or both (Hartnoll et al., 1980; Derks, 1990; Strang et al., 1990). When attempting to appraise 'injectable treatment' it is important to take this heterogeneity into account and recognise that efficacy may vary between injectable treatments.

Choice of drug is probably a major factor in the efficacy of injectable treatment. Short-acting opiates such as heroin and morphine appear inherently unsuitable for the treatment of opiate addiction because frequent dosage is necessary to alleviate withdrawal symptoms. As a result, patients may have difficulty focusing their attention away from drug use and find it harder to achieve a stable lifestyle. This is reflected in studies of patients treated with heroin and morphine in injectable form.

By contrast, methadone has unique pharmacological properties that allow once, or twice daily administration. It has a long half-life due to buffering of plasma levels with a reservoir in non-specific tissue binding sites which only occurs at the relatively high doses that are necessary for opiate-tolerant individuals and prevents withdrawal symptoms for up to 24 hours. This property is retained when methadone is administered intravenously. (jasinski and Preston, 1986; Dole, 1988).

A further important consideration is the philosophy behind injectable treatment once it is offered. Should it be seen as an additional 'carrot' to bring people into treatment who would otherwise remain outside (thereby offering them a degree of harm reduction) or should it form an additional treatment option solely for patients who are already prescribed oral methadone but have not derived sufficient benefit from it?

In this paper we briefly present our local policy for use of injectable methadone, examine the group selected to receive injectable methadone and discuss whether the endorsement of injecting by clinicians adversely affects patients.

THE LIVERPOOL DRUG DEPENDENCY UNIT (LDDU)

At the Liverpool Drug Dependency Unit (LDDU) it is our clinical impression that injectable methadone is a useful treatment for a proportion of patients who are already in treatment but are failing to progress. In determining which patients may benefit there are relative risks that must be taken into account. A particular concern is that providing patients with 'permission' to inject may be associated with adverse
injecting practices and run contrary to the aims of treatment.
The LDDU operates a range of services in Liverpool along broadly based harm-minimisation principles. It is part of the North Mersey Community (NHS) Trust and serves a population of 350 000 from a deprived urban area. The clinic accepts referrals from general practitioners, consultants, any other health care workers or from established agencies that deal with drug problems, including social services, probation and the voluntary sector. When accepting patients into treatment, priority is given to those experiencing severe difficulties. The total number of patients in treatment at the LDDU is 840, 110 of whom are on injectable methadone. All patientsreceive at least monthly follow-up by a designated doctor and nurse in order to review their progress and assess ongoing treatment needs. Patients with particularly complex psychosocial needs receive additional support in the form of home visits from a community psychiatric nurse (30% of patients), access to social workers based within the clinic (20% of patients) or both. Common factors that define cases as complex include psychiatric comorbidity and child welfare issues.
The use of injectable methadone at the LDDU takes the form of a trial of treatment. Once a patient has expressed the desire to be considered for injectable methadone, the decision whether to instigate this treatment is made by the consultant following a multidisciplinary review of the case. The potential risks and benefits of injectable methadone are considered for that individual and selection is based on clinical criteria that can be summarised into ten points:

(1) consultant assessment and subsequent review of t patient; 
(2) patient is reviewed at least monthly;
(3) patient has a long (5 years or more), well established history of daily injecting;
(4) patient requests a trial of injectable methadone;
(5) there has been an adequate trial of oral methadone and the clinical response has beenpoor;
6) the clinical impression is that the patient is motivated to change his/her behaviour;
7) the clinical impression is that prescription of injectable methadone would minimise harm to the patient by reducing the overall frequency of injection and/or by reducing the complications of intravenous 'street' drugs;
8) the trial is terminated if no improvement is made;
9) the trial is terminated if there is clear evidence of non-compliance and/or sale of prescribed drug;
10) a combination of oral and injectable methadone is prescribed whenever possible.

Patients are offered all or part of their daily methadone dose in injectable form if they appear to be tied to the habit of injecting despite a desire to cease illicit drug use ('needle fixation'). Generally such patients have had a trial of oral methadone alone. The continuation of injectable methadone remains subject to multidisciplinary clinical review; a return to oral maintenance is encouraged and is usually implemented by gradual increase in the proportion of oral methadone whilst keeping the total dose constant.

In order to minimise the abuse of prescriptions, treatment with injectable methadone cannot be instigated or continued at the LDDU without ongong clinical review of the patient by the consultant. This policy does not provide 'injectables on demand'; about 30% of patients requesting injectable methadone are not considered suitable.

Study Sample

Patients being prescribed injectable methadone at he time of the study were sampled by using consecutive clinic appointments from I November 1993. Sampling used clinic appointments rather than ctual attendances so that there was no selection bias toward the more stable patients who reliably kept their appointments.

Data Collection

All subjects were given an information sheet and those who consented were interviewed using a structured questionnaire designed for the study. Interviews were conducted by one of the authors and coworkers who had no direct involvement with a patient's care and assurances were given that information would be anonymised and would not influence clinical decisions. Previous studies have shown that users of illicit drugs generally give an accurate report of their behaviour under these circumstances. If a patient declined to participate, this was recorded and some information was obtained from the casenotes to allow comparison between those refusing and the rest of the study group.

Instruments and Data Analysis

Questions relating to HIV risk were taken from the HIV risk-taking behaviour scale which is a valid arid reliable instrument (Darke et al., 198 1 ). Statistical advice and data manipulation were provided by the HIV and drug monitoring department of North West Regional Health Authority.

RESULTS

The study sample comprised 55 patients prescribed injectable methadone, 42 male and 13 female. Ten patients declined to complete questionnaires; refusers did not differ in terms of age, time in treatment or dose.

The group had a mean age of 32.9 years (SD 5.9, range 18-45). Mean age of first drug use was 15.2 years (SD 3.8, range 8-27) and of first injecting drug use was 20.2 years (SD 5. 1, range 13-3 7). Their mean length of time in treatment was 52.1 months (SD37.0, rangeO185). The group received a mean total dose of 66.5mg of methadone (SD 17.7, range 10-100) of which a variable proportion was in injectable form.

Ongoing HIV risk was assessed using the HIV risk questionnaire developed by Darke et al. (199 1). This scale was developed specifically for intravenous drug users and comprises two subscales, one to measure risk from injecting practices and one to measure sexual risk-taking behaviour. There are 11 questions in all, 6 regarding drug use and 5 regarding sexual behaviour; each question contains six alternative responses that are scored according to risk ranging from 0 (low risk) to 5 (high risk). The total score can lie between 0 and 55.

Darke et al. demonstrated this scale to be both valid and reliable. They administered the scale to two groups of injecting drug users who were receiving and awaiting treatment with oral methadone. The treatment group had a mean score of 7.0 (SD 6.4, range 0-30). The nontreatment group had a mean score of 16.3 (SD 6.2, range 2-29).

Our study group returned a mean score of 6.9 (SD 4.2, range 3-20). The HIV scores were also broken down into the two components of sexual behaviour and injecting behaviour to eliminate the possibility that differences in these subscales were cancelling each other out. As this instrument was developed for patients on oral treatment, part of its overall score included total number of 'hits'. Despite the prescription of injectable methadone to patients requiring them to inject on at least one occasion per day, the risk scores were comparable with values obtained by Darke et al. for their treatment group.

Within the group, 5 1 % of patients were using groin as opposed to peripheral sites for injecting. Repeated injecting is the most likely reason for the use of groin sites by our study group, owing to collapse of peripheral veins.

In the past it has been suggested that virtually all intravenous opiate addicts would prefer to be prescribed heroin, particularly in injectable form. In our group, 82% were satisfied with methadone and 80% with the form in which this was taken although 46% did regard their dose of methadone as too low.

DISCUSSION

Our results indicate that this local policy for prescription of injectable methadone to selected unstable patients is not associated with an adverse HIV risk when compared with other work. This study is too limited to be able to make direct comparisons between the efficacy of injectable and oral methadone.

Caution must be taken with any form of injectable treatment and set against the anticipated degree of clinical improvement in health and social functioning. Injectable methadone is more expensive to prescribe than oral methadone and has a higher street value, therefore is more likely to be passed onto the black market. Repeated intravenous injection can be safe given optimal circumstances but in practice may present significant risks, particularly when major veins are used. Conditions of administration are beyond the control of clinicians and it is arguable whether 'permission' to inject remains appropriate once there is evidence of increased risk. Ultimately the decision becomes a clinical one, based on the merits of each case.

We believe we have presented a coherent and explicit local policy for use of injectable methadone. It is our hope that this is a significant first step to promoting debate about the place of injectable methadone in clinical practice and the development of policies that can be applied and evaluated nationally.

Dr Mike Shaw, Liverpool Drug Dependency Unit, Hope House, 26 Rodney Street, Liverpool, UK.

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