Papers

RANDOMISED TRIAL OF HEROIN MAINTENANCE PROGRAMME FOR ADDICTS WHO FAIL IN
CONVENTIONAL DRUG TREATMENTS

Thomas V Perneger, medical epidemiologist, a Francisco Giner, resident, b
Miguel del Rio, fellow, b Annie Mino, head of division. b

a Institute of Social and Preventive Medicine, University of Geneva Medical
School, CH-1211 Geneva 4, Switzerland, b Division of Substance Abuse,
Department of Psychiatry, University Hospitals of Geneva, CH-1211 Geneva 14

Correspondence to: Dr Perneger perneger@cmu.unige.ch

KEY MESSAGES

A heroin maintenance programme may be a useful treatment option for
patients who do not succeed in conventional drug treatment programmes

Patients randomly allocated to the Geneva heroin maintenance programme
fared better that patients in conventional drug treatments in terms of
street drug use, mental health, social functioning, and illegal activities

Results of the trial apply only to a subgroup of severely addicted people
who failed repeatedly in conventional drug treatments

This evaluation does not distinguish between the effects of heroin itself
and the effects of other medical and psychosocial services that were
provided as part of the programme

There was less demand for the heroin maintenance programme than anticipated
and most control subjects declined entry into the programme at the end of
the study

ABSTRACT

Objective: To evaluate an experimental heroin maintenance programme.

Design: Randomised trial.

Setting: Outpatient clinic in Geneva, Switzerland.

Subjects: Heroin addicts recruited from the community who were socially
marginalised and in poor health and had failed in at least two previous
drug treatments.

Intervention: Patients in the experimental programme (n27) received
intravenous heroin and other health and psychosocial services. Control
patients (n24) received any other conventional drug treatment (usually
methadone maintenance).

Main outcome measures: Self reported drug use, health status (SF-36), and
social functioning. Results: 25 experimental patients completed 6 months in
the programme, receiving a median of 480 mg of heroin daily. One
experimental subject and 10 control subjects still used street heroin daily
at follow up (difference 44%; 95% confidence interval 16% to 71%). Health
status scores that improved significantly more in experimental subjects
were mental health (0.58 SD; 0.07 to 1.10), role limitations due to
emotional problems (0.95 SD; 0.11 to 1.79), and social functioning (0.65
SD; 0.03 to 1.26). Experimental subjects also significantly reduced their
illegal income and drug expenses and committed fewer drug and property
related offences. There were no benefits in terms of work, housing
situation, somatic health status, and use of other drugs. Unexpectedly,
only nine (38%) control subjects entered the heroin maintenance programme
at follow up.

Conclusions: A heroin maintenance programme is a feasible and clinically
effective treatment for heroin users who fail in conventional drug
treatment programmes. Even in this population, however, another attempt at
methadone maintenance may be successful and help the patient to stop using
injectable opioids.

INTRODUCTION

Many harmful consequences of heroin use stem from the illegal status of
street drugs.1-3 Drug substitution programmes may alleviate these
consequences,4 but not all addicts benefit: many continue using street
drugs, others drop out, others never enrol. Addicts may fail in oral
substitution programmes because they need the "high" caused by heroin
injection or the ritual of preparing and injecting the drug. Programmes
which provide intravenous heroin may reach such addicts.5-12

In Switzerland several programmes involving provision of intravenous
opiates were started in 1992-5. 13 14 Most were evaluated in a before and
after design. Only the Geneva heroin maintenance programme was conceived as
a randomised trial: eligible addicts were randomised either to immediate
admission or to a 6 month waiting list during which time they could receive
any other available drug treatment. The research question was whether the
experimental programme would improve participants' illegal drug use,
health, and social functioning.

METHODS

Study design and sample

This randomised trial compared outcomes at 6 months in patients allocated
to immediate versus delayed admission to the heroin maintenance programme.
The planned sample size was two groups of 40 patients. Programme and study
procedures were approved by ethics committees in Geneva and Berne.

Eligibility criteria were residence in the canton of Geneva since June
1994, age 20 years, addiction to intravenous heroin for 2 years, daily
consumption of opiates, social distress or poor health or both, due to drug
use, two or more previous unsuccessful attempts at drug treatment,
participation in evaluation, and giving up driving on starting heroin
maintenance.

Information about the programme was disseminated through drug abuse
treatment centres. Interested people were screened on the telephone by a
psychiatrist (FG), and those who seemed eligible were invited to an initial
visit. During this visit the psychiatrist confirmed the patient's
eligibility, explained programme procedures, obtained informed consent,
performed the baseline assessment, and allocated the patient to either
immediate or delayed admission by using computer generated random numbers
placed in sealed envelopes.

Experimental Programme

The programme clinic was established in September 1995 by the division of
substance abuse, Geneva University Hospitals, in central Geneva. Staff
included a psychiatrist, an internist, a social worker, five nurses, and a
secretary.

Patients attended usually three times daily. The dose of heroin was
established by the psychiatrist on the basis of patients' needs. Patients
were instructed in safe intravenous injection practices and could inject
the drug themselves. After the injection patients were observed for about
30 minutes. If a patient was intoxicated on arrival the usual dose was
halved. Oral opiates (methadone or morphine sulphate) were introduced
whenever patients wanted only one or two injections a day or if they had to
travel. Patients addicted to benzodiazepines received clorazepate
substitution treatment; all patients received psychological counselling,
HIV prevention counselling, social and legal support services, and somatic
primary care.

Control Treatment

Subjects in the control group were encouraged to select any drug treatment
programme available in Geneva, were enrolled immediately whenever possible,
and were given priority for admission to heroin maintenance after 6 months.

Outcome Variables

Outcome variables were consumption of street heroin and other drugs,
frequency of overdoses, risk behaviours for HIV infection, numbers of days
ill in past month, use of health services, health status, work status,
living arrangements, quality of social relationships, monthly living and
drug related expenditures, sources of income, and criminal behaviour. The
questionnaire (unpublished, based on addiction severity index) was
developed by the federal evaluation team, to which we added items to
explore specifically the past 6 months, including risk behaviours for HIV
infection, and the SF-36 health survey.15

ANALYSIS

The trial was analysed on an intention to treat basis. For continuous
outcome variables we assessed changes over time by the Wilcoxon matched
pairs test and differences between groups in change scores by the
Mann-Whitney U test.16 For dichotomous variables we used the McNemar's test
for before and after comparisons16 and tested the homogeneity of McNemar's
odds ratio to compare groups.17 When all changes were in the same direction
we compared proportions of individual subjects who changed status. Only
exact tests and confidence intervals were used.

RESULTS

Enrolment And Follow Up

Only 73 heroin users (52 men and 21 women, mean age 32 years) applied
between September 1995 and March 1996, and 57 were eligible. Among those
who were not eligible, 12 did not inject heroin regularly, three were not
Geneva residents, three refused to comply with evaluation, and one refused
to give up driving. Six eligible people delayed their decision and never
provided informed consent. Of 51 patients who agreed to participate, 27
were randomised to immediate and 24 to delayed admission. All experimental
group patients and 22 in the control group were reassessed 196 days on
average after enrolment (range 168-248); one person from the control group
filled only the SF-36 questionnaire. The two remaining patients in the
control group were alive at follow up but refused to cooperate.

Baseline Description

Participants (table 1) were typically young men who had been injecting
heroin for an average of 12 years, had attempted eight drug treatments
(range 2 to 21), and had experienced four drug overdoses (range 0 to 30).
They had a high prevalence of mental disorders and health status scores 1-2
SD below population norms.15

Table 1. Baseline characteristics of patients randomly enrolled into heroin
maintenance programme or assigned to 6 month waiting list, Geneva, 1995-6.
Values are means (SD) unless stated otherwise

Treatments Received

One patient allocated to the experimental group never showed up, and
another requested transfer to methadone maintenance after one day on
heroin. The 25 others received intravenous heroin on average on 168 out of
the first 183 days (oral opiates only were given on the remaining days); 20
patients received heroin on more than 80% of treatment days. There were no
medical problems with drug injections. The mean daily dose of intravenous
heroin was 509 mg (quartiles: 400, 480, 630 mg/day) in one to three
injections. Median dose remained stable during the trial (month 1 to 6:
460, 500, 470, 490, 500, and 480 mg/day). Several patients said that they
experienced symptoms of craving before injections but did not mind as they
knew that the next dose of heroin would be delivered on time.

In addition to heroin, all patients occasionally received oral opiates, on
78 days (43%) of 183 (range 8 to 150) days. Furthermore, 16 (59%) subjects
received clorazepate substitution therapy (median dose 60 mg/day).

During the 6 month follow up 19 of 21 people in the control group entered a
methadone maintenance programme, six a detoxification programme, and one a
residential programme. Duration of stay in each programme was not assessed.

Use Of Non-Prescribed Drugs

At follow up only one (4%) subject in the experimental groupthe person who
was never treated but still completed the follow up questionnairebut 10
(48%) in the control group still used street heroin daily (difference 44%;
exact 95% confidence interval 16% to 71%; table 2). All experimental
patients stopped daily use of street bezodiazepines, and their frequency of
overdoses decreased significantly.

Table 2. Impact of heroin maintenance programme on drug use, Geneva,
1995-6.Values are numbers (percentages) of subjects unless stated otherwise

Health Status

No changes were seen for physical problems or admission to hospital in both
groups (table 3). Among patients in the experimental group treatments for
mental problems increased and days with mental health problems decreased.
Self reported severe depression declined in both groups, but severe anxiety
decreased only in the experimental group. Changes in difficulty in
controlling violent behaviour and in the number of suicide attempts
favoured the experimental group.

Table 3. Impact of heroin prescription programme on health problems, use
of services, and HIV related behaviours, Geneva, 1995-6. Values are numbers
(percentages) of subjects unless stated otherwise

Use of condoms remained stable in both groups. Patients in the experimental
group no longer shared injection materials (only the non-attender (above)
continued this practice) and improved disinfection practices.

Health status scores improved more among experimental patients than among
controls (table 4). Differences between groups in before and after changes,
in SD units, were 0.54 (95% confidence interval 0.15 to 1.23) for physical
functioning, 0.45 (0.40 to 1.29) for role-physical, 0.18 (0.63 to 0.98) for
bodily pain, 0.14 (0.08 to 0.37) for general health, 0.22 (0.17 to 0.62)
for vitality, 0.65 (0.03 to 1.26) for social functioning, 0.95 (0.11 to
1.79) for role-emotional, and 0.58 (0.07 to 1.10) for mental health.

Social Functioning

Housing situation improved in both groups (table 5). Both groups remained
stable in their marital situation and occupational status and both
developed more social ties outside the drug scene. Both reported slightly
better relationships with their family and social circle (not shown).

Table 4. Impact of a heroin maintenance programme on heath related quality
of life, measured by means of the SF-36 health survey, Geneva, 1995-6

Table 5. Impact of heroin maintenance programme on social integration and
illegal activities, Geneva, 1995-6. Values are numbers (percentages) unless
stated otherwise

Dependency on "street life" decreased sharply in the experimental group,
less so in the control group. Charges for offences related to drug and
property decreased in experimental patients and increased in the control
group.

Legal income (work, loans, social benefits) remained stable in both groups
(table 6). Income from illegal activities (dealing drugs, commercial sex,
theft) decreased significantly in experimental patients. In particular,
monthly income from dealing drugs went from £1163 to none in the
experimental group and from £1143 to £1774 among controls (P0.03 for
difference between groups). Living expenses changed little in either group,
but patients in the experimental group reduced their drug expenses about
10-fold whereas those in the control group continued spending similar amounts.

Table 6. Impact of heroin maintenance programme on participants' financial
situation in previous month, Geneva, 1995-6. Values are mean (SD) Swiss
francs (1 Swiss franc£0.45)

Enrolment Of Controls At Follow Up

Unexpectedly, only nine (38%) of 24 controls enrolled in the heroin
maintenance programme at follow up. Of those who declined, most were
successfully treated in methadone maintenance programmes. Main reasons for
not wanting to start heroin maintenance were a satisfactory personal
situation and the desire to stop injecting drugs.

DISCUSSION

This study suggests that a heroin maintenance programme may be a feasible
and effective treatment option for severely addicted opiate users.
Acceptability was good, as 25 of 27 patients completed 6 months in the
programme on stable doses of intravenous heroin. The existence of the
programme in an urban neighbourhood caused no disturbance. Thus concerns
about feasibility18 need not hamper further evaluation of heroin
maintenance programmes.

The experimental programme was better than other available treatments in
several respects. Patients on heroin maintenance no longer used street
heroin or street benzodiazepines daily, their mental health and social
functioning improved, and they committed fewer suicide attempts, derived
less income from illegal activities (particularly from dealing drugs),
spent less money on drugs, and committed fewer offences, particularly drug
and property related offences. These results are not only significant but
also important for the participants' health and social functioning.

Our results are more favourable than those of the only previous trial of
heroin maintenance.7 The two studies, however, differ considerably.
Hartnoll's patients were less severely addicted, received fewer supportive
services, could take heroin home, and received only 60 mg of heroin daily.
Evaluation methods also differed: the British researchers relied on
participant observation while we used quantitative tools.

In other outcomes, experimental patients improved over time, but the
difference with patients in the control group was not significant. Examples
include fewer drug overdoses, better housing, better overall health status,
less severe anxiety, and better precautions against HIV. A larger trial
might determine whether heroin maintenance is superior to conventional
treatments in these respects. Improvements experienced by controls suggest
that even addicts who failed repeatedly in the past may benefit from
another trial of conventional drug treatment.

Finally, the experimental programme conferred no advantage in terms of
work, legal income, commercial sex, and use of street drugs other than
heroin and benzodiazepines.

LIMITATIONS OF STUDY

Our study has several limitations. Firstly, this was a small trial, similar
to initial evaluations of methadone maintenance,19-21 which threatens the
reliability of our findings. Secondly, all outcome measures were self
reported, which raises the issue of information bias. Thirdly, because this
study assessed global programme effects it cannot differentiate between
specific effects of heroin administration and those of other medical and
social services, such as mental health care and benzodiazepine
substitution. Our results do not support distribution of heroin without
such services and certainly not legalisation of heroin.3 We cannot exclude
that the benefits of our heroin maintenance programme were entirely
attributable to these additional services. Testing the specific
contribution of heroin injections would require a trial in which all
services but the prescribed opiate would be identical. Nevertheless,
psychosocial services alone would probably achieve little as such
programmes do not retain patients in treatment.22

We imposed no specified drug treatment to subjects in the control group
because only patients who failed repeatedly in conventional treatments were
eligible. We expected that needs and preferences would vary and wanted to
allow several different treatment attempts. This choice was consistent with
our research question (can heroin maintenance improve on existing
treatments?), but it restricts the generalisability of our results as
"existing treatments" differ by location.

Subjects who had never undergone treatment were excluded from Swiss heroin
trials to avoid enrolling patients who could benefit from conventional
treatments. Restriction of eligibility to addicts who had a tendency to
fail in conventional treatments, however, may bias against the control
group. Thus our results do not support heroin maintenance as a first line
treatment of heroin addiction. Eligibility criteria also prevented us from
assessing whether a heroin maintenance programme would attract addicts who
had not considered drug treatment previously.

Finally, interest in the heroin maintenance programme and enrolment in the
trial were less than anticipated. Whether this was due to insufficient
publicity, constraints imposed by the randomised evaluation, or lack of
need requires clarification. Furthermore, only nine of 24 in the control
group, all of whom had requested heroin maintenance at baseline, enrolled
into the programme after 6 months. Thus self perceived need for heroin
maintenance may change over time, particularly when conventional drug
treatment programmes are available.

Our study did not answer all relevant questions about heroin maintenance.
Further research should aim to replicate our findings in larger samples and
in other populations, include outcome variables that are not self reported,
explore the specific contribution of medical and psychosocial services to
overall programme benefits, assess the value of alternative routes of
heroin administration, and examine possible interactions between baseline
characteristics of patients and relative benefit of heroin treatment.

ACKNOWLEDGMENTS

Contributors: TVP (coguarantor) had ultimate responsibility for the
evaluation of the programme; he proposed and finalised the evaluation
design, assisted with data collection procedures and data quality control,
analysed the data, and wrote the paper. FG managed the experimental
programme; he assisted with study design, conducted or supervised data
collection, checked quality of data, discussed implications of results, and
revised the paper. MdR wrote the detailed study protocol, negotiated
acceptability of randomised study with authorities, discussed implications
of results, and revised the paper. AM (coguarantor) had ultimate
responsibility for the experimental programme; she helped with and approved
the study protocol, negotiated acceptability of randomised study with
authorities, discussed implications of results, and contributed to the paper.

Funding: Federal Office of Public Health (Berne, Switzerland), Swiss
National Science Foundation (Berne, Switzerland, career development grant
3233-32609.91 to TVP).

Conflict of interest: None.

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Copyright © 1998 by the British Medical Journal.

Checked-by: Richard Lake