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This entry is our account of a review or synthesis of research findings selected by Drug and Alcohol Findings as
particularly relevant to improving outcomes from drug or alcohol interventions in the UK. Entries are drafted
after consulting related research, study authors and other experts and are © Drug and Alcohol Findings.
Permission is given to distribute this entry or incorporate passages in other documents as long as the source is
acknowledged including the web address http://findings.org.uk. However, the original review was not published
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text for explanatory notes. The abstract is intended to summarise the findings and views expressed in the
review. Below are some comments from Drug and Alcohol Findings.

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Heroin maintenance for chronic heroin-dependent individuals.


Ferri M., Davoli M., Perucci C.A.
Cochrane Database of Systematic Reviews: 2010, Issue 8.

For the first time an authoritative review has combined results from all the trials to date
of long-term heroin prescribing for the management of heroin addiction. Its analyses
reveal several significant or probably significant advantages for patients previously failed
by methadone.
Abstract Prescribing heroin for the treatment of heroin addiction is today generally seen
as a 'rescue' option for patients who have not benefited sufficiently from methadone
maintenance. This updated review and meta-analysis from the respected Cochrane
collaboration adds new studies of the treatment from England, Spain and Canada,
supplementing the earlier British, German, Swiss and pair of Dutch studies. The aim was
to integrate findings on injectable (or in one case, smokable) 'heroin maintenance' as
compared to more conventional oral methadone treatment, but also to any other
comparators available in the literature, without limiting the selection to trials which
allocated patients at random. In the event, seven of the eight relevant studies did
explicitly compare heroin maintenance to oral methadone; the remaining study also
effectively did so, since all but a few of the control group patients who had to find other
sources of help in fact enrolled in methadone programmes. The review assumed that all
patients were chronic heroin addicts since only these patients would qualify for such
treatments. Studies typically recruited local addicts who had regularly used illicit heroin
for several years and who had not done well in previous non-heroin based treatments.

Main findings
Over the periods of the eight studies, for every 100 patients retained in treatment on
methadone, another 23 were retained on heroin, almost a statistically significant
advantage (ie, unlikely to have happened by chance). In the Dutch studies heroin
patients faced stricter disciplinary discharge rules than methadone patients, biasing the
retention rates. Leaving these studies out, heroin's advantage rises to another 43

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patients and becomes statistically significant. Similar results are found if the analysis is
restricted to the more recent (and more tightly controlled) studies.
Across the five studies to report this, for every 100 patients prescribed methadone who
relapsed to use of illicit heroin, just 70 did so when prescribed heroin, very nearly a
statistically significant advantage. Three studies also documented use of other
substances; here there was a statistically significant advantage for prescribed heroin, the
ratio being 100 on methadone to just 63 on heroin.
Across the six studies which reported on patient deaths, there were so few that the
relative safety of heroin- and methadone-based treatments could not be assessed.
Slightly fewer (0.9 in every 100 patients versus 1.2) heroin patients died, but on the
other hand, significantly more adverse medical events short of death were recorded
among the same patients ± an extra 61%.
A 20% reduction in self-reported criminal activity among heroin compared to methadone
patients just failed to reach statistical significance. However, a significant extra reduction
in average days involved in crime per month recorded in the Spanish study could not be
incorporated in the calculations because this measure was incompatible with those of the
other studies. Just two studies reported on imprisonment, of which the German trial was
the only one to have tested modern-day treatments. In this study the numbers
imprisoned were significantly and substantially fewer (a near halving) on heroin
compared to methadone. Convictions too were fewer in the first 12 months of the study;
50% of heroin patients were convicted compared to 66% of methadone patients. In the
studies reporting these outcomes, employment rates and improvements in family
relationships did not significantly differ between heroin and non-heroin patients; possibly
the need to attend the clinic to take prescribed heroin two or three times a day
counteracted the expected gains.

The reviewers' conclusions


The available results demonstrate limited statistically significant positive effects of heroin
(plus flexible dosing with methadone) with regard to most of the outcomes considered.
Results are consistent across studies except (as explained above) for the Dutch studies
which recorded better retention in the control group. All the authors of the studies
highlighted the risks of adverse events. This risk warrants the provision of heroin only to
patients who have clearly been failed by methadone treatment and only in centres
equipped to respond to emergencies. What counts as 'failure' in this context remains to
be clearly delineated. Certain disadvantages including poverty, lack of family support,
and psychiatric problems are associated with poor compliance and response to many
kinds of medical treatments. Since everywhere resources are limited, the open question
is whether it is advisable to allocate patients to more expensive medications like heroin,
rather than trying to address more effectively the identified health and social predictors
of non-compliance and relapse which prevent methadone treatment working as well as it
might. Given the higher rate of serious adverse events, the risk-benefit balance of heroin
prescription should carefully be evaluated before the treatment is implemented in clinical
practice. Heroin prescription should remain a treatment of last resort for people failed by
conventional maintenance treatment. The capacity of addiction services and whether the
treatment can be afforded in the long term should carefully be assessed beforehand.

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The very cautious conclusion reached by the reviewers might easily have
been more positive with some justifiable adjustments to the pool of studies included in
the analyses or if the included outcomes had been only a fraction different. In particular,
the early British trial could justifiably have been considered a trial of such a different kind
of heroin-based treatment that it could have been analysed separately. Give such
adjustments, the advantage in retention became statistically significant and quite
substantial ± important because substitute prescribing treatments tend to be like an on-
off switch; while patients remain in treatment they quickly improve and most do
relatively well, but a rapid reversion to regular illicit heroin use with all its consequences
is common if they drop out or are forced out of treatment.
Similarly, omitting the early English trial might have led the nearly significant heroin
relapse comparison to have become statistically significant. Results for other substances
were significant without adjustment. The death toll could not have been expected to be
significantly different but still favoured heroin and would have done so more clearly had
the early English trial been separated out. The higher incidence of adverse effects
recorded among heroin patients may largely have been due to the fact their injecting ±
and any resultant immediate complications ± were observed by the clinics, while any
injecting by methadone patients would not have been. Had results from the Spanish trial
been able to be included in the analysis, then the near significant extra reduction in crime
among heroin patients may also have crossed the threshold to statistical significance.
For Britain the RIOTT trial conducted at clinics in London, Darlington, and Brighton
between 2005 and 2008 is the vital study. The questions posed by the study were
whether patients who remained wedded to street heroin despite extensive treatment
were simply beyond available treatments, whether it was just that their current oral
treatment programmes were sub-optimal, or whether they would only do well if
prescribed injectable medications. Each of these three propositions was true for some of
the patients. A third did seem beyond current treatments even as extended and
optimised by the study. For a fifth, 'all' it took was to individualise and optimise dosing
and perhaps also psychosocial support and treatment planning in a continuing oral
methadone programme. But despite pulling out many stops to make the most of oral
methadone, nearly half the patients only did well if prescribed injectable medications,
with heroin by far the better option than methadone at suppressing illegal heroin use.
The upshot was that the most reliable option in terms of securing a divorce from regular
illegal heroin injecting was to prescribe the same drug to be taken in the same way, but
legally and under medical supervision. As defined by the study, two-thirds of these
seemingly intractable patients responded well to this option. However, from a conference
presentation it seems injectable medications and heroin in particular had a far less clear-
cut advantage in respect of crime, health, and quality of life.
Conclusions similar to those reached by the featured review have been reflected in UK
national clinical guidelines and in guidance issued by England's National Treatment
Agency for Substance Misuse. In particular the latter is clear that injectable prescribing
should be considered only for the minority of patients with persistently poor outcomes
despite optimised oral programmes, and that the priority should be improving the
effectiveness of oral maintenance treatment for the majority.
Apart from the obvious and serious issue of cost, there is in any event a major logistical

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problem in extending heroin prescribing programmes based as recommended on


supervised consumption at the clinic. Studies in continental Europe and Britain have
shown that requiring on-site injecting or smoking of heroin several times a day is
feasible. However, this can only work for patients who can easily and quickly get to the
clinic. Unless the network of heroin prescribing centres is greatly expanded, on-site
consumption will leave large parts of Britain unserved, especially rural areas. The
inconvenience of on-site consumption can be tempered by allowing patients to skip visits
and take oral medication instead, an opportunity most took advantage of in Swiss trials.
Insisting instead on the return of used ampoules ± a tactic used with seeming success in
a study in London ± may be a less intrusive and less expensive way to prevent diversion.

For more on substitute prescribing for heroin addiction see this Findings hot topic. For
heroin prescribing studies in particular run this search on the Findings site, and especially
see this Findings review and a later review which paid careful attention to the context of
the studies and the details of the treatments.
This draft entry is currently subject to consultation and correction by the study authors and other experts.

Last revised 22 September 2010


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