Opioid use is the number one reason for seeking substance misuse treatment across 30 European countries. Opioids are drugs derived from the opium poppy and these include the drug heroin (EMCDDA, 2015).

Heroin dependence has negative consequences for both the individual and society as persistent use of the drug is associated with poor health, criminal offences and damaged personal relationships (Ferri et al, 2011). Drug-free treatments and substitution treatments are the two interventions used to overcome heroin dependence.

Methadone is the most common substitution treatment in the EU, however, heroin prescribing is well established in Denmark, Germany and The Netherlands, an option in the UK and Spain, and currently under investigation in Belgium and Luxembourg (EMCDDA, 2015).

A recent systematic review and meta-analysis aims to compare supervised injectable heroin (SIH) as a treatment for heroin users who have not responded to more standard treatments such as methadone maintenance treatment (MMT) or residential rehabilitation (Strang et al, 2015).

Methods

Electronic databases (PubMed, Web of Science and Scopus) were searched for studies that reported on the effects of SIH treatment in participants with heroin-dependence unresponsive to standard treatments.

The studies had to have opiate use, retention in treatment, mortality and side-effects as outcome variables.

Studies were excluded if they were methodological papers, assessed unsupervised heroin treatment provision, focused on policy aspects, cost effectiveness, community perspectives or patient satisfaction.

The meta-analysis focussed on Mantel-Haenszel random effects pooled risk ratios for SIH treatment compared to the comparison groups.

Results

There were a total of six papers included in the main review and meta-analysis. These studies were based in Switzerland, The Netherlands, Spain, Germany, Canada and England.

All studies explored SIH compared to MMT (oral methadone) in chronic heroin-dependent individuals who have repeatedly failed in orthodox treatment.

The results of rate of retention and the use of illicit heroin following treatment are shown in Table 1. The rates of retention varied across studies, with only one study reporting a lower rate of retention for the SIH group (Van den Brink et al, 2003). The statistical evidence indicated a lower rate of illicit heroin use in individuals receiving SIH treatment in all six studies.

Table 1: Retention in treatment and use of illicit heroin results

Study	Retention in treatment	Use of illicit heroin
Perneger et al, 1998	SIH 93% vs MMT 92%	p = 0.002
Van den Brink et al, 2003	SIH 72% vs MMT 85%	P = 0.002
March et al, 2006	SIH 74% vs MMT 68%	P = 0.02
Haasen et al, 2007	SIH 67% vs MMT 40%	P < 0.001
Oviedo-Joekes et al, 2009	SIH 88% vs MMT 54%	P = 0.004
Strang et al, 2010	SIH 88% vs MMT 69%	P < 0.0001

Meta-analysis

A meta-analysis was conducted to explore retention in treatment, mortality outcome and side-effects.

• Retention in treatment was significantly better for the SIH than for the MMT treatment groups as demonstrated by four studies; RR = 1.37, 95% CI = 1.03 to 1.83
• Mortality was lower in the SIH than in the MMT treatment groups but this was not significant; RR=0.65, 95% CI = 0.25 to 1.69
• There was a higher risk of side effects in the SIH compared to the MMT treatment groups based on analysis of five studies; RR = 4.99, 95% CI = 1.66 to 14.99

Strengths and limitations

All of the included studies were randomised controlled trials comparing traditional oral MMT to SIH in participants with chronic heroin-dependence who have not been successfully treated. The review followed PRISMA guidelines and was inclusive of all languages and publication dates, so the likelihood of important papers being excluded is minimal.

In this review the authors focussed on supervised administration of heroin only, which contrasts with a 2011 Cochrane Review that also included studies where heroin was prescribed for take-home administration (Ferri et al, 2011). By restricting the inclusion criteria, stronger conclusions can be made about the efficacy of this type of treatment which may guide the introduction of new interventions. Additionally the authors’ address several key misgivings about SIH, which further supports the argument that SIH is an effective treatment for treatment-resistant heroin dependence. For example, the concern that SIH may undermine other existing treatments is countered by the difficulty in recruitment experienced by many of the six trials under review.

There are some limitations, e.g. the safety of injectable diamorphine requires further research as the instances of sudden-onset respiratory depression is at a rate of about 1 in 6,000 injections.

Conclusions

The authors concluded that:

Based on the evidence that has been accumulated through these clinical trials, heroin-prescribing, as a part of highly regulated regimen, is a feasible and effective treatment for a particularly difficult-to-treat group of heroin dependent patients.

The importance of supervision during administration is emphasised throughout the review. As mentioned above, all of the participants engaged in SIH had previously repeatedly failed in orthodox treatment, however, the evidence supports SIH as a treatment option for these individuals.

Links

Primary paper

Strang J, Groshkova T, Uchtenhagen A. et al. (2015) Heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addiction. Br. J. Psychiatry 2015;207:5-14. doi:10.1192/bjp.bp.114.149195.

Other references

EMCDDA (2015) European Monitoring Centre for Drugs and Drug Addiction. emcdda.europa.eu. 2015. Available at: http://www.emcdda.europa.eu

Ferri M, Davoli M, Perucci CA. Heroin Maintenance for chronic heroin-dependent Individuals. Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No .: CD003410. DOI: 10.1002 / 14651858.CD003410.pub4.

Van den Brink W, Hendriks VM, Blanken P, Koeter MWJ, van Zwieten BJ, van Ree JM. (2003) Medical prescription of heroin to treatment resistant heroin addicts: two randomised controlled trials. BMJ 2003;327(August):310. doi:10.1136/bmj.327.7410.310.

Perneger T V, Giner F, del Rio M, Mino A. (1998) Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments. BMJ 1998;317(July):13-18. doi:10.1136/bmj.317.7150.13.

March JC, Oviedo-Joekes E, Perea-Milla E, Carrasco F. (2006) Controlled trial of prescribed heroin in the treatment of opioid addiction. J. Subst. Abuse Treat. 2006;31:203-211. doi:10.1016/j.jsat.2006.04.007. [PubMed abstract]

Haasen C, Verthein U, Degkwitz P, Berger J, Krausz M, Naber D. (2007) Heroin-assisted treatment for opioid dependence: Randomised controlled  trial. Br. J. Psychiatry 2007;191:55-62. doi:10.1192/bjp.bp.106.026112.

Oviedo-Joekes E, Brissette S, Marsh DC, et al. (2009) Diacetylmorphine versus methadone for the treatment of opioid addiction. N. Engl. J. Med. 2009;361:777-786. doi:10.1056/NEJMoa0810635. [Abstract]

Strang J, Metrebian N, Lintzeris N, et al. (2010) Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. Lancet 2010;375(9729):1885-1895. doi:10.1016/S0140-6736(10)60349-2. [Abstract] [Watch Prof John Strang talk about the RIOTT trial]