MEDICALLY CONTROLLED PRESCRIPTION OF NARCOTICS .
A SWISS NATIONAL PROJECT

The research protocol and preliminary results are presented.

This is a version of a paper presented at the Vlth Intemational Conference on the Reduction of Drug Related Harm in Florence, March 1995.

INTRODUCTION

The project described in this article arose as a result of the addiction proneness which is comparatively high in the Swiss population for various classes or substances including alcohol and illegal drugs; a long standing tradition of medical and social treatment and support for substance abusers; and a comparatively well equipped and diversified system of care which characterises our treatment system.

For heroin-dependent people, various estimation methods result in a figure of approximately 30 000, in an overall population of 6.8 million, the primary response was the implementation of outpatient and residential drug free care. By 1994 there were 204 residential treatment centres. Methadone prescription, originally accessible without formal restrictions, became regulated by law in 1915. Maintenance is now practised extensively, as a rule accompanied by comprehensive medical and social care (Table 1). By the end of 1993 there were around 12 000 patients.

A large number of heroin addicts, still not in therapeutic contact or failing and dropping out from treatment, called for new initiatives. The comparatively high prevalence of AIDS cases in Switzerland contributed to the urge for new initiatives to reduce risk taking behaviour in injecting drug users. In public opinion polls, the drug problems rated repeatedly among the priorities of concern.

TABLE 1: Treatment for drug-dependent persons in Switzerland
• Long-standing tradition of non-profit organisations to care for alcoholics and substance users
• Abstinence oriented treatment for heroin and polydrug users (detoxification, TC type of long-term residential treatment, drug-free out-patient services) (1994: 204 residential institutions)
• Regimentation of methadone maintenance in revised narcotic law (prescribing doctors need authorisation by Cantonal Health Authority) in 1975
• National reports and recommendations on methadone maintenance (1983, 1989, 1995)
• Auxiliary services, low threshold, for drug users (contact centres, sheltered living, syringe exchange schemes, injection rooms, emergency services); implementation increased and decentralised since the late 1980s
• Treatment on court order increasingly accepted (residential and outpatient)
• Involuntary assessment and detoxification in psychiatric hospitals as a standard procedure if individually indicated
• Medically controlled prescription of narcotics (national scientific experiment since December 1993, expiring December 1996)

SETTING UP THE PROJECT

In 1990, the Federal Commission on Drug Related Problems (a subcommission of the Federal Commission on Narcotics) started a debate on diversified prescription of narcotic substances, based on the British experience and the Amsterdam morphine prescription project. Dr A. Mino was commissioned to prepare a report on previous experiments with prescribing heroin and morphine (Mino, 1990). Position papers by the Federal Office of Justice prepare the legal grounds for an eventual experimentation as a scientific experiment (according to Swiss narcotic law, heroin can be presribed for scientific reason only).

In February 1991, the Federal Government presented an action plan for new preventive and therapeutic initiatives, including medical prescription of narcotic substances as a scientific experiment (Bundesratsbeschluss, 1991). Guidelines were commissioned. The Commission on Narcotics and its subcommission approved a research plan which then was submitted to the Federal Government. A decree was issued (Verordnung des Bundesrates, 1992) and first trials started in January 1994, based on comprehensive scientific and practical preparations.

The project is a scientific experiment testing the feasibility, effectivity and cost effectiveness of diversified prescription schemes. At the same time, it is a therapeutic experiment testing the acceptability, retention rates and therapeutic results for heroin- dependent people who cannot profit sufficiently s from other forms of treatment. In addition, the project aims at attracting an increased proportion of heroin-dependent people into treatment (versus out of treatment). This objective is based on research evidence demonstrating that any kind of treatment has a potential to reduce risk-taking behaviour regarding an HIV infection or its passing on to others (Uchtenhagen et al.,1993).

The overall goal led to a definition of the therapeutic programme and the scientific programme with the elements shown in Table 2.

As in other evaluation studies concerning psychiatric treatment, this experimentation has to consider many aspects of potential benefits, side effects, usefulness and acceptability. In addition, feasibility and cost effectiveness have to be considered. An overview of the area to be covered by the research protocol is given below.

Various designs are needed in order to gain the necessary information. These were mainly double blind, randomised and individual attribution of substances to participants, plus specific designs for additional clinical, pharmacological and toxicological studies. Double-blind trials are designed in order to identify differential effects of heroin and morphine when administered intravenously (heroin is rapidly metabolised to morphine). It is important to know if differing patients' experiences with heroin and morphine correspond with differences which can be empirically demonstrated, or if it is mainly the result of differences in subjective expectations. On the other hand, randomised and individual attribution of substances are needed in order to determine effects and acceptability under experimental conditions as well asunder conditions that are similar to those used in daily practice.

TABLE 2: Programme
Therapeutic programme:
• on site controlled injections (no take home of injectable substances)
• comprehensive medical, psychiatric and social assessment
• comprehensive care, including sheltered living if needed
Scientific programme:
• data collection from therapeutic programme
• data collection from independent interviewers
•  data collection from third parties
• ànalysis of indivldual data measuring change
• analysis of aggregated data (pool)
• analysis per programme
• analysis per research design

TABLE 3: Research questions
Patient-related items:
• medical psychiatric consequences
• changes in addictive behaviour
• changes in coping behaviour
Substance-related items:
• pharmacological effects
• toxicological effects
• therapeutic applicability
Service-related items:
• feasibility of project
• effectivity of project
• cost-effectiveness of project
Global evaluation:
•  advantages/disadvantages in comparison to substitution with oral methadone
• recommendations for therapeutic practice and legislation

A special programme was designed for heroin dependent women, especially women engaged in risky activities such as prostitution. The effects of specific care provided in this subproject will be compared with those in women participants in other subprojects.

The main comparison group is formed by heroin dependent people entering selected programmes for methadone maintenance. The same research protocol applies for those persons as well as for participants in the project (Table 4).

The research plan has set a number of conditions which were accepted by the Federal Government. These conditions include the range of substances to be prescribed, the duration of the project and the size of the project, entry and exclusion criteria as well as the evaluation of the project (Table 5 ).

Not all subprojects started at the same time. Implementation was realised during a period of approximately 10 months. It is therefore not possible yet to give any systematic evaluation of data on outcome of treatment. On the other hand, there are already data on the feasibility, safety and acceptability of subprojects and of substances involved. Continuous evaluation of data on the characteristics of participants (442 by May 18 1995) shows to what extent the entry criteria are respected and the target population is in fact met (Table 6).

First results can also be given with respect to participants' compliance in the therapeutic and scientific programmes. The required medical and social data at entry are available for 93% respectively 94% of participants, independent extensive interviews for 83% (first independent interview is made within 4 weeks of entry into the project which results in a respective time lag). The drop-out rate is also, by mid-May 1995, 2 1%, lower than in most methadone maintenance programmes and much lower in comparison to residential treatment.

The data on the substances involved reveal important differences in side effects and acceptability. Whereas the therapeutic applicability of intravenous heroin is quite satisfactory, intravenous morphine has caused more frequent and more severe side effects (histamine-like reactions) than expected. In the randomised trials a higher drop-out rate in those who received morphine was the result. In the first double-blind trial, most participants identified correctly the substance received, and also identified date and substance of a switch from morphine to heroin (individual dates of switch were not known to staff and participants). The double-blind trial will be replicated in another subproject. It may be tentatively concluded that intravenous morphine is not suitable for routine maintenance, although preferred by some individuals. An additional clinical study, an extensive literature analysis and a special study on the side effects as evidenced in the project will be published in a special report. Experience with intravenous methadone, on the other hand. is not conclusive yet.

Based on these first results, the original research plan has been changed in one detail, namely the number of treatment slots with heroin prescription is increased and the number of treatment slots for morphine prescription reduced. The research protocol is unchanged (Figure 7).

CONCLUSION

Background, objectives and research plan of the project are described. The first results concern the feasibility, safety and acceptability of the project, as well Ss the characteristics of participants and their com pliance with the programme. Major side effects of intravenous morphine resulted in a reduction of morphine prescription. A first evaluation of therapeutic effects has been available since early 1996 (Uchtenhagen et al., 1995).

Professor Ambrose Uchtenhagen, Institut fur Suchtforschung, University of Zurich, Konradstrasse 32, 8005 Zurich, Switzerland.

REFERENCES

Bundesratsbeschluss vom 20 Februar 1991 zur Verminderung der Drogenprobleme.

Dobler-Mikola A, Uchtenhagen A, Gutzwiller F, Blattler R ( 1994). Social characteristics of participants in Swiss multicenter opiate trials at time of entry: Preliminary results. Psychiatrische Universitatsklinik Z&rich: Sektor West und Sozialpsychiatrie, Institut f&r Sozial- und Praventivmedizin derUniversitatZurich (Hrsg)

Mino A ( 1990). Analyse scientifique de la littérature sur la remise contrôlée d'héroïne ou de morphineX Expertise rédigée à la demande de l'Office Fédéral de la Santé Publique, Berne.

Uchtenhagen A ( 1994). Diversifizierte Verschreibung von Betaubungsmitteln an Heroinabhangige: Grundlagen, Versuchsplan, Begleitforschung. Schweiz. Rundschau Med. PRAXIS 34: 931-6

Uchtenhagen A, Zimmer Höfler D, Dobler-Mikola A ( 1993 ) . Psychosoziale Aspekte der HlV-lnfektion bei Heroinabhangigen. Studie im Rahmen des Nationalen Forschungsprogramms Nr. 26. Schlussbericht zuhanden des Schweizerischen Nationalfonds.

Uchtenhagen A, Gutzwiller F, Dobler-Mikola A, Blattler R ( 1995 ) . Versuche fur eine drztlFche Verschregbung son Betaubungsmztteln: Zwgschenbencht der Forschungsbeauftragten. Institutf&rSuchtforschung, Zurich.

Verordnung des Bundesrates uber die Förderung der wissenschaftlichen Begleitforschung zur Drogenpravention und Verbesserung der Lebensbedingungen Drogenabhangiger. Bern, 1992