Status Report On The Medical Prescription Of Narcotics

Summary

According to several decisions of the Swiss Federal Government a longitudinal study embedded in a multicentric research design has been set up in order to analyse the long term effects of the medical prescription of different narcotics (i.v. heroin, i.v. morphine and i.v. methadone) in 700 long term drug addicts with signs of severe social disintegration. The following dependent variables are considered: health status, risk behaviour, multi drug use, psychological well being, social disintegration, delinquent behaviour and work capacity. The trials are taking place in eight Swiss cities. The rationales of the prescription trials are presented together with a brief description of the trials, supplemented by first observations. From January 2nd 1994 to January 1st 1995 a total of 422 patients has been admitted to the prescription programmes. 288 patients have been admitted to heroin, 71 patients to morphine and 63 patients to i.v. methadone programmes. Actually 232 patients are treated in heroin prescription programmes, 37 in morphine prescription programmes and 51 patients in i.v. methadone prescription programmes. An additional study with 16 patients took place in order to test the side effects of morphine prescription. The feasibility of the heroin prescriptions has been demonstrated in the course of 1994 with no major incidents. For the morphine condition, side effects were observed. Both i.v. morphine and i.v. methadone were less acceptable to drug addicts than heroin and for both substances there were lower recruitment rates. Since October 1994 an adaptation of the trials is planned according to a decision of the Federal Government.

Objectives of the multicentric research trials

The number of drug addicts in Switzerland who are consuming regularly i.v. substances is estimated to be about 25,000-30,000 (the population of Switzerland is about 7 Mio.). In spite of a wide spread network of institutions for therapy and substitution programmes with oral methadone (1993: 15,000 patients in treatment) a group of socially disintegrated and severely addicted patients could not be addressed by the existing treatment system. For this group of addicts all other treatment efforts had failed so far. The trials for the medical prescription of narcotics were supposed to approach this subgroup of addicts. For the overall research project the following objective is pursued:

The trials are set up in order to study the feasibility of the medical prescription of narcotics to severely dependent patients in a multicentric research study.

The following objectives are stated for each individual patient entering the trials:

• health risks in severely dependent persons should be reduced
• physical and psychic health should improve
• social integration should improve in particular with respect to work capacity
• distance to the drug scene should augment
• reduction of criminal behaviour should be observed

Several other objectives concern the investigation of pharmacological and physiological research questions with respect to pharmacokinetics, metabolic processes and substance specific questions (1).

In order to pursue questions related to the pharmacological effects of the different drugs as well as questions related to physical and psychic health, the original research design is based on the one hand on a multifactorial plan and on the other hand on the agglutination of longitudinal case studies.

The legal basis of the medical prescription of narcotics

The legal basis of the medical prescription of narcotics is constituted by the Swiss law on narcotics (1951) (2), by a decision of the Swiss government to take action against the widespread negative consequences of illegal drug use in Switzerland, dating from February 20, 1991 (3), and three further decisions taken after a long process of consensus building. On September 29, 1991 the Federal sub-commission on drug questions proposed to enlarge the medical prescription of narcotics including heroin. In November 1991 a proposal for a federal regulation, not including heroin, was sent to all cantonal governments and to major political and professional influence groups for comments and propositions. The evaluation of the stances taken by the cantonal governments and the different political and professional organisations showed a clear majority demanding to include heroin in the planned prescription of narcotics. Following the majority, the government decided on the general principle on May 13, 1992 to include heroin in the framework of a research design. A federal regulation was decided upon on October 21, 1992 and finally came into effect on November 15, 1992 (4). The regulation treats the necessity to scientifically evaluate actions taken by the government to reduce drug related problems and specifically states the general framework of the medical prescription of narcotics. On October 3rd, 1994 the Swiss government decided to modify the regulation of October 1992, in such a way that the number of heroin prescriptions shall be limited by the pertinent research questions that might be asked (5). Any modification of the research plan has to be decided upon by the Swiss Govemment.

Outline of the original research design

Patients and projects are assessed by means of a uniform evaluation protocol set up by a joint group of the Federal Offfice of Public Health and of scientific experts in different domains. The main responsibility for the research outline was in the hands of Prof. Ambros Uchtenhagen, Department of Psychiatry, University of Zurich (annex 2). The research outline is divided in five major trials:

1. A double blind study with a control study with randomized design only. This study was designed in order to evaluate the differential effects of heroin and morphine comparing objective and subjective substance effects.
2. Randomized prescription of heroin, morphine and methadone in one city.
3. Individualized prescription of heroin, morphine and methadone in various cities (context effects).
4. Individualized prescription of heroin, morphine and methadone in one city (control for trial 2 and 3).
5. Individualized prescription of heroin, morphine and methadone in a treatment project specifically designed to correspond to the needs of drug injecting women. The women in the other trials serve as controls.

In all the trials intravenously applied drugs are prescribed in combination with oral methadone in order to facilitate social reintegration, to avoid needle dependence, to encourage less risky drug consumption, to facilitate the pursuit of oral methadone substitution, once the trials are over and to minimize maintenance cost for the treatment facility. In addition to oral methadone less risky forms of opiate consumption are considered (smoking, oral applications).

Urine samples are analyzed once a month, complemented by regular checks, effectuated by recognized laboratories. In addition blood samples are analyzed by a specialized research institute every six months.

For comparison reasons a large sample of patients with oral methadone prescription is evaluated in parallel by means of an abreviated protocol. This study is not presented here in detail (6).

The overall research design- has been approved by the Ethical Committee of the Swiss Academy of Medical Sciences. An additional approval is required by local ethical committees for each project.

Authorizations for prescriptions

Authorization for prescription of heroin is given by the surgeon general of the respective canton and by the pharmaceutical division of the Federal Office of Public Health (FOPH), which is also in charge of the acquisition, control, preparation and distribution of the substances and of the necessary security measures.

For the other prescriptions an authorization of the surgeon general of the canton is needed, who by law is entitled to authorize the prescription of morphine, cocaine and methadone. The pharmaceutical division of the FOPH registers all prescriptions in the context of the trials.

Recruitment of patients

All patients wishing to participate in the trials are demanded to sign a statement of informed consent. Participation in the trials is on a voluntary basis. Patients have also to agree to participate in the research. Changement to other treatments (e.g. oral methadone substitution ) than those proposed can be demanded at any time.

Patients are admitted on the basis of a very comprehensive assessment procedure, including patients history, verifed past institutional experiences, and a comprehensive medical examination including voluntary serological testing.

Only those patients are considered for admission for whom a 2 years dependency of heroin with daily use and failure in at least two therapeutic efforts (withdrawal treatment, therapeutic communities, methadone programmes, etc.) can be demonstrated. The patients should be at least 20 years old and show deficits with respect to physical or psychic health and/or with respect to social integration according to the Addiction Severity Index (work, housing, relationships, delinquency, prostitution). There should be provided good reasons that a different therapeutic programme is of no utility to the patient.

Those patients which for health reasons or because of acute psychotic disorders are not able to fully participate in the programme are not admitted. Violence on the prescription site or the smuggling in or out of substances (such as cocaine) and other infractions of the house rules are reasons for exclusion.

Counseling

Patients taking part in the trials have to agree, in addition to the prescription modalities, to a treatment and counselling programme, which has a compulsory and an optional part.

It is well known from methadone studies that narcotics prescription is supposed to be more effective if it is administered in a counselling structure that enhances social integration. It is for these reasons that structural guarantees are demanded of each site taking part in the trials. These guarantees include weekly counselling for the patients, options for further treatments such as family therapy, and optional offers for day structure, work, and housing. These additional demands are quite costly and constitute important charges for the sites, for the local authorities, and for the cantons.

Development of the prescription programmes

Based on the regulation of the Federal government of October 21st 1992 the cantons and cities were invited to present detailed projects according to the above mentioned research plan. The deadline for the projects was May 15th 1993. In June 1993 the Swiss Federal Office of Public Health agreed to accept 9 projects in 8 cities (Basel, Berne, Fribourg, Olten, Schaffhausen, Thun, Zurich and Zug).

The first projects started in January 1994 in Zurich. In six out of eight cities prescription has already started. From January 2nd 1994 to January 1st 1995 a total of 422 patients has been admitted to the prescription programmes. 288 patients have been admitted to heroin, 71 patients to morphine and 63 patients to i.v. methadone programmes. Actually 232 patients are treated in heroin prescription programmes, 37 in morphine prescription programmes and 51 patients in i.v. methadone prescription programmes.

The double blind and random assignment study in Thun and Olten has already taken place. In Thun 10 patients were assigned to heroin and 15 patients to morphine, in Olten 7 patients were assigned to heroin and 7 patients to morphine. Because of side reactions and problems with recruitment and acceptance patients in the morphine groups in both centers had to be moved to the heroin groups (22).

In the heroin and morphine condition patients pass by the treatment center three times a day for injection and are supplemented with oral methadone in case of necessity. In the i.v. methadone condition patients pass by the treatment center once a day. In all conditions patients participate in weekly counselling sessions and are taken care of for their immediate needs with respect to work, housing and occupancy during the day. The treatment centers have the same characteristics as well structured oral methadone maintenance clinics.

Assessment of data

Patients case history and daily prescription practice is registered on site. Independent intervieviers collect additional data by interviewing the patients and the staff twice a year. All data are collected according to a standardised evaluation protocol. The following sets of variables are considered for evaluation: Somatic variables (general health status, subjective well being), risk behaviour with respect to health, HIV and Hepatitis, psychiatric variables (self ratings, psycho-pathological findings including drug induced psychoses), life style and social integration (work capacity, lodging, leisure time activities, management of daily life, social network, contacts with the drug scene, delinquency behaviour, social interaction, sexual risk taking behaviour), dependency behaviour (multi drug use, side consumption), pharmacology and toxicology (tolerance, side effects, withdrawal symptoms), therapeutic usefulness (retention, compliance, usefulness of various galenic forms, subjective substance effects), feasibility of the trials, effhciency, other variables with respect to the evaluation of the global programme.

All observations and changements of treatment are registered in computer based standardised data sheets. All personal data are rendered anonymous for evaluation purposes.

First preliminary findings

• general remarks
  
• heroin trials
  
• morphine trials
  
• trials with methadone
  
• side reactions

From the first 12 months of the research project in progress some preliminary observations can be stated, based on the registration data of the Federal Office of Public Health and on reports from the individual prescription sites (7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 22) as well as first data from the researchers (annex 1). They can be summarised as follows:

X. a. general remarks

During the observation period of 12 months the feasibility of the prescription trials has been demonstrated. Reports of the projects and the first research report show that the target groups have been largely met. During the treatment period no major incidents with respect to security occurred.

All trials reported less difficulties with respect to recruitment and acceptance for the heroin groups. In randomized trials, the better acceptance of heroin was clearly demonstrated. Side reactions were more often registered in morphine groups than in heroin groups.

In summary:

• the feasibility of the prescription trials has been demonstrated
• target groups have been largely met
• there were no major incidents with respect to security
• heroin was more acceptable to patients and was better tolerated than both morphine and i.v. methadone

X. b. heroin trials

In heroin groups patients were easily recruited and treatment was well accepted. Frequent minor histaminic reactions were also observed (17). Reports of the projects showed that compliance in the heroin trials was good (8, 9). Approximately 10% of the heroin patients dropped out or were banned from the site and another 10% of the patients moved to other treatment programmes (oral methadone, abstinence oriented). The retention rate in heroin groups up to now is close to 80%. Health status is stabilising and mostly improving and social integration is improving, too (8, 9).

In summary:

• patients for the trials were easily recruited
• the heroin prescription was well accepted
• heroin does lead to some side effects including histaminic reactions
• the compliance in the heroin trials was reportedly good
• approximately 10% of the heroin patients dropped out or were banned from the site
• approximately 10% of the patients moved to other treatment programmes (oral methadone, abstinence oriented)
• the retention rate is close to 80 %
• the health status is stabilising and mostly improving
• social integration is improving

X. c. morphine trials

In morphine trials difficulties with respect to acceptability, recruitment and retention rate were observed. In randomised trials assignment to the morphine condition was frequently the cause of dropping out. Histaminic reactions occurred frequently, dependent on modality of application and on dosage. Adequate injection techniques and prolonged treatment reduced histaminic reactions. The absolute numbers in the morphine condition are too small to be interpretable.

In summary:

• morphine presented difficulties with respect to acceptability, recruitment and
• retention (reflected in the low absolute numbers of patients recruited)
• strong histaminic reactions were observed in the morphine condition
• histaminic reactions were dependent on modality of application and on dosage
• histaminic reactions diminished in some patients after prolonged treatment.

X. d. trials with i.v. methadone

The recruitment of patients presented major difficulties (see low absolute numbers of patients). All concerned projects reported major problems in recruitment. Minor problems due to the large volume of injected substance were reported. The absolute numbers in the methadone condition are too small to be interpretable.

X. e. side reactions

Frequent histaminic reactions were observed in the first project that started with the prescription of morphine. Subsequently the prescription of morphine was stopped and on recommendation of an expert group a clinical study to evaluate the severity of these side reactions was started. Based on the results of this study (18) the expert group had no objections to continue studying the prescription of morphine in the projects and gave recommendations on dosage and application mode. In spite of these measures, histaminic reactions were still often observed and lead to recruitment difficulties and a decrease in acceptance. The expert group then recommended to modify the research plan, in order to take into account these observations (19 and annex 4).

In the heroin condition histaminic reactions were also observed, though the patients had to be questioned specifically on symptoms (17 and annex 4). The patients seemed to be accustomed to such reactions and judged those as quite normal.

In i.v. methadone groups several complaints and problems due to the large injection volumes were reported.

Conclusion

The medical prescription of narcotics in the framework of the Swiss trials constitutes a well planned multicentric research study. This study is supposed to shed light on some controversial questions (20, 21). First observations seem to indicate that the prescription of narcotics, especially of diamorphine could be an effective means to improve health and living conditions at least temporarily of severely addicted patients for whom other treatment efforts have failed so far. The experiences of the first 12 months of the prescription trials are encouraging.

The original research plan requires modifications. This is especially true with respect to the size of the different groups. However, as has been originally planned, the prescription of morphine, heroin and injectable methadone shall be maintained. Based on the present experience, an adaptation of the ratio of the group sizes of the three modalities of prescription shall be envisaged. Morphine and i.v. methadone prescriptions cannot be implemented as anticipated. However, the prescription of heroin can be envisaged to a larger extent, in order to maintain total cohort size. Swiss Federal Office of Public Health. "Status Report on the Medical Prescription of Narcotics." Switzerland: Swiss Federal Office of Public Health. January 1995

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