BENZODIAZEPINES IN THE ILLICIT DRUGS SCENE

THE UK PICTURE AND SOME TREATMENT DILEMMAS*
*Based on the paper presented at the Second International Conference on the Reduction of Drug-related Harm, Barcelona, April 1991.

Sedatives have always been associated with chaotic polydrug use. Nicholas Seivewright and colleagues ask: 'Can we do harm reduction with benzodiazepine users?'


A great deal has been written on the subject of benzodiazepine dependence since it was demonstrated, around 10 years ago, that physical dependence could occur after use of ordinary therapeutic dosages of these drugs (Petursson and Lader, 198 1; Tyrer et al., 198 1 ). This contrasted with the previous belief that a lack of physical dependence was one of the great advantages which the benzodiazepines conferred over their predecessors the barbiturates, and the subject has been one of great medical and public concern. Recently, however, drug workers in many countries in the world have been seeing a form of benzodiazepine usage which is simply not in the text books, i.e. their use, often in extreme dosage, by illicit drug users in the context of polydrug use. There is little guidance to be had from the literature on either the nature or the management of such situations, as the overwhelming focus, even in literature aimed at those treating illicit drug users, has been on evidence derived from users solely of low dose prescribed amounts, and it is our experience that responses of treatment agencies to the use of benzodiazepines by illicit drug users vary extremely widely.

The purpose of this paper is therefore twofold: first, some evidence will be presented from a study we have undertaken in the UK which provides the most substantial data so far on the use of benzodiazepines by illicit drug users, and secondly, we will attempt to identify some of the dilemmas which treatment services face in the management of this problem that may be responsible for the lack of consensus on most aspects of the subject. In summarising, we will, however, try to make reference to appropriate clinical advice to follow in the treatment situation, as it is after all our aim that readers should be more informed rather than more confused by the end of our paper!

There have been some studies undertaken of the use of benzodiazepines by illicit drug users, but these have usually been small in scale and have investigated highly selected patient groups, such as patients in methadone maintenance clinics or individuals specifically referred for benzodiazepine abuse. It is not possible to review that literature here, but interested readers are referred to studies by Perera et al. (1987)andRoben and Morrison (1992) in the UK and by Busto et al. (1986) in Canada. Some very important evidence on this subject has recently been presented by Klee et al. (1990) who demonstrated, within a study of polydrug use, very strong associations between the use of the benzodiazepine drug temazepam and a wide range of high-HIV-risk, injecting and sexual behaviours. Exactly why temazepam and risky practices are associated in that way is not yet clear, although it is possible to speculate regarding the amnesia and confusion that appear to be induced by high-dose use of that drug, but this is a clear indication that the use ofbenzodiazepines mustbe carefully attended to in programmes of treatment of drug addiction that are based upon a harm-reduction approach.

A STUDY OF PREVALENCE AND PATTERNS OF BENZODIAZEPINE USE BY ILLICIT DRUG USERS

The aim of our study was to obtain some more representative data on the use of benzodiazepines by illicit drug users than was available from previous work on selected populations. To do this we turned to data that were available on all problem drug users presenting to the range of treatment agencies within one UK health region, i.e. the information provided to the North Western Regional Drug Misuse Database. The repc:rting system to this database incorporates the Home Office notification of addicts which is requiredby law in the UK, but extends far beyond this in three important ways. First, details are collected, on the standard reporting form which covers a period of one month before interview, of the use of all drugs and not solely the drugs which are designated as notifiable under the Home Office system; secondly, forms are completed not only by doctors but by the other workers to whom problem drug users present at the range of drug agencies; and, thirdly, in addition to details of drug use, information is collected on a wide range of demographic and social factors, and on service usage. This paper contains data on prevalence and on some aspects of usage patterns, whereas a more detailed analysis of similar data from a later time period is to be separately published.

The Drug Misuse Database reporting system has been described by its devisor and forms the basis for the system that is being implemented nationally in the UK (Donmall, 1990). Once again in this paper it is not possible to discuss more detail, but it is important to say that it is requested that forms are completed on all individuals who are considered by workers to be problem drug users either newly presenting or after a gap of 6 months to a treatment agency; these agencies include all the community drug teams, the Regional Drug Dependence Service, the largest of the non-statutory drug organisations, general practitioners, hospital outpatient and in-patient services and accident and emergency departments, and police and prison medical services. The system is anonymous but a method is incorporated to avoid double counting of individuals. In order to investigate the use of benzodiazepines by illicit drug users, we defined an illicit drug user as any individual who was taking any drug that was not prescribed to them, and we also included in that definition any individual taking methadone, the rationale being that in this population methadone treatment almost certainly signifies involvement at some stage in illicit drug use. The study covered the first reports of individuals to the database in the 2-yearperiod 1988 and 1989.

TABLE 1: Prevalence of benzodiazepine use among illicit drug users: total and analysed according to main drug

Excluding 118 whose main drug was a benzodiazepine:
X² = 115.82, d.f.=9, p<0.001
ª Dihydrocodeine, dextromoramide, buprenorphine etc
º Major tranquillisers, antidepressants etc

The prevalence of benzodiazepine use by illicit drug users is presented in Table 1, both in total and then by dividing the population according to their main drug of use, which is identified on the reporting form. It can be  seen that approximately 16% of the 4213 drug users reported to the database in this period were using benzodiazepines. This is a much lower figure than that found in previous studies, which is no doubt primarily due to the much more widely representative basis of this study. A finding that we felt had substantial implications was the high rate of use of benzodiazepines among those whose main drug was either methadone or other opiates such as dihydrocodeine, dextromoramide or huprenorphine. This contrasted with much lower rates of usage of benzodiazepines among users whose main drug was'street'heroin, amphetamines or cocaine, and, because methadone and other opiates are categories of drug that are often likely to have been prescribed as a treatment, the figures suggested to us that benzodiazepines may frequently represent an additional prescribed accompaniment to a methadone orotheropiate prescription. From the database information we know whether drugs have been prescribed or not, and so we were able to test this theory indirectly by comparing the use of benzodiazepines in those whose main drug was prescribed or non-prescribed.

In Table 2 there is a comparison of main users of prescribed and non-prescribed opiates and there is a clear demonstration that the former group are much more likely to be using benzodiazepines. In most cases it is known from the database information whether nonmain drugs such as the benzodiazepines have been prescribed, and the second part of the table further demonstrates that the benzodiazepines themselves have been prescribed much more often in the case of users of prescribed opiates than of users of non-prescribed opiates. Although these figures are cross-sectional and do not identify the same individuals at different stages in a drug-using career, the comparisons that we made seemed to suggest that those individuals who enter treatment and receive an opiate prescription may also frequently receive benzodiazepines from anew even if they have not been using these in their 'street' drug use.

In Table 3 is presented some information on the patterns of usage of benzodiazepines by the subjects in this study. Although most previous studies have identified diazepam as the main benzodiazepine used even by illicit drug users, it has become apparent in recent years in the UK that temazepam is extremely popular with this group, partly because of its formulation as a liquidfilled capsule whose contents can be injected. These data provide the first large-scale confirmation of this phenomenon, although it can also be seen that twothirds of the illicit drug users who are using temazepam are apparently taking it orally only. In this country, in response to the use of temazepam by injection, the capsules have been re-formulated to contain a thicker gel material. It is not yet clear what overall effect this has had on the rate of injecting, but it is certain that injecting of the new style contents, after liquefaction through heating, is still widely practised and this may even be more harmful in some cases. It is our general clinical impression that widespread conversion of prescriptions to the tablet form of temazepam has not taken place in this population, although it can be seen from the study data presented that the other benzodiazepines in tablet form are very rarely injected.

A detailed analysis of dosages of benzodiazepines used is not contained in this paper and will be presented in a subsequent study. Two points, however, may be made here which are known from the study data available at this stage. The first is that by no means all illicit drug users take their benzodiazepines in high dosage, with large numbers being reported as using the various drugs in ordinary therapeutic dosage. The second is that at the top of the range a proportion of users have escalated their dosage to five to fifteen times the maximum therapeutic dosage,and the highest daily usage of each of the three most frequently used benzodiazepines is contained in the table. The highest escalation of dosage was evident in the case of temazep-am, a finding also demonstrated in a clinical study, recently undertaken in this area, of individuals who had experienced withdrawal symptoms after high-dose usage of benzodiazepines (Seivewright and Dougal, 1993).

TABLE 2: Prevalence of benzodiazepine use in main use in main users of prescribed and non-prescribed opiates, and proportions in whom those benzodiazepines were prescribed

SOME PRINCIPLES AND PROBLEMS IN THE MANAGEMENT OF BENZODIAZEPINE USE BY ILLICIT DRUG USERS

In turning to the management of benzodiazepine use by illicit drug users, often in the context of polydrug use, the last part of the data presented above is immediately relevant. A wide range of patterns of usage and dosages is encountered, and there may be virtually no similarity between the management of a regular night-time prescription of nitrazepam for sedation, and that of highdose injected use of temazepam. However, a brief discussion of some of the main principles involved and some of the most common problems and dilemmas encountered in the treatment situation would seem to be indicated in view of the lack of published guidance apart from some studies of in-patient detoxification. Most of what follows derives from the clinical experience of those two of us who work in a treatment service, although it must also be pointed out that this necessarily brief discussion will concentrate primarily on the merits and demerits of prescribing benzodiazepines ir management situations. Different problems arise in the cases of in-patient detoxification and longer-term outpatient management and these will be considered separately.

TABLE 3: Benzodiazepines used by illicit drug users, route and maximum daily dose

IN-PATIENT DETOXIFICATION

This is definitely the less problematic of the two areas but nevertheless it still has its pitfalls. The first point of importance is that it is usually highly desirable to prescribe in the detoxification situation to a user who has been using significant amounts of benzodiazepines prior to admission. This may appearobvious, but there are certainly detoxification units whose policy includes a methadone detoxifcation for opiates but would not include benzodiazepines, and in the wider context of police custody and prison benzodiazepines are of course very frequently withheld. In recent years there has been some pressure from drug agencies upon authorities for the provision of a humane methadone detoxification 1 programme to opiate users in custody, but the a is probably stronger in the case of benzodiazepines, where more dangerous withdrawal symptoms such as epileptic fits may occur. In all settings problems arise in judging reliability of information about drug usage, but these difficulties are not confined to the benzodiazepines and will not be discussed here.

In-patient detoxification from benzodiazepines is probably one situation in which managernent~ can appropriately he based upon the very substantial body of evidence that exists from studies of low-dose sole users. The basis of this is the conversion of an individual's average benzodiazepine intake to an equivalent dose of the long,acting benzodiazepine diazepam, followed by a reduction in dosage over a period, that aspect being advisedly negotiated with the individual concerned. The dosage conversion itself very frequently raises a practical problem in that conversion from the extremes of 'street' usage, especially of emazepam, can seem to indicate a need for a starting dose of several hundred milligrams of diazepam. For various reasons it appears, fortunately, that such doses are hardly ever required, and our experience on adetoxfeation unit, where we consider it a priority to avoid patients experiencing severe withdrawal symptoms, is that starting doses of diazeparn can usually be kept below 100 mg/day. In a study of detoxification from high-dose benzodiazepine use in 23 subjects, Harrison et al. (1984) found that a diazepam equivalent starting dose of 40% of reported daily consumption followed by daily tapering by 10% ensured satisfactory completion of detoxification in the majority of cases, whereas Scott (1990) claimed that a detoxification using 60 mg diazepam reducing in 10 mg steps each day to zero over 6 days led to no convulsions occurring even in a group who had had a high incidence of these during previous enzodiazepine withdrawals.

In a harm-reduction approach to clyug addiction it is essential that a realistic appraisal is made of the likelihood of relapse after any detoxification. The rate of relapse 1 year after in-patient detoxifcation from opiates may be as high as 97% (Valliant, 1988), and we can see no compelling reason why the rate of relapse in benzodiazepine use by illicit drug users should be substantially different. Although there are no doubt some drug users for whom the use of benzodiazepines is something of an optional extra, there are many others who are highly dependent upon benzodiazepines both psychologically and physically, and it is a matter of common clinical experience to encounter an indivi ual in a detoxification unit who appears reasonably happy about the prospect of living without opiates but is much more apprehensive about managing without benzodiazepines which he or she may have been taking for many years, sometimes even since childhood. In recognising the general need to treat individuals at all levels of motivation and to accommodate a range of acceptable goals, apart from complete abstinence from drugs, we need to consider the management of benzodiazepine use in situations other than a relatively straightforward in-patient detoxification.

LONGER-TERM OUT-PATIENT MANAGEMENT

This is the point at which the literature concerning management of benzodiazepine dependence in lowdose sole users begins to appear increasingly unrelated to our needs in working with a very different population. Even though many illicit drug users appear to be taking benzodiazepines in approximately therapeutic dosage, the treatment options suitable for low-dose sole users such as support groups, psychological therapies, and adjunctive drug treatments such as propranolol or dothiepin, are ones in which many illicit drug users would be very unlikely to engage satisfactorily. On the other hand, many aspects of the management of betizodiazepine use by illicit drug users should be those that are applied to any situation of polydrug use, and evidence has already been referred to that underlines the need for harm reduction and safe practices advice in these users. In devising a total harm-reduction package, however, sooner or later one must consider the possibility of prescribing and it is this aspect that we would like to examine in a little more detail. The role of prescribing in harm-reduction programmes foropiate users is firmly established and widely identified as a priority strategy, but there is no such consensus regarding the prescribing of any other group of substitute drugs. In considering the possible role of the prescribing of benzodiazepines in a substitute programme we may examine why that is. First, however, due emphasis must be given to the disadvantages, sometimes substantial, of prescribing benzodiazepines to illicit drug users.

TABLE 4: Rationales for prescribing substitute drugs in the longer term to illicit drug users

The general pitfalls in prescribing any medications to drug users, such as ascertaining accurate information on extent of usage, the forming of treatment agreements and the avoidance of diversion of supplies to other individuals, cannot be considered in detail here. In relation to benzodiazepines in particular, it should be pointed out that these drugs are not included in the stringent controls that apply to the writing of prescriptions for drugs such as methadone, and it is therefore administratively much easier for a doctor to issue a prescription for benzodiazepines than one of the higher category controlled drugs. Virtually nobody would dispute that benzodiazepines are hugely over-prescribed, and it is difficult not to envisage a situation in which benzodiazepines may often be prescribed to illicit drug users by, say, general practitioners as a kind of compromise, in which something positive is being done without the complications inherent in prescribing   methadone; this situation may come about with or without pressure on behalf of the drug user. Insomnia is
an effect or a withdrawal effect of many of the illicit drugs and it is probably common for benzodiazepines, notably temazepam, to be requested for that reason but then used differently, often by injection. We may consider again the data presented earlier which suglested that the prescription of benzodiazepines may often rep
resent a new additional drug rather than a treatment substituting for previous illicit use, and many would consider this to be nearly always inadvisable. Finally, even at the most informed level, there may be reservations about prescribing benzodiazepines to an individual, substantially using illicit supplies, if it is suspected that they are being used to enhance the effect of opiates, which subjectively appears common.
Partly by indicating the kinds of cases in which it is usually not advisable to prescribe benzodiazepines, we have, however, begun to imply that there may be contrasting situations in which an argument could be made for the use of a prescription of benzodiazepines as a harm-reduction measure, perhaps in particular to substitute for illicit problematic use for reasons similar to those for which methadone is used in opiate users. In a short space it is impossible to consider separately the range of clinical situations in which such an intervention might appear appropriate, or to make any more than passing reference to the paradox of even considering longer-term prescribing of benzodiazepines when the remainder of psychiatric services are trying assiduously to remove their much more stable low-dose users from those drugs, and we will confine ourselves finally to a brief theoretical examination of the prescribing option. We have attempted in Table 4 to summarise the reasons whythere isbroadly aconsensus infavourofthe prescribing of a substitute opiate drug, usually methadone, as a longer-term strategy to some opiate users, but no such consensus in favour of such a role for substitute prescribing of amphetamines or of cyclizine, widely used by illicit drug users in several areas of the UK.

Certain arguments could be made in favour of a prescription of any of those, based upon the likelihood of continued obtaining of illicit suppi ies if a prescription is not provided, and the attraction into treatment services. However, on the whole substitute prescribing is only widely supported in the case of drug groups that exhibit definite physical dependence, that do not produce an inherently de-stabilising effect (which can be levelled at amphetamines and cyclizine), and that contain at least one candidate which is longer acting and therefore may be more stabilising. If the benzodiazepines are included in the same analysis, it would appear that a reasonable case may be made for prescription in this group of drugs for similar reasons to those accepted in the case of opiates. The advantages may appear theoretical rather than practical, but it has to be faced that the prescribing option is in the forefront of harm-reduction approaches for opiate users, and furthermore that successful engagement in such programmes can be hampered if prescribing is ruled out. It REFERENCES is probably reasonable to suppose that there are drug Busto, U., Sellers, E.M., Narango, C.A., Cappell, users using benzodiazepines harmfully who would achieve increased stability and derive certain advantages if a benzodiazepine were prescribed, although there are others in whom prescribing would be a retrograde step and cause more problems than would be alleviated. More study is required of many aspects of the phenomenon of benzodiazepine use by illicitdrug users, including detailed information regarding patterns of usage, before clinical advice relating to different subgroups of this population can be formulated.

In view of the potential disadvantages of prescribing benzodiazepines, and in particular of prescribing emazepam, in this population, it is appropriate to end with reference to another treatment strategy which has apparently been effective. In an unpublished clinical study of 23 injecting users of opiates and temazepam, Ruben and Morrison (1992) found that many of their ubjectsclaimed to be able tostop injecting temazeparn when their treatment for opiate dependence was converted to the injectable form of methadone. Clearly that strategy is one which could only be appropriately managed in a specialist treatment clinic, and will require further study before definite effectiveness can be claimed, but it is a good example of the kind of realis, tic approach to the cases at the more severe end of the spectrum of benzodiazepine use amopg illicit drug users which is required in treatment thit incorporates the principles of harm reduction.

Nicholas Seivewright is the Senior Lecturer in Drug Dependence, University of Manchester Department of Psychiatry; Michael Donmall is the Director, Drug Research Unit, University of Manchester Department of Public Health and Epidemiology; Christopher Daly is the Senior Registrar in Psychiatry, Manchester Royal Infirmary.

References

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