Phannacotherapy in the Treabnent of Drug Dependence: Options to Strengthen Effectiveness Sarah Welch & John Strang

Advances in Psychiatric Treatment (1999), vol. 5, pp. 427-434

Phannacotherapy in the treabnent of drug dependence: options to strengthen effectiveness Sarah Welch & John Strang

Treatment ofpeople with drug problems requires a consideration of those inviduals in their personal Dependence andsocialcontext, whilebeingmindfulofthecomplex interactionofgeneticand developmental influences. Approaches to treatment should reflect this often Identifying the presence or absence of the depen• complex aetiology and phenomenology, and the dence syndromeis importantin planning treatment. totality of treatment will typically include social, Dependence is a spectrum, and the therapist needs psychological, educational and pharmacological to developexperience in recognising degrees ofsever• therapies. Treatment should result in a health benefit; ity. The dependencesyndromeis a clusterof physio• consequently thegoals oftreatmentshouldbetailored logical, behavioural andcognitive phenomena (leD• to the health care needs ofthe individual. Thus, with 10; World Health Organization, 1992; see Box 1). many patients, treatment will includeabstinence as Apart from the management ofoverdose, which an explicit objective, whereas with other patients, may, ofcourse, affect those who misusedrugs only intermediate goals, such as reduction of harmful once, the majority of pharmacotherapies are injecting, maybe more realistic and achievable. designed for use by those who have, or have had, Enthusiasm for new pharmacotherapies mustbe some or all of the features of the dependence syn• tempered withcaution. Thefield ofsubstancemisuse drome. These include drugs used for the manage• standsasanexamplepar excellence ofanarea inwhich mentofwithdrawal; substitute pharmacotherapies careless use of pharmacotherapy may compound used as partofa harm-reduction programme;drugs problems for the individual patient (e.g. iatrogenic used to help maintenanceofabstinence from alcohol benzodiazepinedependenceafter failure to review or other substances; and drugs used to prevent repeatprescriptions) as well aspossibly for others (e.g. specific complications of substance misuse. danger ofoverdose orofhuman immunodeficiency virus (HIV) infection from intravenous misuse of diverted pharmaceuticalopiatesorbenzodiazepines). In this paper, wewill first discuss the dependence Pharmacotherapies in the syndrome, which the clinician crucially needs to management of drug overdose understand and examine, since several of the treat• ments described in the remainderofthis papermay be inappropriate or even contraindicated in the Benzodiazepines absence ofdependence. Thereafter, five main areas of potential action of pharmacotherapies are Mortality from overdose with benzodiazepines considered separately. alone is rare, althoughoverdose in conjunction with

Sarah Welch is a Consultant Psychiatrist in the Addictions, South London and Maudsley NHS Trust, and Honorary Senior Lecturer, Institute of Psychiatry. She works with drug and alcohol users in the local services, and teaches for the Institute's MSc in Clinical and Public Health Aspects of Addiction. John Strang is Director of the National Addiction Centre (4 Windsor Walk, London SE5 8AF) and Clinical Director of the Drug and Alcohol Services at the Maudsley and Bethlem Royal Hospitals. He has published more than 200 papers and book chapters in the addictions field, and has edited four books on the subject. Box 1. Dependence yndrome - a clu ter of physiological, behavioural and cognitive phenomena (JCD-10; World Health Organization, 1992)

trong de ire or compul ion to take the ubstance DifficuJtie in controUing ubstance-taking behaviour in terms ofits on et, termination or levels of u e phy iological withdrawal tate when ub tance u e ha cea ed or been r duced, as evidenced by: the characteri tic withdrawal yndrome for the sub tance; or use of the arne (or a closely related) ubstance with the intention of relieving or avoiding withdrawal symptoms vidence of tolerance, uch that increa ed do es of the p ychoactive ubstance are required in order to achieve effect originally produced b lower do e Progre ive neglect of alternative plea ure or interest becau e of p ychoactive sub tance u e, increa ed amount of time nece ary to obtain the ub tance or to recover from its effect Per i ting with ub tance u e de pite clear evidence of overtly harmful consequences otherdrugs, such asopiatesor tricyclic antidepres• severe cases, mechanical ventilation may be sants, carries a higherrisk. As for alcohol poisoning, necessary. After the administration of naloxone, management is generally supportive. However, the opiate-dependent patients will experience acute benzodiazepine antagonist flumazenil may be withdrawal. This can be a difficult period as it is useful in both the diagnosis and the treatment of important to continue to observe the patient for at overdoses in which benzodiazepines are involved. least 24 hours, butdiscomfort maycause the patient Flumazenil binds central nervous system benzo• to leave early to seek moredrugs. Hit is considered diazepine receptors and competitively blocks the that the patient maybe at risk ofreturn tooverdose action ofbenzodiazepinesat inhibitoryGABAergic as the naloxone wearsoff, it maybe appropriate to synapses. A single injection of 0.1-0.3 mg may be give an additional dose intramuscularly. If the given, with further increments if needed until the patient has taken an overdose of oral opioids but patient is responsive (Weinbroum et aI, 1997). Higher does not yet show signs of impaired consciousness dosesmaybeneeded inoverdosesofbenzodiazepines or respiratory depression, activated charcoal canbe with otherdrugs. Adverseeffects are uncommon but given and the patient observed closely, with mayincludebenzodiazepinewithdrawal symptoms readiness to treat with naloxone ifneeded. with transient anxiety. Care should be taken with patientswithcardiovasculardisease. Rarely, seizures Stimulant and hallucinogenic may occurand may be more likely in patients who drugs are benzodiazepine-dependent and in those with concurrent tricyclic antidepressant poisoning. Cocaine and other stimulants such as ecstasy (MDMA) and amphetamines can induce euphoria Opiates oranxiety which may proceed to moreseveresymp• toms such as paranoid ideation, aggressive behav• Opiate overdose produces pinpoint pupils and iour and hallucinations. Management involves varying degrees of impairmentofconsciousness and calming and reassuring the patient until the effects respiratory depression. The opiate antagonist wear off. Occasionally, oral diazepam (10-20 mg) naloxone, which is available in pre-loaded syringes may beneeded to help calm thepatient, andinsevere for use in emergency settings, should be admin• cases where symptoms persist, antipsychotic istered intravenouslyif there iscoma orbradypnoea. medication maybeneeded. Rarely, cocaineoverdose The dosage is 0.8-2 mg, and this may need to be can result in cardiovascular complications includ• repeated at intervals of2-3 minutes to a maximum ing arrhythmia, hypertensionandcardiacischaemia. of10 mg if respiratory function does not improve. H Seizures and hyperpyreXia can also occur. In such thereare problems with establishing venous access, cases, treatment is supportive (LobI & Carbone, naloxone may be administered intramuscularly or 1992) - there are no specific drugs used to reverse subcutaneously. Naloxone has a short duration of the effect ofcocaine. action, and particular care needs to be taken if the Some peopleexperienceseveredistressduringor patient has taken a long-acting opioid such as after use of hallucinogenic drugs and may need methadone (Hendra et aI, 1996). In such cases it symptomatic treatment (such as a brief course ofa may be necessary to set up a naloxone infusion benzodiazepine to reduce anxiety) as well as a safe which can be adjusted according to response. In place to be while the experience passes. / '/111/ ; 1/1/ [ 1/ II /[ ; tll'll , III/II tI J 1I'~ I II I II III/I 1/ (I \ I) /(/'l'I'i), , I' I ), I I, -+ ~ 'i

Overdose prevention Opiates

Certain factors are thought to putdrug and alcohol Traditionally, withdrawal from opiates has been users at higher risk of overdose. Among these are managed byprescribing tapering doses ofeither the polydrug use (including combining alcohol with opiateofdependenceor, alternatively, anotheropiate other drugs); use of unfamiliar supplies of drugs agonist. The choiceofopiate for managementofthe where purity is unknown; the intravenous route of withdrawal state is determined partly by the clin• administration (presumablybyreducing thechance ician's judgement on the most suitable drug for of titrating dose against effect); and use of drugs providingevencover, partlybytheexpressed wishes aftera period ofabstinenceor reduced use (such as ofthe patient, and partlyby the social and political after leaving residential treatment facilities or context within which the treatmentis provided. For leaving prison) (Gossopet aI, 1996; Darkeet aI, 1996). example, diamorphine (heroin) is never prescribed Opportunitiesfor preventiveworkin termsofadvice as the drug for management of the withdrawal and education for drug users can, therefore, be syndrome - largely because of the sense of public identified. This could extend to teaching basic outrage thatwould beengendered (indeed, prescrib• resuscitation techniques. The possibility ofissuing ingofthe drugis entirelyprohibited for any purpose injectable naloxone to drug users for use in whatsoever in manycountries, such as the USA; its emergencies (Stranget aI, 1996a; Darke& Hall, 1997), use in the UK is restricted to clinical indications an idea which drug users regard as acceptable and other than the management of addiction, except feasible, has been proposed as a harm-reduction when prescribed by one of the 100 doctors with a measure (Strang et aI, 1999). special heroin licence). The mostcommonlyselected opiate, methadone, is considered moreappropriate because it is effectively and reliably absorbed after Pharmacotherapies for drug oraladministration, and gives anextended duration ofcoverso that twice-dailydosing gives good cover withdrawal syndromes against the moreextremeaspects ofthe withdrawal (detoxification) syndrome. It has now been demonstrated that the withdrawalsyndromecanbemanagedaseffectively, and with similar compliance rates, with a shorter Benzodiazepines 10-day withdrawal regime compared with the previously widely used 21-day withdrawal regimen Benzodiazepine withdrawal symptoms are due to (Gossopet aI, 1989). However, theextensive reliance unopposed activity of the 'Y-aminobutyric acid ontheout-patientsettingfor themanagementofsuch (GABA) complex. They include anxiety, tremor, withdrawal is probably ill-considered inviewofthe tachycardia, tachypnoea, nausea, abdominalcramp, much higherfailure rate ofthis approachcompared skeletal musclecrampanddiarrhoea. In moresevere with in-patient detoxification (Gossop et aI, 1986). cases, perceptual disturbances and seizures may Furthermore, the setting in which the treatment is occur. The different benzodiazepines have a wide provided appears to have a profound effect, with range of half-lives which affect the pattern and muchgreatercomplianceand completion rates being severity ofthe withdrawal syndrome. Temazepam seen when detoxification is provided within is a short-acting benzodiazepine, oxazepam and specialist in-patientservices compared withgeneral nitrazepam have intermediate half-lives, and psychiatric ward settings (Strang et aI, 1997a). diazepam is longer-acting. Onset of withdrawal Since the 1980s, increased attention hasbeen paid symptoms from short-acting benzodiazepines is to non-opiatealternatives to managementofdetox• rapid, whereas the onset of withdrawal from ification. Clonidine,a centrally-acting a-adrenergic diazepam is more insidious, sometimes beginning agonist, was extensively investigated (Kleber et aI, days after the last dose of diazepam. Management 1985) and shown tobeeffective, although themarked ofwithdrawal involves gradual tapering ofthedose postural hypotensiveeffects ofthedrugare usually - in out-patients this is usually planned over the considered to limit its application to in-patient courseofseveral weeks (Lader& Morton, 1991). For settings. More recently, successful outcomes have individuals using short-acting benzodiazepines, it been reported with lofexidine, a clonidineanalogue is usual to change over to an equivalent dose of which is notassociated with hypotension to thesame diazepam for the purpose of withdrawal, as its extent as clonidine (Beam et aI, 1996; Kahn et aI, longer action allows a smoother reduction. For 1997), and which has been found to be acceptable patients with an established history of seizures, for out-patient detoxification under supervision concomitanttreatment withananticonvulsant drug (Carnwarth& Hardman/ 1998)(see Box 2). Other, more is advisableduring and shortly after detoxification. extreme treatment approaches are being explored in an attempt to shorten further the duration of the withdrawal syndrome; these approaches include Bo 2. t pical lofe idine regime for combination pharmacotherapiessuch asclonidine/ treatment of opiate withdrawal naloxone (Vining et ai, 1988), and delivery of high doses of antagonists (naloxone, naltrexone) in umber of 200 J.1.g tablet combination with general anaesthesia or heavy am pm sedation. However,·the effectiveness of these Day 1 1 2 approaches has not been investigated in rigorously Day 2 2 3 designed trials and their use should be considered Da 3 3 4 only in the context ofcarefully designed treatment Day4 5 5 trials (Strang et ai, 1997b). Da 5 5 5 Da 6 5 5 Stimulant and hallucinogenic Da 7 4 4 Oa 3 3 drugs Da 2 2 Oa 1 1 Stimulant drugs such as amphetamines, cocaine and ecstasy do not produce a major physiological onitor pul e and blood pre ure regularly withdrawalsyndromeand can bestopped abruptly. However, people who have used stimulant drugs regularly may experience insomnia and depressed mood when the drug is stopped. Antidepressant drugsaresometimes used, butmanystimulant users their supply is abruptly unavailable, since the just need advice regarding the likely symptoms, and withdrawal syndrome can be severe and may reassurance that they will pass. Occasionally, involve seizures. Benzodiazepines are widely patients may become acutely suicidal and will available through illegal outletsand can bebought require hospital admission and close observation. cheaplybydrugmisusers. Many will usethese drugs Hallucinogenic drugs such as lysergic acid inan intermittent, non-dependent fashion and there diethylamide (LSD) do not produce a physical is no role for substitute prescribing. For those withdrawal syndromeand can bestopped abruptly. individuals whoare using 'street' benzodiazepines Thereis no recognised role for substitute prescribing in a dependent fashion, prescribing of benzodiaz• in the management ofwithdrawal. epines may beappropriate,although again this will usually be with the aim of dose reduction and withdrawal. In contrast to methadone prescribing, there is little evidence that continuous substitute Substitution agonist therapies prescribing is helpful as the harm-reduction gains are less clear than for methadone. Nevertheless, Benzodiazepines such regimes maysometimesbeagreed withcertain patients ifthere are demonstrable benefits.

Cross-tolerance has been demonstrated between the barbiturates, alcohol, the benzodiazepines and the Opiates newer non-benzodiazepinesedative hypnotic drugs which have recently been more widely used, such The most extensively studied and applied agonist aszopiclone. Long-term benzodiazepinedependence therapy is oral methadonemaintenanceas treatment might be reduced if drugs with shorter half-lives for heroin addiction (see Boxes 3 and 4). Atanyone were prescribed for night sedation, which allows time, there are of the orderofa quarterofa million clearanceofthe drugbefore the nextdose. However, opiate addicts being treated with oral methadone it is not established whether this would have any worldwide. Even though there hasbeen a surprising effect at the population level. For those who have shortage of randomised controlled trials of the becomedependenton prescribed benzodiazepines, treatment (Ward et ai, 1992), there is robust evidence initiation ofa long, slow dose reduction (see section ofmajorbenefitsacrossa variety ofoutcomedomains on withdrawal) is probably thebest course ofaction, - reduced illicit drug use, reduced injecting, reduced rather than continuing 'maintenance' prescribing. involvement in crime, and improved physical and However, in practice, somepatientswho have been social well-being (Marsch, 1998) - with these major prescribed benzodiazepinesfor many years find this benefits being seen even within the first month of prospect very distressing and maintenance pre• treatment (Strang et ai, 1997c). The recognition ofthe scribing is continued. Such patients are at risk if particular importance of reduced injecting and 1 / )11111'111111 "IIIt 1 II/ I 11" IIIIt I I 11 /I'~ I II '/ II 111 It III I' \ I) I ( 1'/'1 )), ,'I'I, ." / I, -+ j I

sharing as anHIV preventionstrategy have prompted the developmentand further expansion ofstructured Box 4. Pre cribing methadone safely oral methadone maintenance programmes in many countries. Initial dose titration and con umption hould Although methadone gives good 24-hour cover usually be upervised by a doctor, nurse for the majority of patients, there has been interest or pharmacist in developing similar agonist drugs which would The dose can be titrated against continuing providea longer duration ofcover. The most promis• observed withdrawal ymptoms, to deter• ing candidate hasbeen LAAM which, as a pro-drug, mine a safe and comfortable dose does not have a sudden intoxicating effect and yet Methadone hould usuallybe prescribed in provides good cover over a period of 2-3 days, a liquid form, as tablet can be crushed thereby making possible supervised dosing sched• and injected ules on a MondayI WednesdayI Friday basis (Ling For rno t patient, methadone should be et aI, 1994). Similarly, exploratory work is currently dispensed on a daily ba i underway with high-dose buprenorphine, although A clear prescribing and dispensing record it remains to be seen whether it will be possible to must be kept avoid the problem of extensive intravenous misuse Treatment hould be reviewed regularly ofbuprenorphineas encountered and reported from several UK cities (Hammersley et aI, 1990). Injectable agonist substitutes have been prescribed in the UK for some time (Strang & Sheridan, 1997a). as treatment for cocaine oramphetamineaddiction. The value ofthis practice was recently explored in a Reports ofsuch practice in the UK from the late 19605 study in Switzerland (Perneger et aI, 1998). While (Hawkset aI, 1969; Mitcheson et aI, 1976) were gener• attention mostly focuses on the feasibility and ally accounts ofmanagement complications and lack possible benefits of injectable heroin prescribing of therapeutic benefit. Nevertheless, more recent (Bammer, 1993), it is injectable methadone which is clinical reports in the UK (Fleming & Roberts, 1994) the most commonly prescribed injectable agonist in have described clinical experiments with this the UK (Strang et aI, 1996b). Such injectable prescribing approach, which had been found to be more wide• remains the subject of continued heated debate, and spread in practice than previously recognised should only be considered as a more complicated (Strang & Sheridan, 1997b). treatment for carefully selected patients under the care of specialist centres. Relapse prevention and the Stimulants maintenance of abstinence There is no substantial body of evidence or experi• ence on the prescribing ofsubstitute stimulantdrugs Psychological and social interventions are the main• stays of relapse prevention in the management of patients with drug problems. Relapse prevention work, carried outonanindividualorgroupbasis, takes Box 3. ub tHute prescribing ofmethadone a cognitive-behavioural approach towards iden• tifying vulnerability to lapses (intrapersonal states Before beginningprescribing of methadone, such as loneliness or anger; interpersonal states the doctor should establish the following: such as conflicts or fear of social situations; and • that the pati nt is using opiates (hi tory, peer pressures) and looking atalternative strategies examination, urine drug creen) for coping with these situations (Marlatt & George, • that opiates are being used daily oralmost 1984). Social interventions may include changes in daily occupation, and housing. Couple therapy orfamily • that there i convincing evidence ofdepen• therapy may behelpful. Although mostly designed dence (including evidence of withdrawal to help patients to maintain abstinence, these symptoms where po sible) approaches may bealso be adapted to help patients • that the a e ment ub tantiate the need with other goals such as reduced orsafer drug use. for treatment A number of pharmacotherapies are used in • that the patient is willing to cooperate with conjunction with these techniques. The pharmaco• a pre cfibing regime therapies are generally aimed at those patients intending to maintain abstinence. APT(1999), I'ol. 5,p. 432 Welcll & Stl'l1l1g

Maintaining abstinence from whichthehealthgainmaybemaximised. Insituations opiates wheretheexclusivepursuitofabstinence maymerely lead to high ratesoftreatmentfailure and drop-out Naltrexone (possibly withevenmorecatastrophic consequences due to the abstinence violation effect (Marlatt & Naltrexone isa long-actingcompetitiveantagonist George, 1984», there willbecircumstancesin which at opioid receptors. It is suitable for oral adminis• theidentification ofmorerealistic intermediategoals tration, and as it blocks the effects of opiates (both maylead togreaterindividualand publichealth gain subjectiveand objective) it canbeused asanadjunct (Advisory Council on the Misuse of Drugs, 1988; to the management of opioid dependence, for Strang 1990). This acceptance of the seemingly im• patients whoaim to maintain abstinence. It is well• perfect has undoubtedly led to greater health gain, tolerated bymostpatients, witha minority experien• with the establishment of advertising and peer cing headache or nausea. Patients will only take network schemes for the dissemination of infor• naltrexone regularlyiftheyarecommitted toabstin• mation about syringe cleaning, needle and syringe enceand haveanincentive tostayabstinent. Itshould exchange schemes, as wellas the substituteagonist be combined with individualorgroupcounselling, programme described in the preceding section. and the best results are seen when it is provided in These remain areas of dispute and debate among conjunction withfamily involvementandcontingent practitioners themselves and between practitioners rewardsasinthe'communityreinforcementapproach' and policy-makers. Harmreduction areasofcontin• currently under study. The search for a depot form ueddebatealso include proposalsfor theprevention of naltrexone has not yet produced a product with ofoverdosedeaths through the teaching ofresuscit• acceptablesafetyand reliability- furthermore, it may ation techniques to known drug misusers, possibly lead to a failure to recognise the importance of the supplementedbytheprovisionoftake-homesupplies psychosocial context in which such a pharmaco• oftheopiateantagonist naloxone (Stranget ai, 199(0). therapeutic approach might bedelivered. Hepatitis B testing and vaccination Maintaining abstinence from stimulant drugs Markers of past hepatitis B infection are found in mostinjecting drug misusers, prevalence rates vary• ing between half and three-quarters, depending on No pharmacotherapies have been clearly shown to thesample. Around 10% will havechronic infection reduce the rate ofrelapseamong users ofstimulant with hepatitis B, a large proportionofwhomwill die drugs. A varietyofantidepressantdrugs have been prematurelyfrom eitherlivercirrhosis orhepatocel• used, buttheirsustained effectiveness in preventing lular carcinoma in their later lives. Furthermore, in relapse is not strongly supported by research the intervening years, they may transmit the virus evidence. Psychological andsocialapproachesremain either by sharing injecting equipment or by sexual the mainstay oftreatment for stimulant misusers. transmission to their partners and thence to their children. Since thedevelopmentofsafeandeffective vaccines, the condition is now entirely preventable Prevention of complication for those who are not yet infected, and the World drug Health Organization has identified as a priority the of misuse eradication ofhepatitis B through universal vaccin• ation. The injecting drug misuser should be offered The scope of harm reduction testing for hepatitis B and, if negative, hepatitis B vaccination: themanufacturers recommend a dosing schedule of 0, 1 and 6 months for the three vaccine The principlesofharm reduction havecometo exert injections, buta dosingscheduleof0, 1and 2 months a powerful influence upon the developmentofdrug may be more realistic so as to capture the drug user policy following the recognition ofthe risk posed by during an episode oftreatment, especially since the HIV infection and transmission (Strang, 1992). The benefitconferredbythis quicker vaccination protocol harm reduction approach is essentially a public is almostas full as with the recommended schedule. health approach which proposes that public policy and treatments should be based on an analysis of optimal reductionofharmfor thepopulationin treat• Antiretroviral therapies for HIV • ment(or the populationwith health need, evenifnot post-exposure therapy currently in treatment). Hence, abstinence is not the essential objective of treatment; rather, it is more The adventofnewantiraetroviral therapies for treat• appropriately considered as one of the ways in ment ofHIV infection has increased the possibility /)/ill JJ1I11 ( (, tJ I ( J 1I / 'I ( , (III, I(I J 1I'~ (I ('I ,( iI,{( II ( I \/)/(/

oftreatment of individuals thought to have been at - & Hall, W. (1997) The distribution of naloxone to heroin users. Addiction, 92, 1195-1199. riskofvery recent infection. For example, this could Fleming, P. M. & Roberts, D. (1994) Is the prescription of includethetreabnentofmedica1ornursingstafffollow• amphetamine justified as a harm reduction measure? ing a needle-stick injury from an infected patient. It Journal of the Royal Society of Health, 114, 127-131. Gossop, M., Johns, A. & Green, L. (1986) Opiate withdrawal: increases the possibility ofuse ofsuch therapies for inpatient versus outpatient programmes and preferred injecting drug misusers who have, for example, versus random assignment to treatment. British Medical recently shared a needle with an infected person. Journal, 293, 103-104. -, Griffiths, P., Bradley, B., et al (1989) Opiate withdrawal The recurrent treatment ofdrug misusers whoare at symptoms in response to 10-day and 21-day methadone constant risk is impractical, but there may be withdrawal programmes. British Journal of Psychiatry, 154, arguments for its use under certain circumstances. 360-363. -,-, Powis, B., et al (1996) Frequency of non-fatal heroin Caution must, however, beexercised. withcombin• overdose: survey of heroin users recruited in non-clinical ation pharmacotherapies in this and other areas, settings. British Medical Journal, 313, 402. since interactions may occur. For example, with -, Marsden, J., Stewart, D., et al (1997) The National Treatment Outcome Research Study in the United patients already stabilised on methadone mainten• Kingdom: Six-month follow-up outcomes. Psychology of ance, the commencement ofantitubercular therapy Addictive Behaviors, 11, 324-337. with rifampicin (Raistricket ai, 1996), or HIV treat• Hammersley, R, Lavelle, T. & Forsyth, A. (1990) Buprenor• phine and temazepam abuse. British Journal of Addiction, ment with zidovudine, can alter the breakdown of 85, 301-302. methadone. Patientsonthe anti-eoagulant phenytoin Hawks, D., Mitcheson, M., Ogbome, A., et al (1969) Abuse or rifampicin and some anti-HIV treatments may of methylamphetamine. British Medical Journal, 2, 715-721. Hendra, T. J., Gerrish, S. P. & Forrest, A. R (1996) Fatal need higher doses of methadone. Other anti-HIV methadone overdose. British Medical Journal, 313, 481-482. treatments may lead to potentially dangerously high Kahn, A., Mumford, J. P., Rogers, G.A., et al (1997) Double• levels (certainly higher than anticipated) of either blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. Drug and Alcohol Dependence, the methadone or the antimicrobial drugtreatment, 44,57-61. as is also seen with isoniazid. Kleber, H. D., Riordan, C. E., Rounsaville, B., et al (1985) Clonidine in outpatient detoxification from methadone maintenance. Archives of General Psychiatry, 42, 391-394. Kosten, T. R & Kleber, H. D. (1984) Strategies to improve Conclusion compliance with narcotic antagonists. American Journal of Drug and Alcohol Abuse, 10, 249-266. Lader, M. & Morton, S. (1991) Benzodiazepine problems British Journal of Addiction, 86, 823-828. Newapplicationsofexisting drugs and the develop• Ling, W., Rawson, R. A. & Compton, M. A. (1994) Substitution pharmacotherapies for opioid addiction: from mentofnew products havetransformed thesubstance methadone to LAAM and buprenorphine. Journal of misuse field. Previously, the interest in drug treat• Psychoactive Drugs, 26, 119-28. mentwas restricted to a few areas where the clinician lobI, J. K & Carbone, L. D. (1992) Emergency management of cocaine intoxication. Counteracting the effects of today's wished to be assured about the competence and 'favorite drug'. Postgraduate Medicine, 91, 161-162, 165-166. safety of management. Today it has become clear Marlatt, G. A. & George, W. H. (1984) Relapse prevention: that, alongside cognitive-behavioural and social introduction and overview of the model. British Journal of Addiction, 79, 261-275. components of treatment and rehabilitation, the Marsch, L. A. (1998) The efficacy of methadone maintenance drug therapies of the future expand greatly the interventions in reducing illicit opiate use, HIVrisk behaviour armamentarium of the clinician. The challenge is to and criminality: a meta-analysis. Addiction, 93, 515-532. Mitcheson, M., Edwards, G., Hawks, D., et al (1976) Treat• harness the power of pharmacotherapies in care ment of methylamphetamine users during the 1968 epidemiC. plansappropriateto the needsofindividual patients. In Drugs and Drug Dependence (eds G. Edwards, M. A. H. Russell, D. Hawks, et al). Famborough: Saxon House. Pemeger, T. V., Giner, F., del Rio, M., et al (1998) Randomised trial of heroin maintenance programme for addicts who References fail in conventional drug treatments. British Medical Journal, 317, 13-18. Raistrick, D., Hay, A. & Wolff, K. (1996) Methadone Advisory Council on the Misuse of Drugs (1988) AIDS and maintenance and tuberculosis treatment. British Medical Drug Misuse Report: Part 1. London: HMSO. Journal, 313, 925-926. Bammer, G. (1993) Should the controlled provision of heroin Strang, J. (1990) Intermediate goals and the process of change. be a treatment option? Australian feasibility considerations. In AIDS and Drug Misuse: The Challengefor Policy and Practice Addiction, 88, 467-475. in the 1990s (eds J. Strang & G. Stimson), pp. 211-221. Beam, J., Gossop, M. & Strang, J. (1996) Randomised double• London: Routledge. blind comparison of lofexidine and methadone in the in• - (1992) Harm reduction for drug users: exploring the patient treatment of opiate withdrawal. Drug and Alcohol dimensions of harm, their measurement and strategies for Dependence, 43, 87-91. their reduction. AIDS and Public Policy Journal, 7, 145-152. Carnwath, T. & Hardman, J. (1998) Randomised double• -, Darke S., Hall, W., et al (1996a) Heroin overdose: the blind comparison of lofexidine and clonidine in the case for take-home naloxone. British Medical Journal, 312, outpatient treatment of opiate withdrawal. Drug and 1435-1436. Alcohol Dependence, 50, 251-254. -, Sheridan, J. & Barber, N. (1996b) Prescribing injectable Darke, S., Ross, J. & Hall, W. (19%) Overdose among heroin and oral methadone to opiate addicts: results from the users in Sydney, Australia: I. Prevalence and correlates of 1995 national postal survey of community pharmacies in non-fatal overdose. Addiction, 91, 405-411. England and Wales. British Medical Journal, 313, 270-272. ·\ 1"1 (1'1'/'/1, ('01. ), JI- -l ,)-l I\ delI t" ~tl'tll1g

-&- (1997a) Heroin prescribing in the British system of 3. Regarding substitution agonist therapies: the mid-1990s: data from the 1995 national survey of a reduction in risk of transmission of HIV is one community pharmacies in England and Wales. Drug and Alcohol Review, 16, 7-16. of the aimsofmethadonemaintenance treatment -&- (1997b) Prescribing amphetamines to drug misusers: b injectable methadone has been shown to be Data from the 1995 national survey of community pharm• acies in England and Wales. Addiction, 92, 833-838. more effective than oral methadone inreducing -, Marks, I., Dawe, 5., et al (1997a) Type of hospital setting illicit drug use and treatment outcome with heroin addicts. Results from a c substitute prescribing of benzopdiazepines is randomised trial. British Journal of Psychiatry, 171, 335-339. appropriate for patients who misuse benzo• -, Beam, J. & Gossop, M. (1997b) Opiate detoxification under anaesthesia. British Medical Journal, 315, 1249-1250. diazepines in an intermittent 'binge' pattern -, Finch, E., Hankinson, L., et al (1997c) Methadone d buprenorphine is a possible alternative to treatment for opiate addiction: benefits in the first month. Addiction Research,S, 71-76. methadone for maintenance treatment of -, Powis, B., Best, D., et al (1999) Preventing opiate opiatedependence, and may be advantageous overdose fatalities with take-home naloxone: pre-launch as it cannot be injected. study of possible impact and acceptability. Addiction, 94, 199-204. Vining, E., Kosten, T. R. & Kleber, H. D. (1988) Clinical utility 4. In maintenance ofabstinence: of rapid c1onidine-naltrexone detoxification for opioid a naltrexone is effective in preventing relapse to abusers. British Journal of Addiction, 83, 567-575. Ward, J., Darke,S., Hall, W., et al (1992) Methadone cocaine use maintenance and the human immunodeficiency virus: b naltrexone can be used to help patients to current issues in treatment and research. British Journal of maintain abstinence from heroin use Addiction, 87, 447-453. Weinbroum, A. A., F1aishon, R., Sorkine, P., et al (1997) A c psychological approaches such as relapse risk-benefit assessment of fIumazenil in the management prevention workcan help patients abstain from of benzodiazepine overdose. Drug Safety, 17, 181-96. some risk-taking behaviourevenifthey are not World Health Organization (1992) ICD-lO Classification of Mental and Behaviour Disorders: Clinical Descriptions and completely drug-free Diagnostic Guidelines. Geneva: WHO. d lofexidine is designed to help maintaining abstinence in patients who have completed opiate detoxification

Multiple choice questions 5. Regarding harm reduction/prevention of complications: a injecting drug users should be advised about 1. Inoverdose: facilities for exchanging used needles and a the appropriate treatment for methadone over• syringes for clean injecting equipment dose is a single dose of intravenous naloxone b hepatitis B vaccination is rarely appropriate b intramuscular naloxone can be given in opiate for injecting drug users as most have already overdose ifthe intravenous route is difficult to acquired immunity by the time they present access for treatment c flumazenil competitively blocks the action of c patients on methadone will need their dose benzodiazepines and can be used in the reassessed on commencing treatment with management ofbenzodiazepineoverdose rifampicin d the risk of accidental overdose is increased d patients on methadone will need their dose when a dug user resumes use following a reassessed on stopping a course of treatment period ofabstinence. with rifampicin.

2. In withdrawal: a benzodiazepine withdrawal is best managed by prescribing a reducing regime of a short• acting benzodiazepine MCQanswers b depressed mood and suicidal ideation are recognised features ofamphetamine withdrawal 1 2 3 4 5 c lofexidine is a synthetic opiate used for the a F a F a T a F a T management ofopiate withdrawal b T b T b F b T b F d management of opiate withdrawal using a c T c F c F c T c T reducing dose of methadone can be planned d T d T d F d F d T over a period as short as 10 days.