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