PreventionResearchQuarterly current evidence evaluated

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1 DRUG NFO clearinghouse PreventionResearchQuarterly current evidence evaluated December 2008 ISSN Pharmaceuticals

2 Prevention Research Quarterly: Current evidence evaluated ISSN DrugInfo Clearinghouse 2008 This publication is copyright, but its contents may be freely photocopied or transmitted, provided the authors are appropriately acknowledged. Copies of this publication must not be sold. The Issues Paper and the Reading and Resource List are part of the Druglnfo Clearinghouse s quarterly publications on drug prevention. Other publications and resources include the newsletter DrugInfo and a range of Fact Sheets tailored for specific audiences, such as professionals and others working in the drug prevention and related sectors, teachers, students, parents and others with an interest in drug prevention. The quarterly publications usually provide a range of perspectives on current research and best practice relating to a central theme in drug prevention. All these publications are available for download. The Druglnfo Clearinghouse provides a first port of call for workers, professionals and others seeking information on drugs and drug prevention. You can sign up for free membership at the DrugInfo website or by visiting, telephoning or writing to: Druglnfo Clearinghouse Australian Drug Foundation 409 King Street, West Melbourne, Victoria 3003 Australia Tel: (Victoria only) druginfo@adf.org.au Web: Any enquiries or comments on this publication should be directed to the Publishing Manager, Druglnfo Clearinghouse, at the above address. The research in this publication represents work done on behalf of the DrugInfo Clearinghouse by Suzanne Nielsen and Nicola Thompson. The work of the authors was supported by a Reference Group that included key stakeholders: Gwenda Cannard, Chief Executive Officer, Reconnexion Dr Malcolm Dobbin, Senior Medical Adviser, Drugs Policy and Services Branch, Department of Human Services Jenny Holmes, Senior Policy Officer, Mental Health and Drugs Policy, Department of Human Services Dr Martyn Lloyd-Jones, Specialist in Addiction Medicine, Department of Addiction Medicine, St Vincent s Hospital, Melbourne Rosemary McClean, Policy and Program Adviser, Australian Drug Foundation, Victoria Chantelle Miller, Senior Policy Officer, Drugs Policy and Services Branch, Department of Human Services Irvine Newton, Chairman, Harm Minimisation Committee, Pharmaceutical Society of Australia DrugInfo Clearinghouse is an initiative of the Australian Drug Foundation and the Victorian Government.

3 Issues Paper No. 7 December 2008 DRUG NFO clearinghouse Prevention of pharmaceutical drug misuse Suzanne Nielsen, Senior Research Fellow/Senior Pharmacist and Nicola Thompson, Research Fellow, Turning Point Alcohol and Drug Centre, Melbourne, Victoria The misuse of pharmaceuticals has gained increasing attention worldwide. Pharmaceutical opioids and benzodiazepines are two of the main drugs being misused and a range of harms have been reported in association with these pharmaceuticals. In addition, there is a hidden population who may experience problematic pharmaceutical use without coming to the attention of alcohol and other drug services. Some prevention initiatives have been identified for example, an effective multistage approach that resulted in a sustained reduction in benzodiazepine prescribing. Lower-level interventions were also identified to be effective at a population level. Prevention activities will need to take into account the different groups of people that use pharmaceuticals. While some prevention initiatives and treatments are already established, additional evaluation of current treatments and appropriate treatment services for pharmaceutical users is required. Introduction The misuse of pharmaceuticals has been described at epidemic levels in the United States of America (Compton & Volkow 2006; Lipman & Jackson 2006; Manchikanti 2006) and has increased significantly in Australia in recent years. This paper describes a range of prevention strategies that may be used to address these high levels of pharmaceutical misuse. The focus is on the misuse of pharmaceutical opioids (including over-the-counter codeine) and benzodiazepines. In addition to a review of relevant literature, key experts who have experience in a range of fields were consulted to inform this paper. For the purposes of this discussion the term misuse is used to describe any use of pharmaceutical drugs that is inconsistent with the intended use or directions. This definition incorporates a range of misuse including: Overuse, where a therapeutically prescribed drug is being used either at higher doses or for longer than intended. Dose escalation in some cases may be related to inadequate treatment of pain or anxiety, the development of tolerance or inadequate information relating to risks. Intentional misuse, where pharmaceutical drugs may be used, often in large doses and potentially intravenously, for the purpose of intoxication. This is often referred to as non-medical use. It should be noted that these two definitions may not be discrete categories but represent some examples along the continuum of pharmaceutical misuse. Indeed some people may transition along the trajectory from therapeutic use to overuse and ultimately to intentional misuse. So prevention strategies aimed at preventing overuse may also result in the prevention of some high risk intentional misuse patterns developing. Opioids and benzodiazepines are the most commonly misused pharmaceutical drugs. Opioids are commonly used to treat pain while benzodiazepines are used commonly for insomnia and anxiety. While most of the population use these pharmaceuticals as they are therapeutically intended, a small group will misuse these substances. Subgroups of problematic pharmaceutical users include those who unwittingly develop dependence due to inadequate information about the risks and those that may intentionally misuse pharmaceuticals as substitutes for illicit drugs. The 2007 National Drug Strategy Household Survey found that 2.5 per cent of the population reported non-medical use of pain killers or analgesics in the previous 12 months. One per cent reported nonmedical use of tranquillisers or sleeping pills (Australian Institute of Health and Welfare 2008). Morphine prescription per person among year olds in Australia has been reported to have almost doubled Issues Paper No. 7 December

4 from 1995 to 2003 (Degenhardt et al. 2006). Despite the range of harms caused by the misuse of pharmaceuticals, there appears to be a relatively low level of community and even professional concern around the misuse of these drugs, compared to illicit drugs such as heroin and methamphetamines (Drugs and Crime Prevention Committee 2007). There are some issues that are unique to pharmaceutical drug misuse. While pharmaceutical drugs can be misused, they are also prescribed for therapeutic purposes. Increasing restrictions on their use may have the unwanted effect of limiting their appropriate use to treat serious medical conditions. The tensions between preventing misuse and enabling therapeutic use must be carefully balanced. Opioids Opioids have a range of pharmacological effects including euphoria, analgesia (pain relief), sedation and respiratory depression (Gutstein & Akil 2006). Clinically opioids are used to treat pain, as cough suppressants and for substitution treatment for opioid dependence (Gutstein & Akil 2006; Mattick et al. 2008). The opioids most frequently used to treat pain in Australia include codeine, morphine and oxycodone. Methadone and buprenorphine are the main pharmacotherapies used to treat opioid dependence. Some over-the-counter (OTC) analgesics also contain the opioid codeine in combination with either paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen. While these products are also known to be misused, there is little data available on the levels of misuse of these drugs. These OTC pain relievers are intended for short-term use in the event of mild to moderate pain; however, there is evidence that some consumers are misusing them to the point where they suffer adverse side effects such as dependency (from codeine) and gastrointestinal complications from NSAIDs (Dutch 2008). Benzodiazepines Benzodiazepines are a class of pharmaceutical drugs commonly prescribed for insomnia, anxiety and panic attacks. The positive effects of benzodiazepines can include relaxation, calmness and relief from anxiety. However, even when used at therapeutic levels, benzodiazepines can cause a range of harms to the user including dependence, depressed mood and cognitive impairment (Ashton 2005). While short-term use of benzodiazepines may be appropriate for some conditions, such as anxiety and insomnia, non-drug treatments such as cognitive and behavioural therapies are first line treatments which deliver better long-term outcomes compared to benzodiazepine treatment (Australian Medicines Handbook 2008). It is important that benzodiazepines are not the only strategy used to treat these conditions. The increase in benzodiazepine and pharmaceutical opioid misuse has been attributed to their increased availability and the ease with which they can be obtained from doctors or trafficked on the street, as well as their affordability and consistency (Strategic Crime Analysis Unit 2002). Benzodiazepines, for instance, are among the most prescribed drugs in Australia. It is estimated that more than eight million prescriptions were issued in 2004 (Pharmaceutical Benefits Advisory Committee 2007). Misuse of pharmaceuticals Presentations relating to pharmaceutical misuse range from overuse to intentional misuse for euphoric effects. Experts have suggested that there are groups of pharmaceutical misusers that are not well understood. This hidden population includes those that develop dependence following medical use (known as iatrogenic dependence ). Included in this group may be those that have unwittingly developed dependence: using medication for pain, anxiety or insomnia for longer than intended and increasing doses as tolerance develops so that the drugs become less effective at the same dose. Another group using pharmaceuticals is people dependent on alcohol. In one Australian sample, people entering treatment for alcohol dependence also reported use of benzodiazepines (51%), antidepressants (47%) and other opiates (4%), although it is not possible to determine if use was non-prescribed (Holt et al. 2005). Yet another group is those with unmet mental health needs who may self-medicate with these substances (Harris & Edlund 2005). A recent review of 67 studies of abuse/dependence and aberrant behaviours in pain patients found overall the rate of dependence was very low (3.27%) among chronic pain patients, though reported rates in individual studies varied between 0 and 45 per cent. Development of dependence in this review was even lower (0.19%) in chronic pain patients that had no history of dependence/abuse. These findings suggest that rates of dependence to pharmaceuticals resulting 2 Prevention of pharmaceutical drug misuse

5 from the treatment of chronic pain may be lower than previously thought (Fishbain et al. 2008). The injection and other misuse of benzodiazepines and pharmaceutical opioids has been reported as common among injecting drug users (IDU; Australian Bureau of Criminal Intelligence 2002; Darke et al. 2002; Department of Human Services 2002; Black et al. 2008). Among people who inject drugs, the use of prescription opioids such as morphine appears to be inversely related to the availability of illicit opioids, with greatest use reported in jurisdictions such as the Northern Territory where illicit drugs are not commonly available (Black et al. 2008). Prescription drug misuse has also been noted as a concern in some rural areas in a recent parliamentary enquiry (Drugs and Crime Prevention Committee 2007). Illicit use and injection of buprenorphine became widespread following its introduction as a treatment for opioid dependence in 2001, although this varies significantly between Australian jurisdictions (Black et al. 2008). In Victoria, illicit buprenorphine use has been reported more frequently compared with other jurisdictions (Jenkinson et al. 2005); however, this may have changed with the uptake of the buprenorphinenaloxone combination product, which is intended to reduce intravenous misuse. Methadone injection has also been reported, with methadone being prone to diversion from medical treatment programs to the black market. Injection of both the syrup and tablet forms of the drug has been found to be widespread among IDU in many jurisdictions of Australia (Darke et al. 2002). Jurisdictions where unsupervised doses are less diluted have reported higher levels of injection (Lintzeris et al. 1999; Fiellin & Lintzeris 2003). Harms Harms relating to pharmaceutical misuse can occur from dependence, which may begin as a result of therapeutic use, or withdrawal. Health harms associated with injection of drugs intended for oral use include vascular damage, blood clots and increased risk of overdose. Other harms include crimes associated with diverting the drugs to the black market. Pharmaceutical opioids Repeated administration of opioids can result in physical dependence, which is associated with unpleasant physiological effects during opioid withdrawal. Drugs that have a shorter onset of action and half-life are generally associated with more severe withdrawal symptoms of shorter duration. Opioids with longer half-lives are generally associated with a more protracted withdrawal phase and milder opioid withdrawal symptoms. Long-acting formulations contain high doses of morphine or oxycodone designed for slow release over many hours. There is a substantial risk of overdose if these tablets are crushed. This results in immediate release of a potentially toxic dose of opioid. Therefore, consumers should be instructed to swallow tablets whole. Harms relating to OTC products that contain codeine have included stomach bleeds (Dutch 2008) and potentially fatal metabolic imbalances (Chetty et al. 2003; Dyer et al. 2004; Lambert & Close 2005). Anecdotal evidence suggests that in some cases, while patterns of high-dose use of OTC medication has occurred for some time, some individuals have not realised they were misusing pharmaceuticals until serious health harms occur. It is important to note that the risk of misuse must be balanced with the need to treat pain. While some dependence has been reported in patients with chronic pain, the rates of developing dependence where there is no history of substance dependence are very low (Fischer et al. 2008). Opiophobia, a fear of prescribing opioids, has the potential to be a problem, especially where it leads to suboptimal management of pain (Rupp & Delaney 2004). Benzodiazepines Benzodiazepines are extremely habit forming. Tolerance and dependence can occur within weeks, even at normal prescribed doses (Taylor et al. 2005; Denis et al. 2006). Iatrogenic dependence (dependence as the result of the prescription of benzodiazepines for legitimate purposes) is common. Individuals originally prescribed benzodiazepines for legitimate medical reasons may continue to seek these drugs in order to alleviate withdrawal symptoms, such as anxiety and insomnia. Paradoxically, these withdrawal symptoms are typically similar to, and can be confused with, the symptoms for which benzodiazepines were initially prescribed. Dependence is possible after only two to six weeks of continuous use and this is characterised by tolerance, withdrawal symptoms and compulsive use (Lingford- Hughes et al. 2004). Issues Paper No. 7 December

6 The symptoms of withdrawal from benzodiazepines can last from a few weeks to several months (Taylor et al. 2005). Commonly reported symptoms include insomnia, anxiety, depression, poor memory and concentration (Ashton 2005). The severity of withdrawal symptoms is associated with longer periods of use, use of high doses, the use of multiple benzodiazepines (Seivewright 1993; Ashton 2005), the use of short-acting potent benzodiazepines (Ashton 2005) and polydrug use (de Wet et al. 2004). Without strategies in place to manage the symptoms that the benzodiazepine was initially prescribed for (e.g. anxiety and insomnia), withdrawal from benzodiazepines is likely to be very difficult for the patient. Regular benzodiazepine use has been linked to cognitive impairment in the short and long term (Barker et al. 2004) and to higher rates of depression (Zitman & Couvee 2001). Harms from injecting pharmaceuticals People who intentionally misuse pharmaceuticals intravenously are at risk of considerable health harms. Benzodiazepine injectors have been found to have higher levels of polydrug use, high risk behaviours, and greater injection-related harms and mortality (Darke et al. 2002). Some of the consequences from injection of pharmaceuticals intended for oral or sublingual administration, such as buprenorphine and temazepam, have been reported in Australia (Breen et al. 2004; Aboltins et al. 2005) and internationally (Ruben & Morrison 1992; Del Giudice 2004; Loo et al. 2005). These include blood clots, amputation and serious soft tissue injuries (Feeney & Fairweather 2003). Respiratory complications have been reported from tablet ingredients accumulating in lung tissue (Lemoine & Dusmet 2000). High rates of adverse outcomes were specifically associated with the injection of temazepam gel-capsules before their removal from the market (Ruben & Morrison 1992; Mackenzie et al. 2000; Dobbin 2001; Aitken & Higgs 2002; Feeney & Gibbs 2002). Impact of pharmaceutical misuse on the health care system and broader community Harms from pharmaceuticals may extend beyond the user with impact on family, workplaces and the community as described in a recent parliamentary enquiry (Drugs and Crime Prevention Committee 2007). The acquisition of pharmaceutical drugs places significant burden on the health care system. One tactic employed to obtain prescription items is seeing multiple prescribers, often referred to as doctor shopping. This activity has been reported in the United Kingdom and Australia (Fountain et al. 1998; Kamien 2004). Benzodiazepine use has also been related to road vehicle accidents (Longo et al. 2001; Kelly et al. 2004) and implicated in a number of fatal accidents (Kelly et al. 2004). Low levels of organised crime have been linked with the misuse of pharmaceutical opioids and benzodiazepines in Australia (Fry et al. 2007). There may be some relationship between benzodiazepine use and criminal activity, with uncharacteristic behaviour including aggression and disinhibition related to benzodiazepine use (Australian Crime Commission 2003; Fry et al. 2007). Prevention strategies Despite a significant increase in the non-medical use of prescription drugs, the characteristics of some populations that misuse pharmaceuticals are not well described. There are a number of reasons for this. The person with problematic pharmaceutical use: 1. may not identify that they have an issue with non-medical use of pharmaceuticals they may perceive that because their medication is prescribed it is sanctioned by the prescriber and therefore not abuse 2. may not encounter the same legal problems as illicit drug users because their drug supply is generally able to be sourced legally 3. may perceive pharmaceuticals to be safer than illicit drugs, and are less concerned about their use 4. may not identify with or attend traditional alcohol and other drug services that were primarily developed to meet the needs of illicit opioid (heroin) users. As pharmaceuticals are generally supplied by a doctor and pharmacy there is a clear role for both prescribers and pharmacists to be involved in prevention initiatives. This is one key difference from illicit drug use: pharmaceutical misusers are generally already in regular contact with these health professionals. 4 Prevention of pharmaceutical drug misuse

7 Primary prevention: prevention of the uptake of drugs Primary prevention programs aim to reduce the likelihood of a person commencing drug use. They are not usually targeted to specific drugs but aimed more broadly at alcohol and illicit drugs. Primary prevention is a difficult concept to apply to prescription and OTC drug misuse because these drugs have a therapeutic use. Primary prevention for the misuse of these drugs potentially involves media campaigns, public education programs and more targeted approaches aimed at specific groups such as general practitioners (GPs), pharmacists and other health workers. As illustrated in the following case study, effective prevention strategies may need to use multiple interventions targeted at different groups to achieve a sustained effect on pharmaceutical use. There is a need for education of the community to improve awareness about the appropriate use of pharmaceuticals and risks of dependency. There is little evidence to support the effectiveness of media campaigns on their own in preventing the uptake or reducing the use of illicit drugs (Ritter 2007). Whether these strategies are effective in preventing prescription drug use is yet to be evaluated. Education of prescribers may be another important strategy in the area of pharmaceutical misuse. In fact a combination of education strategies for health professionals and consumers may be the most effective approach. Key experts consulted in the writing of this paper report that some prescriber education campaigns alone have been ineffective, suggesting that strategies relying solely on prescriber intervention may not be successful. An example of an intervention that involved prescribers, pharmacists and government was the initiative to reduce harms relating to injection of temazepam gel capsules in Australia (Dobbin 2002). This initiative involved a range of responses including scripted responses for doctors and pharmacists receiving requests for the gel capsule formulation and the direction to prescribe a tablet formulation that was not associated with the same harms. In 2004 the temazepam capsule formulation was withdrawn from the market; while benzodiazepine use remains high, the injection of temazepam in particular has reduced substantially (Black et al. 2008). Case study Multi-stage approach to benzodiazepine reduction (Dollman et al. 2005) A study conducted in a regional setting in South Australia used multiple approaches to reduce benzodiazepines use for insomnia. This study demonstrated that the use of multiple strategies (provision of guidelines, consumer information, media campaign and health professional training) could result in a sustained reduction in benzodiazepine use. This intervention looked at non-drug management of insomnia and resulted in a 19 per cent reduction in benzodiazepine prescribing. Features of the intervention included: consultation with consumers, prescribers, pharmacists, staff in residential aged care facilities and other health care workers an Insomnia Management Kit, including protocols and guidelines for use during consultations, designed to assist GPs and pharmacists discuss non-drug management of sleep problems education and training of GPs and community pharmacists on insomnia, the sleep cycle and the use of and withdrawal from benzodiazepines a media campaign focussed on raising awareness that GPs can help manage insomnia and that effective alternatives to benzodiazepines are available. This intervention resulted in a reduction in benzodiazepine prescribing that was not only sustained, but continued to decline after the period of the intervention. Prevention initiatives should take into account differences in populations (Boys et al. 2001). Research has found that a range of groups are susceptible to pharmaceutical misuse. So prevention initiatives that target these at-risk groups may be more effective than broad overarching campaigns. Guidelines Prescribing guidelines for benzodiazepines and opioids are generally aimed at GPs. The Royal Australian College of General Practitioners publishes Issues Paper No. 7 December

8 guidelines for benzodiazepines, which can be found at However, the uptake of these types of guidelines is considered to be inconsistent and could be improved, particularly in relation to issues such as preventing long-term benzodiazepine prescribing. In general terms, benzodiazepines are only recommended for short-term use and are often inappropriately prescribed for longer term use. The long-term use of benzodiazepines carries a risk of the patient developing dependence (Psychotropic Drug Guidelines Subcommittee 2003; Australian Medicines Handbook 2008). The National Strategy for Quality Use of Medicines describes a role for a number of key stakeholders such as health consumers, health professionals and the media in promoting quality use of medicine (Department of Health and Ageing 2004). Overall responsibilities for stakeholders are to: improve medication use by recognising when and where problems exist, identifying factors that contribute to those problems, initiating interventions to improve medication use and evaluating outcomes enhance understanding of the risk and benefits associated with the use of all medicines foster informed debate about the role of medicines in health care work in partnership to achieve quality use of medicines. In particular, the responsibility for health practitioners and educators to become more aware of the risks and benefits of medicines and the possibility of non-drug options may reduce the risk of pharmaceutical misuse. Monitoring systems Some systems exist that may help in the monitoring of pharmaceutical misuse, including: 1. A permit system for drugs of dependence Generally a medical practitioner must hold a permit: before treating a drug-dependent person with any Schedule 8 poison 1 before prescribing dexamphetamine, methylphenidate, buprenorphine or methadone (some exemptions may apply) to treat a person with any Schedule 8 poison for a period greater than eight weeks. 2. Pharmacists reporting Pharmacists are required to report cases where controlled drugs are being prescribed in quantities larger than appears reasonably necessary or are prescribed more frequently than appears to be reasonably necessary, or if prescription shopping is suspected. 3. The prescription shopping hotline The Prescription Shopping Information Service identifies patients who are getting Pharmaceutical Benefits Scheme (PBS) medicines in excess of medical need. Once registered, a doctor can find out if their patient has been identified through the program and find out information about PBS medications supplied to that patient. prescription-shopping 4. Retrospective prescription monitoring through the Pharmaceutical Benefits Scheme Records from government subsidised prescriptions can be used to monitor trends of supplies of medications with abuse potential or to detect excessive supplies to an individual. The prescription monitoring systems described above have some limitations, being largely retrospective. Information is often several weeks behind actual prescribing and does not include prescriptions that are not subsidised by the government. These monitoring systems can be used at a population level to detect pharmaceutical misuse, but may also be useful for individual clinicians (see Tertiary interventions on page 8). 6 Prevention of pharmaceutical drug misuse 1 Schedule 8 drugs are poisons to which the restrictions recommended for drugs of dependence by the 1980 Australian Royal Commission of Inquiry into Drugs should apply. These include morphine, pethidine, methadone, buprenorphine, codeine phosphate, oxycodone and flunitrazepam.

9 Real-time online prescribing information systems have been established overseas and have been recommended in a recent inquiry into pharmaceutical misuse in Australia (Drugs and Crime Prevention Committee 2007). Such monitoring systems allow prescribers and pharmacists to more easily detect problematic use of pharmaceuticals at the time of prescribing and dispensing. This type of realtime monitoring has been implemented in British Columbia, Canada (Chee & Schneberger 2003; British Columbia Government 2007), and is an effective strategy to detect and prevent pharmaceutical misuse (Wrobel 2003). It should be noted that these monitoring systems will not be effective for preventing misuse of OTC medicines such as codeine-based analgesics. Scheduling restrictions The Drugs and Crime Prevention Committee (DCPC) has recommended that consideration is given to rescheduling benzodiazepines (and specifically alprazolam) to Schedule 8 (Drugs and Crime Prevention Committee 2007). However, such suggestions are contentious due to the potential impact on good clinical practice and the risk of preventing effective treatment of some medical conditions. As a result, experts feel that effective strategies are more likely to involve pharmacist and prescriber education rather that regulatory restrictions on prescribing. Information for consumers Some other initiatives identified for prevention of pharmaceutical misuse include providing information about non-drug management of common conditions such as insomnia and anxiety. In Victoria, for example, the Better Health Channel has published fact sheets about managing insomnia and anxiety ( Nsf/pages/Sleep_problems_insomnia; www. betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/ pages/anxiety_disorders_overview). Some non-drug strategies that are promoted are not always found to be effective. When ineffective strategies are trialled and fail, it can be harder to convince consumers to try further non-drug strategies. This highlights the importance of ensuring information is evidence based. In addition, identifying the cause of symptoms such as insomnia is important in determining appropriate treatment. Patients may need to be educated that many of the non-drug approaches to insomnia and anxiety are long-term strategies that may involve treatment of underlying pathology. Such treatments take time and practice. Patients need to be educated that improvements may take weeks or months and that expecting to resolve anxiety or insomnia symptoms quickly is unrealistic. Secondary prevention: reduction of use and harm among users The aim of secondary prevention activities is to reduce harms associated with using drugs and the escalation of drug use. Secondary prevention strategies for pharmaceutical misuse may not be as well-developed as interventions for illicit drugs and strategies may vary among different cohorts of pharmaceutical users. There are few strategies in place for those who are at risk of iatrogenic dependence and this was identified by key experts as an area that needs to be addressed. Strategies for secondary prevention among benzodiazepine users may include education of prescribers about prescribing according to RACGP Guidelines: for short periods of time, smaller pack sizes or smaller quantities of benzodiazepines. The use of non-drug treatments to address psychological comorbidities such as anxiety and panic has also been identified as important. The current Australian Government Medicare initiative (the Better Access to Mental Health Care initiative) subsidises 6 12 sessions with a psychologist. This strategy enables non-drug treatments for a range of mental health disorders ( fact_sheet/). Treatment for benzodiazepine misuse is typically abstinence based, with research in the area focussing on abstinence as a main outcome (Denis et al. 2006; Oude Voshaar et al. 2006). Due to the short and long-term effects of benzodiazepine misuse, abstinence is the preferred outcome of most interventions. However, research shows that this goal may not be realistic. For many people, treatment does not result in abstinence (Miller 1992); even among mono-dependent benzodiazepine users, abstinence rates of around 25 per cent are usual after treatment (Vorma et al. 2003). Issues Paper No. 7 December

10 In light of such evidence, treatment interventions that aim to reduce benzodiazepine-related harm as well as use may be most practical. Currently there are limited resources available to service providers and users that address benzodiazepine-related harm reduction. Drug user groups in Australia have been at the forefront of providing benzodiazepine harm reduction information to injecting drug users. Peer-run education and information sharing workshops on overdose prevention have provided an opportunity to explore the overdose risks associated with combining benzodiazepines and opiates (Gore 1997; NSW Health Department 2000). There are few resources directed at opiate users that aim to educate users on the risk of overdose when combining opiates and benzodiazepines, such as the benzodiazepine fact sheet at There is also at least one resource available on how to decrease the possible harms associated with the injection of different benzodiazepine formulations (Australian Drug Foundation 2006). However, these peer interventions are yet to be formally evaluated. Additionally, while these information strategies may be effective where peer networks exist, anecdotal evidence suggests that many prescription drug users may not be in contact with peers in the same way that some heroin or amphetamine users are. This may limit the dissemination and effectiveness of these messages across a broader population of those who misuse pharmaceuticals. Additional research is required to better understand this hidden group of pharmaceutical users and to establish what interventions may be most effective to reach this group. The limited prevention strategies available for this group offer a clear opportunity to develop an evidence base in this area. Tertiary interventions Few interventions have been specifically evaluated in pharmaceutical misusers and some pharmaceutical users may not be attracted into traditional drug treatment services (Drugs and Crime Prevention Committee 2007). The failure to present for treatment for benzodiazepine dependence may be related to a number of factors including lack of established pharmacotherapies for benzodiazepine dependence, a lack of benzodiazepine-specific treatment services and the failure to recognise the need to treat benzodiazepine dependence. As prescription medications are obtained through a medical practitioner, they are often perceived as safe and those who are dependent may not recognise they have a problem and present for treatment (Drugs and Crime Prevention Committee 2007). Similarly, prescription opioid users may not attend for pharmacotherapies that have been researched and implemented primarily for heroin users. Treatments that are available to users of pharmaceuticals include: long-term residential rehabilitation short-term withdrawal (in-patient or home-based) longer term outpatient withdrawal counselling pharmacotherapy treatments (for opioid dependence). Current approaches to treatment Treatment for benzodiazepine dependence Population-based interventions have been found to be effective for general population treatment samples in the United Kingdom (Cormack et al. 1994; Morgan et al. 2002). Morgan et al. (2002) found that significant reduction in benzodiazepine use resulted from a low level intervention that consisted of a letter advising patients to reduce their benzodiazepine intake. Cormack et al. (1994) compared a letter-only approach to a letter plus information sheets and found both intervention groups significantly reduced their benzodiazepine use compared to the control; the added information sheets did not result in a greater effect. Both these studies suggest that simple interventions are important and cost effective. These low level interventions would be an ideal first step in addressing pharmaceutical misuse at a population level, with more tailored interventions requiring further evaluation and use for those who do not respond to low level interventions. Two meta-analyses have examined treatment for benzodiazepine mono-dependence (Denis et al. 2006; Oude Voshaar et al. 2006). These studies found transfer to a long-acting benzodiazepine and gradual tapering of dose to be effective. It should be noted that these studies excluded people with polydrug dependence, so treatment for benzodiazepine dependence in patients with multiple drug dependencies is yet to be evaluated. 8 Prevention of pharmaceutical drug misuse

11 Some studies looking at strategies for managing benzodiazepine misuse among methadone patients have suggested that prescribing a maintenance dose may be a potential treatment option for those unable to detoxify from benzodiazepines (Weizman et al. 2003). The cognitive effects of long-term benzodiazepine prescription require further evaluation (Barker et al. 2004). Due to the protracted nature of benzodiazepine withdrawal, longer episodes of treatment and a collaborative model of specialist and community services has been recommended (Thompson et al. 2008). Outpatient or home-based withdrawal episodes were recommended by key experts in preference to in-patient withdrawal and the Victorian State Government response to the DCPC report also highlighted that this was a preferred treatment approach (Victorian State Government 2008). The benzodiazepine-specific service Reconnexion is an example of a collaborative model for working with GPs to address benzodiazepine dependence. Treatment for pharmaceutical opioid dependence Few studies have focussed on treatments specifically for pharmaceutical opioid misusers; however, there is a strong evidence base for the use of methadone and buprenorphine in the treatment of opioid dependence (Mattick et al. 2008). Although these have not specifically been evaluated for treatment of dependence on pharmaceutical opioids, opioid substitution treatment was the main treatment of pharmaceutical opioid dependence identified by key experts. One barrier to treatment is that people who misuse pharmaceuticals may not present for treatment at a drug treatment service. These services are often identified as being for users of illicit drug only (Drugs and Crime Prevention Committee 2007). In the United States, where indicator data show pharmaceutical opioid dependence exceeds illicit drug use, the use of office-based buprenorphinenaloxone treatment has been proposed as an acceptable treatment option for this group (Sullivan & Fiellin 2008) and is currently being evaluated for this purpose. This approach could be applied in Australia; however, the restrictions around daily supervision of dosing at treatment initiation may be a disincentive for some to start treatment. It may be necessary to rethink the delivery of treatments for opioid dependence for different cohorts of pharmaceutical users rather than using a one size fits all approach. The comorbidity of chronic pain with prescription opioid dependence further complicates treatment and the need for additional pain management services has been identified as a key tertiary intervention strategy. Other tertiary interventions A range of strategies are recommended in the management of pharmaceutical misuse. These include interventions around the controlled delivery of medications and monitoring for additional pharmaceutical use. Pharmacy interventions including instalment dispensing Daily or instalment dispensing of pharmaceuticals at community pharmacies may assist in cases where dependence or difficulty managing medications is detected. In addition the recording of OTC codeine product sales may help in earlier detection of overuse. Any pharmacy-based interventions would need to be properly funded to enable them to address pharmaceutical misuse. A model for remuneration for pharmacists with instalment dispensing has been established in the United Kingdom and could be considered in Australia (National Health Service 2007). Screening Misuse of pharmaceuticals should be specifically asked about on entry into alcohol and other drug treatment. If drug use is asked about generically then use of pharmaceuticals may not be reported and subsequently addressed. As noted by a number of key experts, pharmaceutical misuse is thought to be under-reported, with a large hidden population. The issue of screening also relates to screening for underlying mental health comorbidity; if this is addressed, the need for pharmaceuticals such as benzodiazepines may be reduced. Monitoring for ongoing misuse of pharmaceuticals Clinicians should be aware of the monitoring systems (including limitations of monitoring systems) described above when providing treatment for patients who misuse pharmaceuticals. In addition to monitoring, contracts are recommended when prescribing pharmaceuticals for patients in a treatment capacity (Murray et al. 2002). Such contracts outline that patients should not seek pharmaceuticals from other sources, or give prescribed pharmaceuticals to others, as a part of the Issues Paper No. 7 December

12 treatment agreement. Objective measures (such as urinalysis) should be used in addition to self-report mechanisms to assess ongoing pharmaceutical use. Self-help or peer support groups There are few self-help options specifically for prescription opioid dependence and limited research evidence generally to support self-help groups for people who use drugs with the exception of Alcoholics Anonymous (AA). The development of self-help groups such as SMART recovery (www. smartrecoveryaustralia.com.au) may be of assistance to people with problematic pharmaceutical use. Evaluations of these groups are currently underway that may provide evidence of their effectiveness. Internet-based treatment such as online counselling may also be a suitable alternative for pharmaceutical users not wanting to enter traditional treatment services. New pharmacotherapies A range of pharmacological interventions have been trialled for the treatment of benzodiazepine withdrawal and a number of these were included in the reviews by Denis et al. (2006) and Oude Voshaar et al. (2006). While some medications show promise for future use, in all cases further research is recommended (Oude Voshaar et al. 2006) and none of these medications are currently approved for these purposes in Australia. Typically, pharmacological interventions seek to assist in aiding withdrawal and managing acute withdrawal symptoms. Both Denis et al. (2006) and Oude Voshaar et al. (2006) found evidence that the use of carbamazepine (an anticonvulsant and mood-stabilising drug) and imipramine as pharmacological interventions were potentially effective. Other suggested interventions requiring further research and randomised trials are the use of flumazenil (a benzodiazepine antagonist) and other antidepressants. As discussed previously, benzodiazepine maintenance is generally not supported by research although it occurs reasonably often in practice, particularly among Opiate Substitution Therapy (OST) service users (Weizman et al. 2003; Lingford-Hughes et al. 2004). Maintenance prescribing of benzodiazepines has been suggested for benzodiazepine-dependent methadone consumers with a long history of misuse and previous unsuccessful attempts at withdrawal (Seivewright 1993; Weizman et al. 2003). In such cases, a risk-benefit analysis may conclude that maintenance treatment with benzodiazepines is appropriate (Taylor et al. 2005). However, the potentially harmful cognitive effects of long-term maintenance benzodiazepine use in this group require further evaluation to inform prescribing practices. Conclusion Currently there is little known about the range of populations that misuse pharmaceuticals or what treatments may be effective. There are established treatments for opioid dependence and an evidence base for the management of benzodiazepine monodependence. Effective prevention strategies have been demonstrated to involve a range of interventions delivered together and targeting both the consumer and health professionals. Guidelines and principles around quality use of medications and prescribing pharmaceuticals may contribute to reducing pharmaceutical misuse. Acknowledgments Thanks to all of the key informants for their time and expertise: Rodger Brough, Director, Southwest Health Care Drug and Alcohol Services Gwenda Cannard, Director, Reconnexion Will Day, Consumer Ros Burnett, Clinical Nurse Consultant Irvine Newton, Community Pharmacist, Chair Harm Minimisation Committee, Pharmaceutical Society of Australia John Sherman, Open Family Mathew Frei, Addiction Medicine Physician, Southern and Eastern Health Malcolm Dobbin, Senior Medical Advisor, Drugs Policy and Services Branch, Department of Human Services Sarah Lord, Vivaids Alan Freedman, Pharmacy Guild of Victoria 10 Prevention of pharmaceutical drug misuse

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