Description of the condition
The misuse of pharmaceutical drugs has been described as a major health problem. An estimated 26 to 36 million people were using opioids in 2010, with around half using pharmaceutical opioids (UNODC 2012). There are an estimated 15.6 million opioid-dependent people worldwide, with the global consumption of opioids considered to be increasing (WHO 2009). Opioid dependence is a chronic relapsing condition with significant cost to human life (Hser 2001; Grella 2011).
Dependence upon pharmaceutical opioids has been well established as a problem in the United States of America (USA) and Canada (Fischer 2012; Manchikanti 2012). In the USA, pharmaceutical opioids are reported to be increasingly used by young people, and pain medications are second to marijuana as the drug used by new illicit drug initiates (NSDUH 2011).
Globally, illicit opioid use is a major cause of mortality from both acute effects of intoxication (e.g. overdose and traffic accidents) and transmission of blood-borne disease associated with injection drug use (such as human immunodeficiency virus (HIV) and hepatitis C) Degenhardt 2009. In the USA, where pharmaceutical opioid use has been described as an epidemic, pharmaceutical opioid overdose is one of the leading cause of mortality, with deaths from pharmaceutical opioids exceeding the number of deaths from heroin and cocaine (Paulozzi 2006). In the USA in 2007, more people died from prescription opioid overdose than motor vehicle accidents and suicides (Manchikanti 2012). Similarly high rates of pharmaceutical opioid use have been described in Canada (Fischer 2012). Although other countries are yet to reach the magnitude of the problems seen in the USA and Canada, there is evidence of increased pharmaceutical opioid use and harms. A global review identified that pharmaceutical opioid diversion, non-medical use and injection was a considerable problem in the USA, South Asia, South East Asia and some European countries (Degenhardt 2007). In Europe, non-medical use of prescription opioids is documented, including the problematic use of non-prescription codeine in the United Kingdom (UK) and France. An estimated 1.6% to 1.7 % of the German population are thought to be dependent on prescription drugs (Casati 2012). Increasing treatment presentations with prescription and over-the-counter codeine opioids are reported in South Africa (Myers 2003), where five to eight per cent of treatment presentations are now associated with over-the-counter opioid dependence (Weich 2008). Increasing reports of use and harms with pharmaceutical opioids are also reported in Australia, with increasing mortality due to oxycodone, and increasing hospital presentations for pharmaceutical opioids including over-the-counter codeine (Frei 2010; Rintoul 2010; Roxburgh 2011). The number of hospital poisonings in Australia from pharmaceutical opioids exceeded heroin in 2004 and has continued to grow every year, and the number of treatment episodes for oxycodone doubled over a five-year period, though it still only represent a fraction of the treatment episodes for heroin dependence (Roxburgh 2011).
Description of the intervention
Opioid agonist treatments are established to be effective in the treatment of heroin dependence (Clark 2002; Faggiano 2003; Mattick 2009; Mattick 2014). The two main opioid agonist treatments that are widely available are methadone and buprenorphine.
Methadone is well established as a treatment and has a strong evidence base demonstrating its effectiveness in reducing mortality and substance use, improving physical and mental health outcomes, reducing criminal activity, and reducing HIV risk and risk behaviours (Caplehorn 1996; Amato 2005; Gowing 2011; Mattick 2014). Methadone is a synthetic μ-opioid agonist, and an N-methyl-D-aspartate (NMDA) antagonist. It has a half-life of 24 to 36 hours and has close to 100% oral bioavailability. Methadone is generally given as a single daily dose in the treatment of opioid dependence. Methadone doses of 60 to 100 mg have been demonstrated to be more effective in retaining people in treatment compared with lower doses (Faggiano 2003).
Buprenorphine is a partial opioid agonist, having a lower intrinsic activity at the opioid receptor, but due to its high affinity for the opioid receptor, being able to act as an antagonist blocking the effect of other opioids. Buprenorphine has a favourable safety profile due to its ceiling on respiratory effects (Walsh 1994), with mortality in treatment appearing to be relatively less common with buprenorphine compared with methadone in naturalistic study designs in Australia and France (Auriacombe 2001; Degenhardt 2009). Buprenorphine has poor oral bioavailability, and is available in sublingual formulations for the treatment of opioid dependence. Due to its pharmacological properties, buprenorphine is able to be given as larger doses every second or third day (Amass 2000).
Levo-alpha-acetylmethadol (LAAM) was concluded to be more effective than methadone for reducing heroin use (Clark 2002), but it is currently not commercially available. Other therapies such as slow release oral morphine have also been explored.
How the intervention might work
Opioid agonist treatment, also known as opioid substitution treatment involves prescribing maintenance dose of an opioid medication in place of the drug of dependence. Most of the original research done into opioid substitution treatment involved prescribing a legal opioid such as methadone or buprenorphine in place of an illicit opioid such as heroin. The provision of a regular dose of a legal and medically sanctioned opioid treatment enables a reduction in illicit or unsanctioned opioids use, with associated improvement health and social stability. The dose of the substitution medication is adjusted to a level that prevents withdrawal without causing sedation. Regular dosing maintains a fairly constant blood level, so that the sense of euphoria or intoxication usually associated with each dose of the drug (either illicit or prescribed) is lessened. Substitution treatment decreases the frequency and intensity of the cycle of intoxication and withdrawal, allowing the client to better address the associated issues necessary for recovery. Psychosocial support provided in conjunction with medication addresses the psychological health and social environment of the opioid user and helps to improve both the quality and duration of life (WHO 2009).
Opioid agonist treatment works by provision of a regular dose of μ opioid agonist that bind at the μ opioid receptor, alleviating opioid withdrawal symptoms. Providing a stable dose of opioid agonist has been demonstrated to lead to numerous health and social benefits for opioid dependent people, specifically though reducing illicit opioid use (Amato 2005; Mattick 2009; Mattick 2014), HIV risk behaviour (Gowing 2011), HIV seroconversion (MacArthur 2012) and criminality (Amato 2005; Mattick 2009). It has been proven to improve physical and mental health, and social functioning (Padaiga 2007; Mattick 2009; Mattick 2014) and reduce mortality (Degenhardt 2011).
Why it is important to do this review
Opioid agonist treatment is commonly initiated as a first-line treatment for individuals with pharmaceutical opioid dependence, even though much of the evidence base for the use of pharmacotherapy treatments in opioid dependence has been derived from studies conducted with primarily or exclusively heroin-dependent samples. Users of pharmaceutical opioids (i.e. both prescription opioids and over-the-counter opioids such as codeine) have been described in the literature to be a different patient population with a number of characteristics that differ from heroin-using populations, including having a higher prevalence of physical and mental health co-morbidities.
Prescription opioid dependence has been described to be at epidemic levels in the USA and has been reported to be increasing globally. Establishing an evidence base for treatment of prescription opioid dependence is therefore timely and critical. An emerging evidence base exists for the use of opioid agonist treatments in prescription opioid dependence, but a systematic review is yet to be conducted to determine whether similar outcomes can be expected for this new population of opioid dependent people. This review will fill an evidence gap informing clinicians about effective approaches using agonist pharmacotherapies for pharmaceutical opioid dependence.