Pharmacopsychosocial Treatment of Opioid Dependence Harm Reduction Palliation or Simply Good Medical Practice

Opioid alkaloids have been used medicinally for centuries as analgesics, for their antidiarrheal and antitussive properties, and as hypnotics. Opioids were initially derived from the poppy plant (Papaver somniferum) by the ancients of the Mediterranean Basin. Written records of the medicinal uses of opioids date to before the time of Hippocrates (460–377 BC). Paracelsus prescribed opium in a medicinal drink of wine and spices in the 16th century. Sir William Osler, the renowned Canadian physician of the late 1800’s remarked that opium was “God’s own Medicine”. Opioids are considered superb medications by modern physicians, who widely prescribed them still and for the most part without significant adverse consequences. Yet there is a “dark side” to opioids for those who develop dependence on these drugs (1). Opioids have significant dependence liability because of compelling biphasic central effects, behavioral activation at low doses and sedation at higher doses, accompanied by allostatic neuroadaptation of the CNS, leading to use of rapidly escalating doses. These dynamics may be amplified in persons having altered dopamine receptors in the limbic system, suggesting a possible genetic association (2). Dependent individuals may be unable to stop compulsive self-administration of opioids, in part because of these plastic changes in the brain akin to learning and memory that are highly resistant to modification. Synaptic alterations in neurons of the reward and limbic circuits may irreversibly modify emotions and responses to the environment, thereby permeating the behavioral repertoire of the addict. Accordingly, it may be impossible for most actively dependent individuals to live a fulfilling life simply because so much of their effort becomes devoted to activities necessary to obtain illicit opioids, use them, and recover from their use. Indeed, some individuals who have been dependent on opioids may never be able to return to a normal emotional life without intensive ongoing therapeutic support that allows the acquisition of new learning and more effective coping. The goal of the psychiatrist is to assist the opioid dependent patient to achieve recovery from an opioid-focused life, to help the individual to live a full and balanced life that is no longer fixated on drugs. Those who addictively use opioids often develop complications, less from opioid use per se than from a life outside the law, a direct consequence of their involvement with illicit drugs. The life and exceptional achievements of Dr. William Halsted, first chief of Surgery at Johns Hopkins Hospital, suggests that chronic opioid use may not necessarily be incompatible with a productive life. (Halsted turned to daily morphine use in a futile attempt to “cure” his cocaine dependence, contracted via self-administration of cocaine during research studies to develop a surgical anesthetic. Halstead had ready, unrestricted access to inexpensive, high-grade morphine, so he encountered few of the problems common to users of street narcotics.) However, as opioids are obtained from “the street” (via illegal means), as is the case for the majority of addicted individuals, drugs are often injected without using safe sterile techniques, in uncertain quantities, or with potentially toxic impurities present. Also, individuals frequently must engage in criminality or risky sexual practices to obtain access to drugs. Accordingly, the economic burden of opioid dependence is profound for society in terms of HIV and hepatitis C virus transmission, direct healthcare costs, and indirectly through criminal activity, absenteeism, and lost productivity. Opioids can be administered intravenously, subcutaneously, transdermally, orally, or by inhalation. Heretofore, it was believed that injection opioid use was most addictive and hazardous to users due to accidental overdose and infectious complications because it was associated with irresistible and compulsive drug use, with intense euphoric effects, and with a particularly severe withdrawal syndrome if the drug is discontinued. However, it is now recognized that discontinuing orally administered high potency prescription opioids (e.g. oxycodone) is equally challenging for a dependent individual (3). Through widespread availability, misinformation, and the surreptitious (“Trojan Horse-like”) nature of effects on behavior, oral opioid use may actually represent a greater public health concern than previously appreciated. Opioid dependence, due predominantly to oral not intravenous use, currently represents the fastest growing addiction problem in the United States (4), and internationally, there are an estimated 15.6?million illicit opioid users (5). Deaths from overdose of prescription analgesics have more than tripled in the past decade in the U. S. according to an analysis by the Center for Disease Control and Prevention, now rivaling those due to other illicit drugs and even motor vehicle accidents (4). These deaths can occur as individuals seek a greater degree of intoxication or attempt suicide because of hopelessness associated with co-occurring psychiatric disorders. In fact, the presence of psychiatric co-morbidities, either predisposing to, or as a consequence of out-of-control opioid use, is the rule rather than the exception in opioid dependent individuals. For this reason, many believe that prescription opioids have a particular affinity for the mentally ill who tend to selectively become dependent when prescribed these medications for pain (6). We now face the imperative of both preventing opioid dependence as well as effectively managing the disorder and its complications. Opioid dependence cannot be attributed to physician misprescribing alone, as access to these drugs through illicit means has become quite easy and prevalent. Therefore, an increasing emphasis on teaching physicians how to prescribe these medications safely must be combined in equal measure with strategies to identify and manage the clinical consequences of the widespread abuse of opioids. The focus in this editorial is helping those who are opioid dependent return to a productive and fulfilling life and reducing their very high risk of infectious and other complications as well as deaths due to overdose. Historically, treatment of opioid dependence consisted of assisting the individual to achieve total abstinence from drugs using religious, social and psychotherapeutic means of support. Of course, the implicit expectation was that motivational underpinnings of the addict’s life could be sufficiently restructured during treatment (often lasting one year or more if delivered in a therapeutic community) to allow other more adaptive ways of coping with the vicissitudes of life than by using opioids. It was hoped that relapse could subsequently be avoided by a voluntary “choice” to not use drugs, undergirded by mutual social support from peers also on the road to recovery. What has become evident is that opioid dependence is a chronic, relapsing, potentially fatal illness—of the same genre as diabetes or hypertension—and that continuous treatment and lifelong support may be necessary to prevent complicating morbidity and premature mortality (7). Physician Health Programs in the United States achieved a model of sustained recovery from opioid dependence, which may be replicable, but currently is not available to those without the considerable support from their profession as well as significant disciplinary consequences of failure (loss of one’s license to practice medicine). The model is complex, and utilizes motivational enhancement, comprehensive assessment and intensive treatment, oversight of care, complete abstinence from all substances of abuse, assertive linkage to recovery support groups, and sustained monitoring with higher level of intervention if necessitated by relapse (8). Some short-term success has also been reported by drug courts, which apply similar treatment principles to addicts facing incarceration (9). However, only a minority of opioid addicts successfully achieved extended abstinence over the long term using a psychosocial model of treatment alone (10). For most, opioid dependence was characterized by a deteriorating clinical course associated with significant morbidity and mortality during repeated relapses. A competing perspective held by some psychiatrists was opioid dependence as simply a manifestation of other underlying psychiatric issues rather than a disorder in its own right (the “self-medication” hypothesis) (11). As a corollary of this viewpoint the primary psychiatric disorder should be the focus of treatment, with the hope that if the “underlying disorder” were treated, the opioid dependence would spontaneously resolve. Finally, some societies have chosen to view opioid dependence in criminal, rather than medical terms—incarceration may stop opioid self-administration, but it is questionable whether such individuals often return to a healthful and balanced life (12). In the last half of the 20th century, a significant paradigm shift has occurred in conceptualizing opioid dependence as a bone fide medical disorder in its own right (7), not simply a bad habit or the voluntary choice to use the drug to relieve emotional or physical pain (13). An important focus of clinical investigation became elucidation of pathophysiologic brain changes that can contribute to development of opioid dependence (14) and prescribing the appropriate medication to help treat opioid dependence became feasible (15). The recognition that addiction is caused by fundamental changes in brain limbic and reward pathways has suggested to clinical scientists the potential to modify some of these neuroadaptations using the tools of molecular neuroscience and pharmacology (16). The major role for pharmacologic treatment of opioid dependence has traditionally been acute detoxification to relieve the withdrawal symptoms that accompany cessatio

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