Prescription Opioid Addiction:

Transcription

1 Vol.8 Issue 12 December Prescription Opioid Addiction: Treatment Challenges The Power and Responsibility in Health Care s Information Revolution New Fixed-dose Combination, New Epilepsy Drug and Alert FDA Watch New Fixed-dose Combination, New Epilepsy Drug, and an Alert Bringing health care into the comfortable setting of your home (413)

2 Prescription Opioid Addiction: Treatment Challenges By Madeleine Sheldon-Dante Fast Facts Hydrocodone was the single most prescribed drug in the United States in 2010, with million prescriptions written. The Growing Epidemic of Prescription Opioid Addiction Over the past few years, the abuse of prescription painkillers has rapidly become a serious threat to public health. A 2007 study found painkillers to be the fastest growing recreational drug, with 2.14 million new users that year. Prescription painkillers are the second most common initiation drug after marijuana; of the estimated 2.7 million teenagers and adults who experimented with illicit drugs for the first time in 2007, 19% of them did so with prescription painkillers, 1 leading many to call them the new gateway drug. This surge in popularity is due in part to a widespread and devastating misconception, especially among young people, that prescription painkillers are safe to abuse recreationally. Unfortunately, this perception could not be more misguided. In 2009, over 343,000 emergency department visits involved prescription painkillers, a figure more than twice that of 5 years prior. Accidental fatalities involving painkillers have increased fourfold since 1999, by 2007 outnumbering deaths from heroin and cocaine combined. 2 Many consumers do not realize that popular painkillers, such as Vicodin, codeine, hydrocodone, Oxycontin, and Percodan, are opioids that work just like heroin and have a similar pharmacology and addiction potential. For a patient taking opioids for pain or a teen experimenting with pills, celebrities in the news may be their only exposure to the drug rehabilitation process, and they may not appreciate just how dismal recovery rates are for painkiller addictions. According to Tod Miller, MD, Medical Director for Behavioral Health, The Windham Center, Springfield Medical Care Systems, Bellows Falls, VT, If one observes a group of problem drinkers who meet the criteria for alcohol addiction, almost 90% of them will manage to stop drinking, and many never need treatment. The statistics are almost exactly reversed with opiate addiction. Even with treatment, only 10% 20% of these patients ever get off opiates; most In 2007, 18.1% of recreational painkiller users acquired the drugs from their physician. Approximately 45.8% acquired the drugs from a friend or relative who acquired them from a physician. Accidental fatalities involving painkillers have increased fourfold since 1999, by 2007 outnumbering deaths from heroin and cocaine combined. Among substance users, the most common reason for failing to find treatment is a lack of health coverage and an inability to afford treatment costs. continue to use or die from their use. Geoffrey Kane, MD, Chief of Addiction Services, Brattleboro Retreat, Brattleboro, VT, likewise acknowledges recidivism, In spite of everyone s best efforts, relapse rates to opioid use are very high. Opioid Addiction Treatment Illicit opioids, as well as the opiate pain medications prescribed by physicians, resemble the opiates naturally 4 December 2011

3 Respondents Geoffrey Kane, MD, MPH Chief of Addiction Services Brattleboro Retreat Brattleboro, VT Tod Miller, MD Medical Director for Behavioral Health The Windham Center Springfield Medical Care Systems Bellows Falls, VT Patrice Muchowski, ScD Vice President of Clinical Services AdCare Hospital Worcester, MA produced in the body and bind to the same receptors that are activated by the body s three opioid hormone families, the endorphins, enkephalins, and the dynorphins. All opioids have an inhibitory effect on neurons, which accounts for the gradual decrease in global brain metabolism seen in opiate addicts. Intelligence and productivity plummet. Where the receptors are found on inhibitory neurons secreting gamma-aminobutyric acid, a releasing effect may be seen in the areas those neurons would otherwise inhibit. This probably accounts for the initial pleasurable effects early in the addiction process, a rush wistfully remembered by addicts and rarely experienced later. The locus ceruleus is the major source of noradrenalin in the brain and a principal player in drug dependence and withdrawal phenomena. Chronic inhibition by opioids causes these neurons to upregulate their excitability to maintain their level of activity at pre drug-dependent levels. Since these neurons are central to the body s response to danger and pain, restoration of their previous level of activity eliminates much of the reward experienced when first abusing these drugs. Now, any reduction in drug levels leaves these upregulated neurons unopposed and wildly firing so the addict experiences painful symptoms of withdrawal. Most of the drug dose taken is just to avoid that pain, and the brain will upregulate again to match All opioids have an inhibitory effect on neurons, which accounts for the gradual decrease in global brain metabolism seen in opiate addicts. Intelligence and productivity plummet. any increase over that dose. More and more drug is required just to avoid the pain of withdrawal. Getting high necessarily becomes a losers game. The treatments for prescription opioid addiction and heroin addiction are functionally identical. Patrice Muchowski, ScD, Vice President of Clinical Services, AdCare Hospital, Worcester, MA, explains, There is very little treatment difference between people addicted to heroin and people addicted to prescription opioids. The primary difference is the psychological mindset. Those addicted to painkillers might ask their physician to cut their prescription when they realize that they are dependent; people addicted to heroin almost never ask for a reduced dose. The struggle with opioids is the craving associated with the addiction. Kane adds, Practically, there is no distinction between prescription opioid addiction and heroin addiction. At least for short-acting opioids, the pharmacology is the same, and the withdrawal is the same. If people are tolerant to one short-acting opioid, such as heroin, they are generally tolerant to other short- 6 December 2011

4 acting opioids, such as oxycodone and hydrocodone. Approaches to therapy can be divided into two main categories: abstinence-based treatment and medication-assisted treatment. In abstinencebased treatment, the goal is for patients to be completely free of opioids and any other addictive substances, allowing their natural brain chemistry to slowly renormalize over time. In contrast, medication-assisted treatment includes the administration of a long-acting opioid to protect patients from symptoms of withdrawal, to reduce or prevent opioid craving, and to improve the patient s quality of life. The duration of treatment with long-acting opioids varies but can range from months to years to life-long use. Detoxification The first phase of abstinence-based addiction treatment is medically assisted detoxification (detox) from the opioid. Detox may take place in a hospital, outpatient clinic, primary care office, or even a prison. The goal of detoxification is to ease a patient through the worst stages of opioid withdrawal, keeping the individual safe and limiting discomfort. Detoxification is most commonly accomplished by stabilizing patients on a long-acting opioid, typically methadone or buprenorphine. The dose is then gradually tapered and discontinued over 6 8 days (when treated in a hospital setting) or as long a days (when treated as an outpatient). 3 Alternatively, patients can be detoxified with an adrenergic agonist, such as clonidine. It is postulated that this drug reduces withdrawal symptoms by inhibiting the locus ceruleus, an area of the brain that would normally be inhibited by opiate receptors in a healthy individual. 4 In one approach, a constant dose of clonidine is administered for 10 days and then rapidly tapered off over 3 days. A third, and more controversial method of detox is ultra-rapid withdrawal, using opioid antagonists, such as naltrexone, naloxone, or nalmefene. In this method of detoxification, a patient is dosed with naltrexone under heavy sedation or anesthesia. Naltrexone binds very strongly to opioid receptors but has none of the euphoric effects, effectively blocking receptors and causing almost instantaneous withdrawal. The entire procedure takes just 5 days, and patients report very little pain; 5 however, many in the medical community believe that insufficient evidence exists to support the procedure s efficacy and that the cost and potential health risks outweigh the benefits. Three recent studies showed patient completion rates between 72% and 90% for the opioid-tapering method, using buprenorphine, and between 11% and 50% for the adrenergic-agonist method, using clonidine. 6 8 Two other studies showed patient completion rates between 98% and 100% for the ultra-rapid naltrexone withdrawal method. 5 9 A review comparing methadone, buprenorphine, and clonidine detox found buprenorphine and methadone to be the most effective methods of opioid detoxification followed by clonidine. 10 Outpatient Follow-up After detoxification is complete, a second phase in abstinence-based addiction treatments sometimes include therapy with another form of medicine, one that will block the effects of opioids if the person were to use any. Without structured medical follow-up and the accountability that goes with it, many patients will relapse into drug use in the weeks and months following detox. As Muchowski explains, The recidivism rate for detox alone, whether done at Some physicians dispense too many pain relievers much too readily; when patients complain that they need more and their prescription is increased, many patients are likely to take the initial lower dose and divert the rest. home or as an inpatient, is poor. This is because these patients are physiologically still craving the drug. They feel miserable so it is just too easy for them to reach for something that will make them feel better. It is especially critical to prevent relapse at this point in treatment, because opioid tolerance decreases during detox, and the risk of a fatal overdose is high if recreational opioid use is resumed. Therapy also involves counseling and extensive use of interpersonal supports but may also include the use of a medication such as naltrexone. Naltrexone therapy typically consists of oral naltrexone, administered daily or three times a week. The naltrexone binds very strongly to opioid receptors in the brain, preventing recreational opioids from 8 December 2011

5 having any effect and making relapse physically impossible. Naltrexone is extremely effective when patients comply with treatment, but it is less popular among patients than other forms of treatment. Because naltrexone does not stimulate the reward pathway, many patients will stop taking it. A systematic review found naltrexone therapy to result in slightly better patient outcomes than a placebo group, with the exception of incarceration rates, which naltrexone significantly improved. 11 A newer, more promising pharmaceutical option is sustained-release naltrexone. Various implants and injectable preparations, such as Vivitrol, have been developed to release naltrexone over time periods ranging from 1 6 months. Sustained-release naltrexone has been shown to reduce opioid abuse significantly and to increase treatment retention when compared to oral naltrexone. 3 However, there is a serious risk of fatal overdose if a patient resumes illicit drug use. Medication-assisted Therapy An alternative to abstinence-based therapy, medication-assisted therapy is the best-known form of opioid addiction treatment in the United States. In medication-assisted therapy, an illicit opioid is replaced with a long-acting, legal opioid, most commonly methadone or buprenorphine. Medication-assisted therapy treats addiction as a chronic disease and focuses on improving patients quality of life, helping them participate more normally in society, reducing their criminal behavior and use of injection drugs, and lowering their risk of HIV and hepatitis C. The longer duration of action of these particular prescribed opioids means a steadier concentration in the brain, and patients no longer experience the harmful cycles of withdrawal and intoxication that result from addiction to short-acting illicit opioids. The legal opioid most commonly used in medication-assisted therapy is methadone. Methadone is a highly controlled substance, and special regulations exist when it is dispensed in the context of addiction treatment. By federal law, physicians in regular practice settings may only prescribe methadone for the treatment of pain. Methadone may be prescribed for the treatment of opioid dependence only within special, Drug Enforcement Administration registered methadone clinics. A daily oral dose of liquid methadone will suppress drug cravings and withdrawal for hours, while partially blocking the euphoric effects of heroin and other opioids, helping methadone to discourage relapse. Several reviews have found that methadone maintenance treatment reduces illicit drug use and increases patient retention in treatment. Studies also show some decrease in injection drug related infections (i.e., HIV) as well as a possible increase in the patient s quality of life. 3 Another opioid widely used in medication-assisted therapy is buprenorphine. Buprenorphine is only a partial opioid agonist, and as a result, its effects reach a ceiling where they no longer increase with dose. This makes buprenorphine less effective in treating patients with heavy opioid habits but also makes buprenorphine less likely to produce intoxication or overdose than methadone. It is partially due to this ceiling effect that physicians are legally allowed to prescribe buprenorphine for addiction treatment in a primary care setting. Buprenorphine does have the potential to be injected recreationally, which is why the preferred delivery method is a tablet or a strip of film called Suboxone that contains both buprenorphine and the opioid antagonist naloxone. When the tablet is properly administered under the tongue, the naloxone is poorly absorbed and the buprenorphine behaves normally. If someone tries to misuse the Prescription opioids are definitely being overprescribed. It is important to figure out how to manage chronic pain without opioids, because that is where the prescription abuse begins. medication, by dissolving or injecting it, then the naloxone can throw an opioiddependent person into withdrawal, discouraging further misuse of the medication. Research suggests that, in medium-to-high doses, buprenorphine reduces illicit opioid use better than a placebo, but not so in low doses. 12 Studies also indicate that Suboxone may be as effective as methadone with regard to the retention and prevention of illicit opioid use. 3 Controversy Surrounding Methadone Clinics Though research has verified the effectiveness of methadone maintenance treatment, much heated controversy still surrounds methadone clinics. Some view methadone maintenance programs as legalized drug dealing, a 10 December 2011

6 replacement of one addiction for another. Methadone clinics have developed a reputation for intoxicated, loitering patients and diversion of take-home doses, 13 and some patients continue to use illicit drugs in addition to their daily methadone. Many young people addicted to prescription opioids need primary rehabilitation. They need to learn how to live normally, how to go to school or work, and how to develop meaningful relationships; all of these skills have been hijacked by their addiction. However, many in the medical community see this as a problem with clinic management, not with methadone maintenance as a methodology. 13 Muchowski argues, There are good treatment facilities and bad treatment facilities. Methodone definitely has a place in opioid addiction treatment. The respondents were unanimous in their support of methadone maintenance as a treatment option. Kane explains, Much of the public s resistance to methadone programs is based on unfortunate stereotypes. Some methadone patients continue to use drugs and some continue to deal drugs, but many others do extremely well. Miller, points out, When addicts take methadone, they do not automatically become angels, but the average criminal activity drops to 30 days a year from 330 days a year, and they are less likely to engage in behavior that would allow them to contract HIV or hepatitis C. So from a public health perspective, this is the treatment of choice. The root of clinic mismanagement may be the shift from public clinics towards privately owned, for-profit clinics. For-profit clinics have no financial motivation to taper patients off methadone. Anecdotally, a psychiatrist friend lamented, I have had patients ask me to help them reduce their methadone doses, because the methadone clinic was not helping them to do this. Comprehensive Patient Treatment The one thing that all the above treatments have in common, whether abstinence-based or medication-assisted therapy, is that they are only effective when supported by counseling and lifestyle changes. Miller explains, Many young people addicted to prescription opioids need primary rehabilitation. They need to learn how to live normally, how to go to school or work, and how to develop meaningful relationships; all of these skills have been hijacked by their addiction. Patients recovery can be jeopardized by friends who abuse drugs, and cravings can be triggered merely by being in a location where opioids were once used. Kane explains, Patients seeking recovery from addiction need to keep their distance from the people, places, and things associated with their substance use. They also need to cultivate positive relationships that will help them to grow personally and become more integrated, capable individuals who are less susceptible to using any addictive substances. Patients must rebuild their support structures by reconciling with friends and family, seeing therapists, and joining peer support groups. Medical and legal problems should be addressed. They should cultivate hobbies and explore ways to have fun while sober; for this purpose, voucher programs exist to provide recovering patients with discounted entertainment. Improving Prescription Opioid Addiction Treatment The growing crisis of prescription opioid addiction is an overwhelming problem, but there are simple measures that can be taken to combat it. First, obstacles to adequate treatment must be removed. An extensive national survey found the number one reason addicts seeking help failed to receive treatment was a lack of health coverage and an inability to afford treatment costs. 1 Things are considerably better in Massachusetts where health care coverage is government mandated. Muchowski explains, There are many more treatment resources in Massachusetts than in other states; mandatory insurance coverage has resulted in an increase in the number of patients who are getting treatment for addiction. Second, painkillers must be prescribed more conservatively. In 2010, hydrocodone was the single most prescribed drug in America, with million prescriptions written that year. 14 The majority of painkillers that are ending up on the streets are not coming from dealers but from legitimate prescriptions from physicians. A 2007 survey found that 18.1% of recreational painkiller users acquired the drugs from 12 December 2011

7 their physician, and 45.8% acquired the drugs from a friend or relative who acquired them from a physician. Just 4.1% purchased them from a drug dealer or other stranger. 1 One inner-city pharmacy intern confided, About 100 people come to our pharmacy each day, and at least 50% come in with prescriptions for painkillers. One customer pulled out a box cutter in an attempt to stab the security guard after it was found that she had a fake prescription. Some have attributed overprescription to advocacy work by non-profit groups such as The American Pain Foundation, which invented the concept of pain as the fifth vital sign, 15 and which quietly If we can keep kids from using substances into their twenties, the likelihood of them developing problems is much reduced. gets the majority of its funding from the pharmaceutical company that produces Percocet. 16 Muchowski argues, Prescription opioids are definitely being overprescribed. It is important to figure out how to manage chronic pain without opioids, because that is where the prescription abuse begins. Miller agrees, Some physicians dispense too many pain relievers much too readily; when patients complain that they need more and their prescription is increased, many patients are likely to take the initial lower dose and divert the rest. Finally, the most important tool to combat prescription opioid addiction is education. With such discouraging relapse rates for opioid treatments, the only way to reduce addiction in the United States may be prevention. The public must be made aware of the considerable risks of prescription painkillers and the extremely low rates of addiction recovery. Muchowski concludes, If we can keep kids from using substances into their twenties, the likelihood of them developing problems is much reduced. It seems to be related to the fact that the adolescent brain is still developing so when opioids are put into that brain, normal development is disrupted. Whatever can be done to prevent the experimentation of adolescents, the better off they will be later in life. References 1. Substance Abuse and Mental Health Services Administration. (2008). Results from the 2007 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NSDUH Series H-34, DHHS Publication No. SMA ). Rockville, MD. 2. Prescription Drugs: Abuse and Addiction (October 2011) National Institutes of Health NIDA Research Report Series. 3. Lobmaier P, Gossop M, Waal H, et al. The pharmacological treatment of opioid addiction a clinical perspective. Eur J Clin Pharmacol. 66: , Devenyi P, Mitwalli A, Graham W. Clonidine therapy for narcotic withdrawal. 127(10): , Beaini AY, Johnson TS, Langstaff P, et al. A compressed opiate detoxification regime with naltrexone maintenance: patient tolerance, risk assessment and abstinence rates. Addict Biol. 5(4):451 62, Ponizovsky AM, Grinshpoon A, Margolis A, et al.. Well-being, psychosocial factors, and side-effects among heroin-dependent inpatients after detoxification using buprenorphine versus clonidine. Addict Behav. 11: , 2006 (Epub 2006 Mar 9). 7. Marsch LA, Bickel WK, et al. Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial. Arch Gen Psychiatry. 62: , Ling W, Amass L, Shoptaw S. A multi-center randomised trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network. Addiction. 100: , 2005 [SD-008]. 9. Krabbe PFM, et al. Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: abstinence rates and withdrawal distress experiences. Addiction Biol. 8: , Meader N. A comparison of methadone, buprenorphine and alpha2 adrenergic agonists for opioid detoxification: a mixed treatment comparison meta-analysis. Drug Alcohol Depend. 108(1 2): , Kirchmayer U, Davoli M, Verster AD, et al. A systematic review on the efficacy of naltrexone maintenance treatment in opioid dependence. Department of Epidemiology, ASL RM/E, Rome, Italy. 12. Mattick RP, Kimber J, Breen C, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev Batki S, Kauffman J, Marion I, et al. TIP 43 Medication-assisted Treatment for Opioid Addiction in Opioid Treatment Programs, Treatment Improvement Protocol (TIP) Series 43, Chapter The IMS Institute for Healthcare Informatics The Use of Medicines in the United States: Review of 2010 April imshealth.com/deployedfiles/imshealth/ Global/Content/IMS%20Institute/Static%20 File/IHII_UseOfMed_report.pdf. 15. Reeves J. An Interview with James N. Campbell, MD, APS President, American Pain Society Bulletin. 17(1), Annual Report, American Pain Foundation publications/files/2010-annual-report.pdf. 14 December 2011