Running head: PHARMACOLOGICAL INTERVENTIONS

Pharmacological Interventions for Addiction Alan Kovin, M.S., LASAC

The Challenge

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION From the 2009 National Survey on Drug Use and Health, we have gleaned the following generalized statistical data on substance use in the U.S. There were almost 23 million persons that were classified with a DSM-IV definition of some form of substance abuse or dependence. Of that total, over 18.5 million individuals were defined to have abused or be dependent on alcohol. A subset of that population, 3.2 million were found to abuse other substances as well.

Prescription pain med use jumped to 1.9 million individuals. According to the National Institute of Health and the Substance Abuse and Mental Health Services Administration (SAMHSA), the estimate of hard core opiate addicts, varies somewhere between 750,000 to 1 million. The balance, of opiate users is likely using prescription drugs, methadone and a variety of street opiates including heroin, demerol, morphine or methadone. Substance abuse treatment admissions reporting primary pain reliever abuse skyrocketed from 18,300 in 1998 (1.1 percent of all admissions) to approximately 105,680 (5.6 percent) in 2008. (TED 2010). The economic costs of alcoholism and substance abuse are enormous. When considering combined costs of alcoholism and substance abuse to our society in terms of loss of income and productivity, crime, health care costs, damages to families, costs from police and penal systems and collateral damage to society in general, it is easily several hundred billion dollars per year. The former US Secretary of HEW, Joseph Califano estimated in 2007, that the cost could be as much as $1 trillion dollars per year just in the U.S. Perhaps the greatest challenges we face as a nation in terms of addressing alcohol and substance abuse are to create intelligent, integrated interventions that emphasize treatment rather than incarceration and to face the reality of substance abuse as a medical and biopsychosocial problem. So far, our addressing of the problem of substance abuse has been woefully inadequate. Out of the 23 million classified substance or alcohol abusers identified in the survey, only 4.3 million of then received any kind

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION of treatment for their disorder. The individuals that did not receive treatment cited as reason(s) not to seek treatment, (1) lack of financial resources, (2) lack of a viable programs either by

locale or type, and (3) a perceived lack of need for such help. The absence of effective efforts in the areas of information, prevention and treatment are sadly showing, as evidenced by the societal costs and the attitudes and results of this survey. For the past few years there have been efforts from both governing and clinical authorities to address the hodge-podge assortment of treatment protocols that are commonplace in the market. A response by the treatment community has been the adoption of evidence based treatments (EBT) interventions which have proven their worth and effectiveness through trials and statistical evidence. Adherence to EBT standards are now commonplace to both private insurance and to state and local treatment resources. We have yet to determine if the new Health Care Act of 2010 will require insurance companies to cover both physical and mental disease such as substance abuse treatment. The Disease Model of Addiction and Medication Assisted Treatment Gold, Brady and many others report that substance abuse and addiction causes physiological changes to various neurobiological systems. Inaba states, that once a user of opiates graduates from experimentation to addiction, treatment becomes a physiological as well as psychological process. The National Institute on Drug Abuse (NIDA) states that, Addiction is a complex but treatable disease that affects brain function and behavior. Drugs of abuse alter the brain's structure and function, resulting in changes that persist long after drug use has ceased. As a natural response to this addiction model, Medication (or Medical) Assisted Treatment (MAT) has developed as a best practices treatment regimen for addiction diseases of

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION alcoholism and opiate addiction. By that definition, it becomes useful to compare MAT to the treatment of other chronic disorders such as diabetes or high blood pressure. To that end, a long

term strategy of treatment can be developed, along with behavioral interventions which can help to change lifestyle and sustain recovery. It has been shown that in every aspect for alcohol use disorder (AUD) or opiate dependence, MAT can provide substantial relieffrom detoxification to maintenance. Medications can make detoxification bearable, relieving symptoms of anxiety, nausea, aches and delirium tremens. They can reduce cravings for substances, and behaviorally impact the ingestion of drugs of choice. When cravings and symptoms have lessened, counseling and psychological interventions can start to take hold, promoting additional adherence to the protocol, promoting additional coping mechanisms and initiating behavioral change. SAMHSA has summarized the important benefits of MAT in regards to the treatment of AUD. These include increased periods of abstinence (which can help the individual cope with stress and urges), reducing the possibilities of full blown relapse, stabilizing the brain cells and physiology of the client, enhancing clearer thinking, self-esteem and motivation to change, and providing more potential for counseling and self-help. There are a variety of clinics, both private and public, which utilize different MAT protocols to treat either alcohol, opiate, cocaine or gambling addictions. Here we shall discuss some widely used medications used for alcohol and opiate addiction. Generally, a MAT protocol will be used to treat initial detoxification and withdrawal symptoms, ongoing cravings, and symptoms which accompany cravings, such as anxiety. In addition to the pharmacological aspect of treatment, behavioral counseling is generally offered either individually and/or in a group setting. NIDA, in their publication, Principles of Drug Addiction Treatment: A Research Based

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION Guide offers some important considerations that practitioners need to follow, when implementing MAT:

1. No single treatment is appropriate for everyone. Care must be taken to match the regimen

with the client, especially in regards to the medical and psychological condition of the client. Additional care must be given if the client has (a) co-existing disorder(s).
2. Treatment must deal with the multiple needs of the client. This should include attention

not only to the medical and psychological needs of the client, but should also address their vocational, social and spiritual needs. Throughout treatment, assessment must be timely and complete, and modified as necessary. External drug use must also be monitored. 3. If MAT is used, then counseling is an integrated part of the treatment. The most common therapies include some version of cognitive therapy, along with motivational enhancement therapy.
4. Treatment needs to be administered for an adequate period of time. Treatment for

substance abuse is a long term proposition. Three months is minimum. Treatment should last for a year or longer. Some clients stay on methadone indefinitely, although most other programs for cessation of alcohol and opiates can usually be terminated after a year or so. A Survey of Medications used in MAT TIP 49 from SAMHSA provides treatment professionals with a treatment protocol for Alcoholic Use Disorder (AUD). It can also be adjusted to address opiate addiction as well. The medications used in this protocol include acamprosate (Campral), disulfiram (Antabuse), oral naltrexone (ReVia), and extended-release injectable naltrexone (Vivitrol). Well also discuss

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION buprenorphine utilized for detoxification from opiates, ondansetron, a multiuse pharmaceutical

discovered useful for AUD, and methadone, the most widely used MAT used for the treatment of opiate dependency. Acamprosate (Campral) has been used in the U.S. since 2004, with previous successful history in Europe since 1989. Its primary use is to reduce cravings for alcohol, helping with the symptoms of withdrawal and mood and sleep disturbances. It is intended for those clients seeking complete abstinence from alcohol. Although its mechanism of action is still not understood, it is thought to modulate GABA and glutamate receptors. It is also utilized for clients undergoing opioid maintenance therapy. It is taken as two delayed-release tablets, twice daily. Care must be taken for those clients with compromised renal function Disulfiram (Antabuse) is an older medication, first used in the U.S in 1948. It makes use of physiological aversive conditioning, by altering the metabolism of alcohol in the liver. The result is a buildup of acetaldehyde when alcohol has been ingested. This creates a number of very unpleasant symptoms including nausea, vomiting, tachycardia, dizziness and flushing. Disulfiram has had a mixed history in the past due to lack of compliance. New data is indicating that compliance has increased. It is also being looked at as a treatment for cocaine abuse. Oral Naltrexone (ReVia) was initially approved for the treatment of opiate addiction in 1984. It is an opioid antagonist theorized to block the opioid/alcohol receptors which are responsible for both urge and craving development and the effects of alcohol intoxication. There is also the possibility that it acts to disrupt functioning of the pathways in the brain responsible for reward/reinforcement in curbing the cravings and urges of both alcohol and opiates. Injectable naltrexone (Vivitrol) was approved by the FDA in 2005 and offers increased compliance. It is injected into muscle monthly, and works through sustained time release.

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION Although the concentration of the drug in the blood is less than its oral counterpart, its side effects are less of an issue than the oral preparation. Ondansetron is a promising serotonin receptor antagonist used in addressing clients who have developed alcoholism in their earlier years (early-onset alcoholism). It has been theorized

that these individuals can benefit from selective serotonergic agents, rather than those individuals who develop alcoholism later in life. Stanford University researchers have also demonstrated its usefulness in addressing opioid withdrawal symptoms. Buprenorphine is in the class of drugs known as partial agonists. It is able to activate and bind to receptors, but to a lesser degree than full agonists such as heroin and morphine. Increasing the dosage of buprenorphine does increase its opioid-like effects until a certain dosage, known as the ceiling. When the ceiling dosage of buprenorphine is reached, it changes function and acts like an antagonist, blocking and not activating receptors. Buprenorphine is utilized for opioid maintenance, as an alternative to methadone, and for medically supervised withdrawal. As a result of its unique properties buprenorphine has a lower potential for abuse, less potential for dependence, withdrawal symptoms and discomfort. When it is being used in MAT, its receptors cannot be displaced by heroin, morphine, or other opioids, thus blocking their effects. Buprenorphine comes in two forms: Subutex, buprenorphine alone, and Suboxone, a combination of buprenorphine and naloxone, an opioid antagonist. Suboxone was created as a response to the abuse of pure buprenorphine, which has some potential of being abused. If one tries to inject Suboxone, the naloxone has the greater effect, potentially initiating withdrawal symptoms. Since buprenorphine is not absorbed readily from the gastrointestinal system, it is administered sublingually and is available as 2 or 8 mg tablets.

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION Methadone maintenance treatment (MMT) is the most widely administered MAT for opiate dependence. Within a MAT setting, during withdrawal and detoxification from street opioids, methadone (or buprenorphine) is substituted. Methadone, a synthetic opioid, occupies opiate receptor sites, thus eliminating and blocking the sedative and euphoric effects of street drugs. It relieves withdrawal symptoms, cravings and urges and with stable dosing, causes little if any euphoria normally found with heroin and other opiates. It metabolizes slowly and thus allows an individual to participate within normal limits in society. The activities of intravenous drug use are eliminated, and with them, criminal activities that might be necessary to obtain funds to purchase illegal drugs. The treatment is relatively simple to administrate. Usually, on a

daily basis, generally in the AM, the client visits the clinic for his/her daily dose of methadone. It is usually given in solution with fruit juice. In some instances, if it can be shown that the client is trustworthy, multiple doses can be provided, such as in the event of a vacation, or a travel hardship. Some clinics provide behavioral counseling in conjunction with the medication. Of utmost importance are the dosages provided and the length of treatment. Studies have shown that the effectiveness of methadone is dose related, with higher doses proving more effective in reducing and eliminating heroin use. The higher dose also helps to keep the client in treatment, thus reducing potential criminal activity. Although many clients stay on methadone significantly longer than on other MAT protocols, it is necessary that the client adapt to a lifestyle without street drugs. NIDA recommends a minimum of 12 months treatment; many clients are on methadone for periods of many years. Generally, many, (but not all) clinics encourage detoxification after 1 year. Many of those clients that do detox, later relapse, and start the cycle again. This demonstrates the serious medical aspect of addiction and the fact that individuals

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION often require several rounds of treatment, especially with behavioral interventions, if they are to succeed with sobriety. However, some methadone clients do maintain their habits indefinitely. Counseling and Motivational Interventions Targeted medications are a powerful tool in assisting an addicted individual to focus on other aspects of living other than obtaining and using substances. It has been recognized that in order to properly address the behaviors that are characteristic for substance dependence, there must be accompanying behavioral treatments and/or counseling. Current evidence based strategies recommended by SAMHSA (TIP47) include cognitive-behavioral therapy, motivational enhancement therapy/motivational interviewing, individual group counseling, selfhelp groups such as 12-step and SMART, and relapse prevention training. Cognitive-behavioral therapy addresses the individuals ability to cope with stress, urges and triggers. It can provide a

variety of behavioral tools and skills which can assist the individual in self-efficacy, the ability to deal with everyday challenges, and to recognize the consequences of their choices. Motivational interviewing is a client-centered technique, whereby an empathetic counselor demonstrates motivational discrepancies between the clients present state of mind and behavior and desired goals. Individual therapy, delivered by practitioners with a variety of theories can be successful. Self-Help groups such as AA have been around for over 75 years and are still adjuncts to most programs of treatment. Their success rates by themselves without MAT are questionable. Assisted Recovery Centers of America, a private treatment center in Phoenix, Arizona, specializes in alcohol, opiate and process addictions. They follow a protocol that is known as the Pennsylvania Model of Recovery, developed by University of Pennsylvania Medical School researcher, Dr. Joseph Volpicelli. This regimen utilizes evidence based treatments which include many of the fore-mentioned medications for MAT. They specifically use non-spiritual or non-

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION faith based counseling methods, emphasizing cognitive-behavioral approaches both in their individual and group approaches. SMART Recovery is utilized in their groups. SMART Recovery is based on the Rational Emotive Behavioral Therapy (REBT) of Albert Ellis. It has developed many tools that clients can utilize in their own recovery. SMART Recovery is

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considered a self-help regimen, and is structured as a non-profit, world-wide corporation. They offer facilitating training to both professionals, as well as to interested and motivated individuals. Their self-help groups are available both on-line as well as in-person. Where do we go from here? SAMHSA, NIDA and various other governmental organizations have been actively providing substance abuse and treatment information regarding best practices and evidence based treatment to clinicians and practitioners for several years. Despite continuing prejudices towards MAT by various uninformed groups of treatment professionals and the general populace, there is firm support by the government for using these protocols. There is statistical information that MAT is quite effective when used with counseling and other behavioral therapies. SAMHSA reports that presently, MMT costs around $13 per day and is considered a very cost effective option in addressing opiate addiction. However, if we are to start to see significant success on the real war against drugs, smart competent leadership and solutions will be required. There is a significant lack of organization, cooperation and cohesion among various government and non-governmental entities involved in providing information and in resources for substance abuse treatment. There are no dynamic sources of data; timely and relevant statistical data is hard to come by. DATOS and the N-SSAT reports seem to be outdated, nor do they provide the type of helpful, statistical evidence of outcomes necessary to convince an

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION ambivalent public to provide drugs to drug addicts. Standardization of intake, assessment, and

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treatment protocols are present and required in all of the private methadone maintenance clinics, but not necessarily in clinics offering protocols such as MAT for alcoholism. The Assisted Recovery Center of America utilizes protocols found in the SAMHSA Guide, Helping Patients who drink too much, a Clinicians Guide. The state of Arizona does have a reference guide for general assessments of behavioral disorders, The Instruction Guide for the Assessment, Service Plan and Annual Update and Instruction Guide for the Assessment; however, when this writer queried both Arizona Behavioral Health Services and Magellan, the states Regional Behavioral Authority, neither could find any published standards on their website. What is apparent to this researcher is that we are looking at the wrong enemy. There needs to be a redirection of monetary resources and an inventory of strategies that are working, including MAT. If it is true, that substance abuse and alcoholism are costing the collective upwards to a trillion dollars each year, a reasonable investment is obviously prudent. Perhaps our leaders will consider the future quality of life to be as important as the futile investments currently being made in Afghanistan, and act accordingly.

PHARMACOLOGICAL INTERVENTIONS FOR ADDICTION References Arizona Department of Health Services, Division of Behavioral Health Services (2011) Provider Manual. Retrieved from: http://www.azdhs.gov/bhs/provider/sec3_9.pdf

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Carey, B. (2008) The Evidence Gap Drug Rehabilitation or Revolving Door? New York Times Department of Health and Human Services. Center for Disease Control. (2002) Methadone Maintenance Treatment. Retrieved from: http://www.cdc.gov/idu/facts/Methadone.htm Gold, P.B, Brady, K.T. (2003) Evidence-Based Treatments for Substance Use Disorders. Focus 1:115-122 American Psychiatric Association Gorski, T (2003) Best Practice Principles In The Treatment Of Substance Use Disorders Retrieved from: www.tgorski.com Inaba, D.S., Cohen, W (2007). Uppers Downers All Arounders (6th ed.). Medford, Oregon: CNS Publications, Inc. National Institute on Alcohol Abuse and Alcoholism. (2005 updated). Helping Patients who Drink too Much: A Clinicians Guide. Retrieved from http://pubs.niaaa.nih.gov/publications/Practitioner/CliniciansGuide2005/guide.pdf National Institute on Drug Abuse (NIDA). (rev.2009) Principles of drug addiction treatment: A research-based guide (2nd Edition Retrieved from: http://www.nida.nih.gov/podat/podatindex.html National Survey of Substance Abuse Treatment Services. (2008) The N-SSATS Report Retrieved from: http://www.oas.samhsa.gov/2k10/222/222USOTP2k10.htm SMART Recovery. General Information. Retrieved from: http://smartrecovery.org/

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Substance Abuse and Mental Health Services Administration (SAMHSA). (2009) Incorporating Alcohol Pharmacotherapies Into Medical Practice Retrieved from: www.kap.samhsa.gov/products/manuals/tips/pdf/TIP49.pdf Substance Abuse and Mental Health Services Administration (SAMHSA). (2005) Quick Guide For Physicians Based on TIP 40 Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Retrieved from: http://kap.samhsa.gov/products/tools/cl-guides/pdfs/QGP_40.pdf Substance Abuse and Mental Health Services Administration (SAMHSA). (2010). Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings. Retrieved from: http://www.oas.samhsa.gov Substance Abuse and Mental Health Services Administration (SAMHSA). (2006) TIP 47: Substance Abuse: Clinical Issues in Intensive Outpatient Treatment Retrieved from: http://www.kap.samhsa.gov/products/tools/cl-guides/pdfs/qgc_47.pdf Substance Abuse and Mental Health Services Administration (SAMHSA). (2010). Treatment Episode Data Set (TED) Report Retrieved from: www.oas.samhsa.gov/2k10/230b/230bPainRelvr2k10Web.pdf Vacovsky, Lloyd. (2011) Assisted Recovery Center, Phoenix, AZ. Interview