Instructor: Dominic P. Decker, MS, CPhT
Introduction An article headline in a recent issue of The New York Times read, Dr. Griffith Edwards, Addiction Specialist, Dies at 83. To see a similar newspaper story prior to the latter third of the 20th century would have been nearly unthinkable, as addiction is a relatively new field of scientific study. In fact, the article is an obituary for the man who is largely credited with establishing addiction medicine. His accomplishments included defining alcohol and drug dependence and treating substance abuse, among many others. Benedict Carey, the article's author, reports, Dr. Edwards reshaped thinking about heavy drinkers and their problems, about the psychology of drug use and its treatment, and about the policy implications for governments and health agencies seeking to reduce abuse. He continues, He was among the first doctors to perform careful studies of skid row drinkers and of talk therapies for addictive drinking - these at a time, in the 1960s, when habitual drunkenness was considered a moral failing and virtually the only treatment was to dry out. As Dr. Edwards discovered in the course of his work, treatment modalities of alcoholism and other chemical dependencies vary by individual. Today, cognitive behavioral therapy can be used in conjunction with pharmacological interventions with varying degrees of success. Pharmacological treatment will be the primary focus of this continuing education feature. The pharmacy technician plays a vital role in ensuring the safe and efficient distribution of prescription medications. With increased knowledge of those medications indicated for the treatment of addiction, the technician will be poised to assist the pharmacist in providing optimal care to patients with this condition. Scope While much has changed since the 1960s, substance abuse and dependence present an ongoing problem in the United States, affecting a growing number of people from all segments of society. According to research conducted over the last two decades and cited in Clinical Work with Substance-Abusing Clients, edited by Shulamith Lala Ashenberg Straussner, it is estimated that 11 million adults are dependent on alcohol, while an additional 7 million are addicted to it. Furthermore, 14 million adults admitted to using illicit drugs in the year 2000. Data indicate that 2.8 million of those individuals were drug dependent and 1.5 million were drug abusers. Additional studies provide more insight into the scope of this problem. In 2003, a total of 22 million people, or nearly 10% of the total population of the US, were substance abusing or dependent. Straussner writes, The abuse of alcohol and other drugs affects individuals, families, communities, and society as a whole. Substance abuse causes more deaths, illnesses, accidents, and disabilities than any other preventable health problem today. And, in equally distressing statistics, it is estimated that the federal drug control budget allocates only 18% of its resources toward treatment, while 60% goes to prosecution for drug-related crimes. Language The language of addiction, relapse, and recovery is often complex. It is for this reason that we start with definitions used by those working in the field of addiction medicine. The Diagnostic and Statistical Manual of Mental Disorders (DSM), published by the American Psychiatric Association and soon to be released in its fifth edition, defines mental disorders in the context of diagnostic criteria. Among these disorders are substance abuse and dependence. According to the current edition of the DSM, substance abuse is a maladaptive pattern of substance use leading to clinically significant impairment or distress. Straussner elaborates that one or more of the following will be experienced within a 12-month period: The continued use of psychoactive substances despite experiencing social, occupational, psychological or physical problems Inability to fulfill major role obligations at work, school or home Recurrent use in situations in which use is physically hazardous, such as driving while intoxicated Recurrent legal problems related to the use of a substance In contrast to abuse, substance dependence is defined as experiencing at least three of the following seven symptoms in a 12-month time frame: Tolerance, as defined by either a need for increased amounts of a substance to achieve a desired effect or diminished effect with use of the same quantity of substances Withdrawal, as characterized by specific withdrawal syndromes defined for each substance, or using a substance in order to relieve or avoid withdrawal symptoms Taking the substance in larger amounts or over a longer period than was intended A persistent desire or unsuccessful efforts to reduce or control use A great deal of time spent obtaining, using and recovering from substance abuse Important social, occupational or recreational activities are given up or reduced because of the substance use The substance continues to be used despite knowledge of resulting serious physical or psychological problems Just as substance abuse and dependence are categorized, so are stages of treatment and recovery. The DSM specifies that individuals who formerly abused substances can be identified as in remission after use has ceased for at least one month. The stages of remission include: early full remission (substance-free for 1-12 months), early partial remission (intermittent, but infrequent use of substance within the first 12 months of recovery), sustained full remission (substance-free for more than 12 months), and sustained partial remission (substance use resumes after 12 months free of symptoms). Many individuals who have previously been abusing or dependent on a substance will always identify themselves in a stage of remission, regardless of how long it has been since their last date of use. This pattern suggests that alcoholism and other chemical dependencies present as ongoing challenges, requiring social support systems to maintain sobriety. Assessment Assessment of chemical abuse and dependency requires that health care providers be informed about how it manifests in the lives of their patients. Screening tools have been developed to facilitate this assessment process, two of which will be discussed here. As part of a routine office visit, a patient will be asked about the use of drugs and alcohol. Providers must approach these potentially sensitive topics in a non-judgmental way, as a patient who withholds this information from his or her health care provider risks continuing destructive behavior. Straussner writes, The clinician needs to remember that once individuals start abusing substances such as alcohol, opiates or cocaine, they often become addicted to them. They cannot just stop using the drug or drugs through willpower alone. She continues, They should not be condemned or made to feel guilty for their dependence on a chemical any more than a client would be condemned for having an uncontrolled medical condition. The CAGE screening tool has been developed specifically to assess for alcoholism. It can be used in a variety of health care settings due to its simplicity. Each letter of the test name represents a question to be asked: C:Have you ever felt that you should Cut down on drinking? A: Have people Annoyed you by criticizing your drinking? G: Have you ever felt bad or Guilty about your drinking? E: Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a hangover?(Eye opener) As is indicated by the National Institute on Alcohol Abuse and Alcoholism, a division of the National Institutes of Health, The CAGE can identify alcohol problems over the lifetime. Two positive responses are considered a positive test and indicate further assessment is warranted. The Drug Abuse Screening Test, or DAST, was developed to parallel the Michigan Alcoholism Screening Test. It utilizes a 28-point questionnaire that asks about the use of prescription or over-the-counter medications in excess of the directions and the non-medical use of other drugs. Respondents are asked to think about the past 12 months, then respond yes or no to a variety of questions, including: Have you used drugs other than those required for medical reasons? Have you abused prescription drugs? Are you always able to stop using drugs when you want to? Do you ever feel bad about your drug abuse? Each yes response is scored as a 1, except for three items on the questionnaire, in which a no response is scored as a 1. Data collected from this assessment reveal that a score of 6 or higher indicates the strong possibility of substance abuse or dependence, while a score of 12 or higher is definitive and requires further assessment, intervention and treatment. Etiology The phenomenon of substance abuse and dependence in this country and worldwide raises several questions about the etiology of the disorder. Why do some people become addicted, while others do not? Are certain individuals more likely to become addicted to a substance because of their race, ethnicity, gender or socioeconomic status? Do genetics play a role in families with multigenerational substance abuse? Is there a connection between substance use and mental health disorders? Research has shown patterns and trends among those who use drugs and alcohol. Despite this, Straussner notes that data collected reveal no single etiological factor that accounts for why some people become dependent on a substance and others do not. We again turn to research conducted within the past two decades for insight into proposed disease models. Perhaps most notable among these studies is that addiction can result from biochemical, genetic, familial, psychological, environmental and sociocultural factors, either individually or in combination. Recent findings in the area of environmental and sociocultural factors suggest that more substance use today can be linked to the increasing availability of drugs, social acceptance and idealization of drug use and the prospect of selling drugs for financial gain. A 2001 study showed that young adults who used marijuana were more likely to try other, more harmful drugs. But, of course, these findings tell only part of the story. More research in this field is necessary. Treatment As discussed earlier, a number of addiction treatment modalities exist. With the above theories of addiction in mind, Straussner suggests that it may be best to view substance abuse as a multivariate syndrome, in which multiple patterns of dysfunctional substance abuse occur in various types of people with multiple prognoses requiring a variety of interventions. Among these interventions is pharmacological treatment. Table 1 includes a summary of seven medications currently used for the treatment of alcohol, opioid and nicotine addiction. Three of these medications, representing each category of addiction, will be discussed in further detail. Antabuse (disulfiram) oral tablets are indicated for the treatment of alcohol addiction. As an alcohol agonist, disulfiram inhibits the oxidation of acetaldehyde. Metabolism of alcohol in the absence of disulfiram would degrade this product. When disulfiram is administered and alcohol ingested, acetaldehyde builds up in the body, producing a number of unpleasant side effects. These can include nausea, vomiting, headache, dizziness, flushing, sweating, thirst and weakness. The reaction is proportional to the amount of alcohol ingested and the dose of disulfiram, but it is important to note that reactions with the above side effects can happen even with small amounts of alcohol and last from 30-60 minutes to several hours. While the medication does not reduce the rate of alcohol metabolism, it can remain active in the body for 1-2 weeks after the last dose. Because of the potential for severe reactions, patients and family members should be thoroughly counseled about the effects of the medication. The medication is not to be administered to a patient who is actively intoxicated. A patient should abstain from alcohol for a minimum of 12 hours prior to taking a dose of disulfiram. Disulfiram is available in 250mg and 500mg tablets. Initial dosing is 500mg once daily for two weeks, typically in the morning. For those who experience drowsiness or fatigue while on the medication, the dosing schedule can be adjusted to bedtime. After the initial dosing period, a maintenance dose of 250mg daily is recommended. In all cases, dosing should not exceed 500mg daily. Concomitant administration of disulfiram and phenytoin can result in severe side effects. The latter drug is used in the treatment of seizure disorders. Disulfiram may inhibit the metabolism of phenytoin and thus decrease its elimination rate, resulting in increased serum phenytoin levels. In patients on both medications, phenytoin levels will have to be carefully and routinely monitored by the prescriber. Disulfiram prescribing information states that the medication should be used until the patient's alcoholism has been deemed in remission and under control. Pharmacological treatment can take a number of months, or even years, and will likely be coupled with cognitive behavioral approaches. Dolophine hydrochloride (methadone) oral tablets are indicated for the treatment of opioid addiction. Specifically, the medication is used for the treatment of moderate-to-severe pain that is not responsive to non-narcotic analgesics, detoxification treatment of opioid addiction or maintenance treatment of opioid addiction. Opioids are defined as heroin or other morphine-like drugs, including Duragesic (fentanyl), OxyContin (oxycodone), Dilaudid (hydromorphone) and Opana (oxymorphone). Methadone, as a mu-agonist, is a synthetic opioid analgesic that mimics the effects of morphine. Treatment of opioid addiction with methadone is coupled with additional social and medical services, as will be further explored. The historical use of methadone is of particular interest because of ongoing controversy surrounding it today. Two decades after its development as a long-acting analgesic, methadone began to be used for opioid addiction in the 1960s. It was during this time that the first methadone maintenance treatment program was opened at Beth Israel Hospital in New York City. Evidence of methadone administration as a solution for the growing opiate abuse problem was established, and maintenance programs became publicly funded in 1967. It is estimated that 179,000 people receive methadone treatment in licensed facilities in this country today. In a chapter of Straussner's book entitled The Treatment of Opiate Addiction, authors Ellen Grace Friedman and Robin Wilson outline the therapeutic uses of methadone, including the three mentioned above, that is, the treatment of pain, detoxification and maintenance. They write, The most common use of methadone, however, is as a long-term treatment, referred to as methadone maintenance. In this model, patients remain in treatment indefinitely and receive ongoing counseling, medical assistance and vocational services. Tapering from methadone is voluntary and neither encouraged nor discouraged. As cited by the authors, advantages of methadone maintenance programs include: oral administration, eliminating use of needles; cost-effective treatment; regular clinic visits and frequent interactions with health care professionals; and drug-related crime reduction. Disadvantages include: methadone is addictive (like heroin and other morphine-like drugs); use of methadone in pregnancy results in children being born addicted and requiring detoxification; and not promoting drug abstinence. Methadone is a Schedule II controlled substance and available in 5mg and 10mg tablets. Distribution of methadone for the treatment of opioid addiction is limited to programs that have been certified by the Substance Abuse and Mental Health Services Administration, a division of the U.S. Department of Health and Human Services. In initiating methadone treatment, the health care professional will consider several factors to determine the correct dose of medication. These include the opioid the patient had been taking previously, the degree of opioid tolerance, and the age, general condition and medical status of the patient. A typical initial dose is 30mg/day, while maintenance doses range from 80 to 120mg/day. Side effects include lightheadedness, dizziness, sedation, nausea, vomiting and sweating. Methadone interacts with cytochrome P450 inducers, such as carbamazepine, phenytoin and phenobarbital, and may be less effective when administered with these drugs. It also interacts with cytochrome P450 inhibitors, such as ketoconazole and erythromycin, and may be more effective when concomitantly administered. Chantix (varenicline) oral tablets are indicated as an aid in smoking cessation. The medication is a nicotinic receptor partial agonist. As such, it selectively binds to neuronal nicotinic acetylcholine receptors, preventing nicotine from binding to these receptors itself. In greater detail, the prescribing information states, Varenicline blocks the ability of nicotine to activate 42 receptors and thus to stimulate the central nervous mesolimbic dopamine system, believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking. Smokers who use varenicline will experience decreased, and therefore less rewarding, effects of nicotine ingestion. Varenicline carries with it a warning about serious neuropsychiatric side effects. Post-marketing reports have indicated increased instances of depression, psychosis, paranoia and anxiety, among others, in those being treated with the medication. Reports also indicate the potential for suicidal ideation, suicide attempt and completed suicide. While mood depression may be a symptom of nicotine withdrawal, depression and suicidal ideation have rarely been reported in those undergoing a smoking cessation program without medication. As the prescribing information states, These events have occurred in patients with and without pre-existing psychiatric disease; some patients have experienced worsening of their psychiatric illnesses. All patients being treated with Chantix should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness. Those who experience any of these symptoms should stop taking varenicline and contact their health care provider. The medication is available in 0.5mg and 1mg tablets. In the first week of use, it is dosed at 0.5mg once daily on days 1-3 and 0.5mg twice daily on days 4-7. In continuing weeks, dosing is 1mg twice daily for a total of 12 weeks. To increase the likelihood of sustained abstinence, the patient may repeat the 1mg twice daily dosing for an additional 12 weeks. Varenicline should be started one week before the date to stop smoking. Or, the medication can be started and smoking stopped between days 8-35. It should be taken after eating with a full glass of water after eating. Side effects of treatment with varenicline include nausea, vomiting, constipation and abnormal dreams. While no meaningful pharmacokinetic drug interactions have been recorded, the concomitant use of varenicline with nicotine replacement therapy products (e.g. gum, lozenges and patches) has been shown to increase the incidence of nausea, vomiting, headache, dizziness, and fatigue among other symptoms. Conclusion As noted earlier, substance abuse and dependence is a multivariate syndrome, that is, its etiology, symptoms and treatment vary according to the individual. With this in mind, health care providers must be responsive to the unique needs of each patient with this condition. The provision of care should be approached in a non-judgmental way. For many, addiction is out of the scope of their control. Social and medical treatment programs have been developed in response to this reality. The one type of treatment presented - pharmacological intervention - has proven to be successful when the patient has additional social supports. Thorough patient counseling is necessary for medications that have been developed for the treatment of addictive disorders, including the three discussed here. With knowledge of these medications, pharmacy technicians can identify patients in need of counseling and direct them to the pharmacist, thus ensuring the safe and efficient distribution of prescription medications. References Antabuse Prescribing Information (2012). http://www.drugs.com/pro/antabuse.html. CAGE Screening Test. National Institute on Alcohol Abuse and Alcoholism. http://pubs.niaaa.nih.gov/publications/arh28-2/78-79.htm Carey, B. (2012, September 25). Dr. Griffith Edwards, Addiction Specialist, Dies at 83. The New York Times, p. A25. Chantix Prescribing Information (2011). http://labeling.pfizer.com/ShowLabeling.aspx?id=557. Dolophine Prescribing Information (2006). http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM142842.pdf. Drug Abuse Screening Test. http://www.drtepp.com/pdf/substance_abuse.pdf. Friedman, E.G. & Wilson, R. (2004). The treatment of opiate addiction. In S. Straussner (Ed.), Clinical work with substance-abusing clients(187-208). New York: Guilford Press. Potenza, M., Mehmet, S., Carroll, K., & Rounsaville, B. (2011). Neuroscience of behavioral and pharmacological treatments for addictions. Neuron, 64(4), 695-712. Straussner, S. L. A. (Ed.). (2004). Clinical work with substance-abusing clients (2nd ed.). New York: Guilford Press. Author Biography Dominic P. Decker is a first year medical student at the University of Minnesota in Minneapolis. He holds a Master of Science degree in Narrative Medicine from Columbia University. He has seven years of experience working as a certified pharmacy technician in community pharmacy settings and has authored numerous articles for Today's Technician with a special interest in the interstices between communication, pharmacy, and medical practice. Idea in Brief While much has changed since the 1960s, substance abuse and dependence present an ongoing problem in the United States, affecting a growing number of people from all segments of society. Treatment modalities of alcoholism and other chemical dependencies vary by individual. Today, cognitive behavioral therapy can be used in conjunction with pharmacological interventions with varying degrees of success. Pharmacological treatment of addictive disorders will be the primary focus of this continuing education feature. Idea in Practice The pharmacy technician plays a vital role in ensuring the safe and efficient distribution of prescription medications. With increased knowledge of those medications indicated for the treatment of addiction, the technician will be poised to assist the pharmacist in providing optimal care to patients with this condition.