Addiction: A Practical Guide Stuart Gitlow MD MPH MBA President American Society of Addiction Medicine
What is a Disease Is a disease simply a departure from normal biologic function? Normal curve with the departure being defined as a certain number of standard deviations from the mean - Mental retardation - Short stature - Depression
What is a Disease Is disease present if morbidity and/or mortality are impacted? Elevated blood pressure Elevated cholesterol Elevated serum glucose
What is a Disease disease /dis ease/ (dĭ-zēz ) any deviation from or interruption of the normal structure or function of any body part, organ, or system that is manifested by a characteristic set of symptoms and signs and whose etiology, pathology, and prognosis may be known or unknown. But what if we have a manifestation without any known distinct deviation from normal structure or function? Is the manifestation alone sufficient for the definition?
What is a Disease disease /dis ease/ (dĭ-zēz ) any deviation from or interruption of the normal structure or function of any body part, organ, or system that is manifested by a characteristic set of symptoms and signs and whose etiology, pathology, and prognosis may be known or unknown. But what if we have a manifestation without any known distinct deviation from normal structure or function? Is the manifestation alone sufficient for the definition?
Disease - Diabetes Initially, a behavioral syndrome Later discovery, a metabolic syndrome Still later, an autoimmune syndrome Finally, a genetic abnormality causing predisposition combined with an environmental insult giving rise to phenotypic expression What is the disease entity? When is the disease present? Which part should be addressed through treatment?
What is included in the disease definition? That is, does an individual with a specific set of symptoms and related findings have one disease, two diseases or many diseases?
Case #1 A 20 year old college student uses marijuana daily and has done so for five years. She presents to her physician with a complaint of sleep difficulties. Diagnosed with a sleep disorder, she is prescribed a sedative-hypnotic. Five years later, on an elevated dose of sedative agents, and still using marijuana daily, she complains of growing anxiety that is causing some functional impairment. Does the patient have a Dual Disorder?
Addictive Disease Where is the disease? Is the disease defined by the use of substances or by certain behaviors such as gambling? Is the disease defined by the way in which the patient utilizes substances or by the manner in which he engages in certain activities Is the disease present if those behaviors stop? Was the disease present before those behaviors began?
Definition #1 - Alcoholism Alcoholism is a primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. Note the absence of any reference to quantity or frequency of use.
Definition #2 Dependence Tolerance Withdrawal Use more/over longer duration than intended Desire/unsuccessful effort cut down/control Time spent obtaining, using, or recovering Social/occupational/recreational reduction Continued use despite knowing of persistent physical/psychological problem Pick any three from this set, noting that quantity and frequency are absent here as well.
Definition #3 Alcoholism Readdressed Alcoholism is a disease characterized by the repetitive and compulsive ingestion of any sedative drug, ethanol being just one of these It is absolutely critical to appreciate that this definition does not in any way specify which sedative agent is used, the frequency of its use, or the amount ingested.
Definition #4 - Addiction Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors. Addiction also affects neurotransmission and interactions between cortical and hippocampal circuits and brain reward structures, such that the memory of previous exposures to rewards (such as food, sex, alcohol and other drugs) leads to a biological and behavioral response to external cues, in turn triggering craving and/or engagement in addictive behaviors.
Cause of Addiction Genetic factors account for about half of the likelihood that an individual will develop addiction. Environmental factors interact with the person s biology and affect the extent to which genetic factors exert their influence. Resiliencies the individual acquires (through parenting or later life experiences) can affect the extent to which genetic predispositions lead to the behavioral and other manifestations of addiction. Culture also plays a role in how addiction becomes actualized in persons with biological vulnerabilities to the development of addiction.
What the definition of addiction does not say: We ve talked about a disease of brain reward, motivation, memory, and related circuitry. We ve talked about genetic abnormalities. We ve talked about environmental factors. What we have not talked about is the drug use or behavior itself. That is simply a manifestation of the disease, not part of the disease itself.
Sedative Pharmacology
Human Physiology
Normal Curve rotation
Genetic Manifestations Stimulus Augmentation is premorbid to addictive illness. Is it a sign that the predisposition to the disease is present? This is one likely physiologic basis of addiction, representative of the phenotypic expression but perhaps demonstrating the genotype prior the expression itself.
Addiction Definition (continued) The new definition speaks to the importance of environmental factors impacting the extent to which genetic factors are demonstrated.
Sociologic Study Psychological differences between frequent drug users, experimenters, and abstainers could be traced to the earliest years of childhood and related to the quality of parenting received. The findings indicate that (a) problem drug use is a symptom, not a cause, of personal and social maladjustment, and (b) the meaning of drug use can be understood only in the context of an individual's personality structure and developmental history. It is suggested that current efforts at drug prevention are misguided to the extent that they focus on the symptom, rather than on the psychological syndrome underlying drug abuse.
Dr. Block continued: It would appear that the roots of substance abuse are discernible, and perhaps modifiable, in early childhood. Are these the roots of substance use disorders, or was Dr. Block observing the environmental and sociologic underpinnings necessary for phenotypic expression? Shedler J, Block J. Adolescent drug use and psychological health: a longitudinal inquiry. Am Psychologist 1990;45:612-630.
Case #2 A 12 year old student has grown up in a family where substance use is common. His older brother openly smokes marijuana and both parents are rarely seen without alcohol nearby. His father is distant emotionally and often inconsistent and irresponsible in terms of both household management and parental duties. He feels lonely, isolated, and unrecognized. He would like to fit in, or at least figure out a way to ameliorate his feelings, which he is unable to express or share.
ASAM Definition ASAM recognizes the genetic issues, which we ve discussed, and the environmental issues that we just spoke of. There are other contributing factors incorporated into the new definition:
Other Factors The repeated engagement in drug use or other addictive behaviors, causing neuroadaptation in motivational circuitry leading to impaired control over further drug use or engagement in addictive behaviors
Other Factors Cognitive and affective distortions, which impair perceptions and compromise the ability to deal with feelings, resulting in significant self-deception
Other Factors Disruption of healthy social supports and problems in interpersonal relationships which impact the development or impact of resiliencies
Other Factors Exposure to trauma or stressors that overwhelm an individual s coping abilities
Other Factors Distortion in meaning, purpose and values that guide attitudes, thinking and behavior Distortions in a person s connection with self, with others and with the transcendent (referred to as God by many, the Higher Power by 12-steps groups, or higher consciousness by others The presence of concurrent psychiatric disorders in persons who engage in substance use or other addictive behaviors.
Behavioral Manifestations Excessive use and/or engagement in addictive behaviors, at higher frequencies and/or quantities than the person intended, often associated with a persistent desire for and unsuccessful attempts at behavioral control Excessive time lost in substance use or recovering from the effects of substance use and/or engagement in addictive behaviors, with significant adverse impact on social and occupational functioning (e.g. the development of interpersonal relationship problems or the neglect of responsibilities at home, school or work)
Behavioral Manifestations Continued use and/or engagement in addictive behaviors, despite the presence of persistent or recurrent physical or psychological problems which may have been caused or exacerbated by substance use and/or related addictive behaviors A narrowing of the behavioral repertoire focusing on rewards that are part of addiction An apparent lack of ability and/or readiness to take consistent, ameliorative action despite recognition of problems.
Cognitive Changes Preoccupation with substance use; Altered evaluations of the relative benefits and detriments associated with drugs or rewarding behaviors; and The inaccurate belief that problems experienced in one s life are attributable to other causes rather than being a predictable consequence of addiction.
Emotional Changes Increased anxiety, dysphoria and emotional pain; Increased sensitivity to stressors associated with the recruitment of brain stress systems, such that things seem more stressful as a result; and Difficulty in identifying feelings, distinguishing between feelings and the bodily sensations of emotional arousal, and describing feelings to other people (sometimes referred to as alexithymia).
Definition Important Points Addictive Illness Substance Use Do not look at quantity or frequency measures as being relevant to treatment efficacy, as they are not relevant to the disease definition Lifelong illness once initiated, whenever that is. Reflect upon the literature with a close eye upon accuracy and relevance.
Critical issues in Literature Review Inclusion criteria Must actually study the correct disease. How the disease is identified is critical. Outcome measures Must measure symptoms of illness. Control Group Must be receiving gold standard treatment. Duration As with any lifelong illness with long-term morbidity/mortality, there is a 5 year standard.
The COMBINE Study Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence The COMBINE Study: A Randomized Controlled Trial Inclusion criteria required patients to drink more than 14 drinks (women) or 21 drinks (men) per week during a 30 day period within 90 days prior to evaluation. Further, subjects had to have at least 2 heavy drinking days during this period in which they had more than 4 drinks (women) or 5 drinks (men). JAMA 2006;295:2003-2017
The COMBINE Study The study therefore did not evaluate alcohol dependence, but only those with the disease who drank heavily. The inclusion criteria did not look at other sedative use, but only use of the one sedative explored, alcohol.
The COMBINE Study Outcome Criteria: Percent days abstinent from alcohol and time to first heavy drinking day. So if Subject A drinks every other day after the intervention, that s the same outcome as Subject B, who goes 2 weeks without drinking, then drinks every day for the next 2 weeks. Given that alcoholics who drink on 10% of days have far worse morbidity/mortality than those without addictive illness who drink daily, these outcome measures are both unrelated to the disease definition and fail to imply actual improvement in any important variable.
The COMBINE Study The subjects were randomized to receive medical management plus medication, behavioral intervention only, or a combination of all three. Behavioral intervention was provided by masters level therapists. Medical management was provided largely by nurses, some MD s, and one PA. This was limited to discussion of medication and was therefore not medical treatment. Where is the gold standard treatment group?
Gold Standard Treatment Where is the treatment that has been repetitively demonstrated as being the most efficacious for longterm treatment of addictive disease? If the goal of a study is to demonstrate the efficacy of a new intervention, must it not be compared to an intervention known to have the best treatment efficacy?
Gold Standard Treatment We know that 70% should be the obtainable comparator: Domino KB, Hornbein TF et al. Risk Factors for Relapse in Health Care Professionals With Substance Use Disorders. JAMA. 2005;293:1453-1460. Flynn CF, Sturges MS, Swarsen RJ, Kohn GM. Alcoholism and treatment in airline aviators: one company s results. Aviat Space Environ Med. 1993 Apr;64(4):31-8.
COMBINE Study Within the study, treatment lasted 16 weeks, then stopped. Subjects were evaluated over the course of 52 weeks.
Injectable Naltrexone Study Efficacy and Tolerability of Long-Acting Injectable Naltrexone for Alcohol Dependence A Randomized Controlled Trial Conclusion was that long-acting naltrexone can be of benefit in the treatment of alcohol dependence. JAMA 2005: 293; 1617-1625
Injectable Naltrexone Study Inclusion criteria required heavy drinking Outcome measure was the event rate of heavy drinking days Drug was compared to placebo but not to gold standard treatment Authors confused morbidity/mortality from heavy drinking with m/m from addictive illness, stating, Of the various measures of drinking behavior, heavy drinking shows the highest correlation with negative life consequences such as impaired driving, interpersonal problems, and injuries.
Why has research gone astray? Confusion with respect to substance USE and the differentiation from addictive disease. Public Health drivers Clinical Expertise Definition and terminology disagreements.
SBI (Screening & Brief Intervention) How to screen for addiction How to screen for substance use What are the differences? What are the next steps? When should UDS be obtained? When should other laboratory studies be obtained? When is brief intervention appropriate or useful?
Case #3 Your new patient tells you, I never have any problem with alcohol. I just limit myself to 2 drinks whenever I go out.
Case #4 You ve asked your patient, now one year in recovery, whether she attends AA meetings. She says, Yes. What is your next question?
Case #5 You ve asked your 16 year old patient about the parties he is attending. He openly tells you that he got drunk at the last party, something that he hadn t done before. While he tells you this, you are focused on the electronic record, checking off checkboxes and hitting the NEXT button. What did you miss by not looking at him as he was telling you about the party?
Which is correct? Your patient is a 25 year old opioid addict whom you treat with buprenorphine. She provides a urine specimen which demonstrates the presence of buprenorphine but the absence of marijuana which has always been present before. She had not revealed to you her cessation of marijuana use. What do you say?
Which is correct? What do you say? 1) Congratulations I see you ve stopped using marijuana. 2) I know these urine specimens are obtained without observation. Is it possible you gave us someone else s urine? 3) There must have been a mistake. This isn t your specimen. Here s some water. Let s get another sample to test.
Medical Treatment? Medical treatment of any disease involves more than just biologic knowledge. We speak of the bio-psychosocial-spiritual approach to addiction treatment, but indeed that is representative of all medical treatment. It is the very definition of medical practice. Keeping the entire picture in mind will keep addiction treatment straightforward, with results coming in an expected and productive manner. You won t always be successful, and your patients won t always get better. But you will be, and they will, the vast majority of the time.