REVIEW QUESTIONS ANSWER KEY (CHAPTERS 1–13)

CHAPTER 1

• 1

  B. Male gender, younger, low SES, single

  Young unmarried men of low SES carry the highest risk for developing alcohol use disorder (AUD). Generally speaking, most present with early symptoms of AUD before the age of 30. Other risk factors include having a family history of AUD, having comorbid depressive disorders, schizophrenia spectrum disorder or personality disorders and a personal history of abuse.

• 2

  E. Dimension 6

  The ASAM PPC are the most commonly used standardized criteria used to attribute the appropriate level of care for patients taking into consideration their various clinical needs (dimensions). The six dimensions evaluated in the PPC are:

  • Dimension 1: intoxication and withdrawal potential

  • Dimension 2: biomedical conditions and complications

  • Dimension 3: emotional, behavioral, or cognitive complications

  • Dimension 4: readiness to change (transtheoretical model of change or stages of change)

  • Dimension 5: relapse or continued use potential

  • Dimension 6: recovery environment (including social, legal, vocational, educational, financial, housing factors)

• Dimension 6 addresses the patient's recovery environment, including barriers for their sobriety and support system. Services addressing Dimension 6 include ensuring one's ability to attend their clinical appointments (transportation, ability to take a medical leave), reside in a safe environment conducive to recovery (such as a sober house) and home cohesiveness (family members attending Al-Anon).

• 1

  D. Women with SUDs experience significantly more severe adverse medical and psychological consequences than men.

  Telescoping refers to the phenomenon whereby SUD severity progresses faster for women than for men, with women more likely to seek SUD treatment and be in recovery faster than men. Women with SUD appear to be more vulnerable than men to experiencing adverse consequences of using substances.

• 2

  D. Treating co-occurring psychiatric disorders leads to improved SUD outcomes.

  As noted above, the telescoping phenomenon posits that women are more likely to seek SUD treatment and be in recovery faster than men. Overall, recovery rates are equivalent between women and men. SUD treatment programs that offer comprehensive psychiatric care for women with SUD, including treatment for co-occurring psychiatric pathology, as well as addressing any abuse history, family dysfunction are associated with better outcomes. Gender-specific treatment settings have not been shown to be associated with any improved treatment outcomes.

• 3

  A. Naltrexone

  There is still no FDA-approved pharmacotherapeutic treatment of gambling disorder. Studies have suggested the involvement of the μ-opioid system in the reward processes of behavioral addictions leading to the hypothesis that opioid antagonists can reduce the repetitive behaviors and the urges of addictive behaviors such as gambling. Controlled studies on naltrexone, an opioid antagonist, have shown positive results in reducing the desire to gamble. There has not been a significant difference between bupropion or mood stabilizers such as lithium, topiramate, and placebo to treat gambling disorder.

• 4

  C. Telescoping Phenomenon

  Sex differences have been noticed in gambling behaviors. It has been found that females have a progression from nonproblematic to excessive engagement in gambling behaviors later in life than males. It also progresses faster from recreational to problematic. This phenomenon is described as the telescoping effect or phenomenon.

CHAPTER 2

• 1

  D. Acamprosate

  The U.S. Food and Drug Administration (FDA) approved three medications to treat AUD: disulfiram, naltrexone and acamprosate. Of these, acamprosate would be the preferred medication to use in patients with hepatic insufficiency. It is excreted in urine as an unmetabolized drug. As a result, it should not be used as a first-line agent for patients with renal impairment. Naltrexone is metabolized hepatically via noncytochrome-mediated dehydrogenase and is subject to the extensive first-pass effect. Its use can be associated with increased serum transaminases, and it is contraindicated in patients with acute hepatitis or hepatic failure. Disulfiram is metabolized hepatically via glucuronidation. Its side effects include cholestatic hepatitis, fulminant hepatitis, and hepatic failure. It is relatively contraindicated in patients with hepatic cirrhosis. Gabapentin and ondansetron are used as second-line treatment options for AUD but are not FDA approved for this condition.

• 2

  C. He should be screened for depression on admission and reassessed frequently thereafter

  It is not uncommon for patients with SUDs to present with various co-occurring psychiatric symptoms, particularly mood and neurovegetative symptoms. It is important to assess any such symptoms seriously on an ongoing basis to determine whether the patient requires active treatments, including medications and specialized psychotherapies, and to prevent serious complications of untreated psychiatric illnesses, including profound functional decline and/or suicidal behaviors. Many patients with substance-induced mood disorders would be expected to improve after being abstinent for a few weeks. Others might suffer from independent or secondary psychiatric disorders.

• 3

  C. Alcohol withdrawal

  This patient presents with a history of anxiety symptoms and panic attacks that occurs mostly in the mornings, after abstaining from any alcohol use overnight. Consuming alcohol leads to a resolution of his symptoms. This is consistent with alcohol withdrawal–related panic attacks and anxiety. Panic attacks related to substance use are seen most commonly with marijuana and LSD intoxication and alcohol withdrawal. The vignette does not provide enough information to support the diagnosis of generalized anxiety disorder or panic disorder. Further, alcohol use would not be expected to prevent panic attacks or treat anxiety in patients with a generalized anxiety disorder or panic disorder.

• 4

  C. Diagnosis of depression made at least 1 week after patient discontinues drinking

  A 2008 meta-analysis of placebo-controlled trials of antidepressant medications among patients with SUD and depressive disorders by found that diagnosing depression after at least 1 week of abstinence was associated with a greater effect of antidepressant medication treatment. A depressive disorder that persists after 1 week or more of abstinence is likely independent of substance use and should be treated. For patients who cannot achieve any amount of abstinence, the meta-analysis recommended using clinical judgment in making decisions to treat the depressive disorder based on the patient's history, past episodes of independent depression, and severity of the depressive disorder. Further, most positive studies included tricyclic antidepressants or antidepressants with noradrenergic or mixed mechanisms such as serotonin and norepinephrine reuptake inhibitors. Most studies using SSRIs were negative.

• 5

  E. Start an antidepressant medication after this patient completes the medically supervised alcohol detoxification if he remains symptomatic

  In this clinical situation, it is unclear whether this patient's depressive symptoms are substance-induced and likely to resolve spontaneously or represent an independent depressive disorder. Given that there are no acute safety concerns reported, it is not unreasonable to hold off on starting antidepressant medications until they complete alcohol detoxification and withdrawal symptoms subside. When thinking about the psychiatric manifestations of SUD, one has to differentiate between:

  • The substance's expected: Drug and alcohol intoxication or withdrawal cause psychiatric signsss and symptoms that are part of the normal toxidrome of a given substance.

  • Substance induced disorders: This category refers to the presence of psychiatric symptoms that vastly exceed the expected effects of being intoxicated with or withdrawing from a substance and demonstrate symptoms of another psychiatric disorder (psychotic, bipolar, depressive, anxiety, obsessive compulsive, sleep, sexual, or neurocognitive disorder).

  • Co-occurring primary psychiatric disorders: This category refers to psychiatric disorders that either preceded or followed the onset of an SUD, but neither condition played a causative role in the other's onset.

  • Secondary psychiatric disorders: This category refers to psychiatric disorders that follow the onset of an SUD, with the SUD playing a causative role in the onset of the co-occurring psychiatric disorder.

• 6

  A. Increased cardiac workload and systemic vascular resistance

  Cocaine use is associated with significant cardiovascular pathologies that could cause angina and myocardial ischemia. Cocaine causes hypertension, increased systemic vascular resistance, and vasoconstriction. In addition to the standard protocols used for non cocaine-related cardiac events, the medical treatment of cocaine-related angina and myocardial infarction should include benzodiazepines. Benzodiazepines are necessary to manage the hypertension and tachycardia and decrease the central stimulatory effects of cocaine.

  Other causes of cocaine-induced coronary artery disease involve vasculopathy and vasoconstriction. Cocaine use can also cause left ventricular hypertrophy, hyperthrombotic states, aortic dissection and rupture, and arrhythmias.

• 7

  B. Assess the severity of the patient's depression and current suicidal thoughts

  The most important risk factor for suicide is having a history of past suicide attempts. SUD is a major risk factor for attempted and completed suicide. Additionally, acute and severe psychosocial stressors further increase the risk. As a result, this patient presents with a very high risk for suicide and should be evaluated for current suicidal thinking. Ensuring the patient's safety if he is suicidal might require inpatient hospitalization. This patient is certainly at risk of having contracted HIV and HCV. However, laboratory testing for these infections should be offered after acute stabilization and assessment of imminent risks. Having a history of suicide attempts or of obtaining buprenorphine from illicit sources is not a contraindication for treatment with buprenorphine. This patient might benefit from treatment with an SSRI. However, it is preferable to wait until he completes a medically assisted opioid detoxification and reassess his depressive symptoms before prescribing the antidepressant medication.

• 8

  E. Assess the severity of his opioid withdrawal and begin induction with buprenorphine

  This patient is coming to your clinic seeking treatment using medications for opioid use disorder. Given his history of chronic pain and his ongoing pain despite the opioid use, buprenorphine might be a better therapeutic option than naltrexone because of its analgesic effect. Given that he is currently in withdrawal, you might be able to begin the office-based buprenorphine induction on the same day, maximizing the chances for his recovery. In contrast, prescribing him clonidine and other medication support for opioid withdrawal and discharging him with a follow-up appointment in 1 week will increase the likelihood that he will continue using illicit opioids after leaving your office to relieve the withdrawal symptoms. Given the information presented in the vignette, he does not appear to indicate a need for an inpatient admission for detoxification. Further, although having a history of suicide and SUD are major risk factors for suicide, the patient is not currently suicidal or depressed. There is no indication to send him to the psychiatric emergency room.

• 9

  B. Send him to the emergency room

  This patient should be evaluated urgently in an emergency room setting. Given his history of injection drug use, sharing needles, chest pain, fatigue, fever, and tachycardia, he is at elevated risk for infective myocarditis (endocarditis). Injecting drugs increases the likelihood of bacterial injections from nonsterile injection procedures. Additionally, drug and alcohol use are associated with behavioral disinhibition, which could further increase the risk of bacterial infections. Bacteria, most commonly Staphylococcus , can travel with blood and deposit as vegetations on cardiac valves (most commonly the tricuspid valve). Bacterial endocarditis is lethal if untreated. Treatment involves a long course of intravenous antibiotics and at times valve replacement.

• 10

  E. Immediately

  Guidelines recommend starting HAART as soon as possible. There is no recommended CD4 count cutoff at which to initiate therapy. In fact, evidence suggests that starting HAART when CD4 count is high is associated with improved long-term outcomes. HAART is associated with improved CD4 count, virologic suppression, and preserved immune function. Earlier HAART initiation may result in better immunologic responses and clinical outcomes, reductions in AIDS and non–AIDS-associated morbidity and mortality, and a significant reduction in HIV transmission risk. Although it is certainly preferable that patients with HIV abstain from drug and alcohol use, HAART is not contraindicated in patients who are actively using it.

• 11

  D. Brain imaging studies revealed a loss of brain tissue, and cognitive impairments are noted on neuropsychological testing

  Persons of AUD or a chronic history of excessive alcohol use may present with neurocognitive impairment that is detected on neuropsychological testing and brain imaging. Magnetic resonance imaging studies and diffusion tensor imaging reveal a loss of brain tissue with accelerating grey matter loss. In more than half of persons with AUD, abnormalities can be seen on computed tomography imaging even in the absence of cognitive deficits. Some of these changes may be reversible with abstinence suggesting that the abnormalities might at least be in part evidence of brain tissue dehydration.

• 12

  E. Antisocial personality disorder

  SUDs are often comorbid with personality disorders, most commonly, antisocial personality disorder, borderline personality disorder, and schizotypal personality disorder. Of these, antisocial personality disorder is the most common.

• 13

  E. None of the above

  The FDA approves three medications to treat opioid use disorder: buprenorphine, methadone, and naltrexone (both as a daily oral formulation and a long-term injectable formulation). No medication is approved specifically for comorbid opioid use disorder and PTSD. In fact, no medications are approved specifically for any SUD comorbid with any other psychiatric disorder.

CHAPTER 3

• 1

  B. Conditioned place aversion

  Conditioned place preference and self-administration measure the reinforcing effect of a substance and are animal models relevant for the binge/intoxication phase of the addiction cycle. Drug- and cue-induced reinstatement are relevant for the preoccupation/anticipation stage of the addiction cycle.

• 2

  B. NPY

  NPY is a neuromodulator shown to have anxiolytic effects and is part of the brain's “anti-stress” system that functionally opposes CRF. Dynorphin is upregulated in withdrawal states and leads to increased dysphoria. Central noradrenergic systems become activated in withdrawal and increase anxiety and agitation. The HPA axis becomes activated in withdrawal and leads to elevated levels of CRF, ACTH, and glucocorticoids; ACTH does not counteract or modulate the effects of CRF.

• 3

  A. Norepinephrine

  Dopamine is ubiquitously important in directly or indirectly mediating the rewarding effect of all drugs of abuse. Alcohol directly affects GABA, serotonin, and opioid receptors in the binge/intoxication stage. Norepinephrine is the least relevant neurotransmitter system in mediating the rewarding effects of any substance of use. It is most relevant in the withdrawal/negative affect stage in which noradrenergic overactivity in the locus coeruleus is implicated in opioid withdrawal and can be effectively treated with central alpha-agonists such as clonidine or lofexidine.

• 4

  C. Reinforcing drugs will lower the threshold for ICSS

  The Olds and Milner classic experiment was an ICSS animal study showing that animals would perform a response (lever pressing) to self-administer a stimulus delivered via implanted brain electrodes to brain reward circuits. ICSS provides a way to study substances’ effects on brain reward thresholds. The addictiveness of substance is correlated with its ability to lower ICSS threshold. Answer choice A describes conditioned place aversion, and answer choice B describes conditioned place preference.

• 5

  A. Defensive burying

  In defensive burying, the animal is placed in a box filled with woodchip bedding and an electrified probe protruding into the box. After touching the probe and receiving a shock, the animal generally buries the probe with the woodchips; observers will measure variables related to burying including the time to burying, the height of the woodchip mound, and the total time spent burying. These measures are sensitive for increased anxiety-like states. Choices B, C, D, and E do not measure anxiety-like responses.

• 6

  B. Negative reinforcement

  In negative reinforcement, a negative stimulus is removed with a behavior, making it more likely that the behavior will be repeated. In this example, resumption of heroin use reduces opioid withdrawal symptoms. Removal of these highly aversive symptoms is a powerful negative reinforcer.

• 7

  D. Operant conditioning

  Operant conditioning refers to behavior modification through use of punishing and rewarding consequences. Methadone maintenance programs use a contingency management approach through their allotment of take-home doses for patients who have demonstrated abstinence.

• 8

  A. Glutamatergic projections from the PFC to dopamine neurons in the VTA

  Incentive salience refers to cue-learning in which a stimulus becomes conditioned with a drug's rewarding effect, to the point in which the stimulus can induce motivation to drug-seek. Incentive salience is regulated through glutamatergic projections from the PFC to dopamine neurons in the VTA.

• 9

  B. Hallucinogens

  According to data from large surveys of adult twins, hallucinogen use disorder has the lowest heritability among the common substances of abuse, whereas cocaine and opioids have among the highest ( ).

• 10

  A. GWAS

  Answer choice B is an older method used to identify chromosomal regions coinherited with the phenotype of interest (e.g., substance abuse) among related individuals. Linkage studies have largely been replaced by GWAS, which are performed by querying the genome with microarrays of thousands to millions of genetic markers to examine whether particular alleles are more common among individuals with the disease versus controls. Advantages of GWAS include the ability to identify multiple risk alleles with individual small effect sizes, although studies typically require very large sample sizes.

CHAPTER 4

• 1

  A. Her alcohol use is considered at-risk because she is drinking more than the accepted weekly amount for women.

  This question is testing your knowledge of the NIAAA standards of alcohol consumption for men and women. According to the NIAAA, women should drink no more than 7 standard drinks per week and no more than 3 standard drinks per occasion; men should drink no more than 14 standard drinks per week and no more than 4 drinks per occasion. Drinking more than these limits is considered to put individuals at risk for negative health and social outcomes.

• 2

  F. Inpatient; he has no social supports involved in his treatment.

  This question is testing your application of the ASAM placement criteria to determine whether this patient can be managed as an outpatient. In general, patients who present with CIWA greater than 15 (indicating severe withdrawal), have unstable medical or psychiatric conditions that can complicate treatment of withdrawal, have high levels of recent alcohol consumption, have a history of withdrawal seizures or DTs, who do not have any social supports at home or cannot reliably present to an outpatient clinic daily should be managed in the inpatient setting.

• 3

  D. Acamprosate did not outperform either placebo or naltrexone.

  This question is testing your knowledge of the Project COMBINE research study. Disulfiram was not included as one of the study's three interventions, immediately ruling out answer choices B and E. Acamprosate was not associated with a significant reduction in drinking compared with placebo, either alone or in combination with naltrexone at the end of the 16-week treatment period. The treatment group that showed the best outcome received MM with naltrexone without the CBI.

• 4

  D. Patients receiving medication management (naltrexone) + no behavioral intervention

  Of the nine treatment groups compared in the COMBINE study, the groups performing best at the end of the treatment period received medication management (with naltrexone) with and without behavioral intervention, and behavioral intervention with MM (with placebo).

• 5

  F. No group showed statistically superior outcomes at 1-year follow-up.

  According to results from the COMBINE study, all between-group effects observed following the 16-week treatment period were no longer significant at 1-year follow-up.

• 6

  B. Fomepizole prevents build-up of formaldehyde through inhibition of alcohol dehydrogenase.

  To answer this question, you need to know both methanol's metabolic pathway and fomepizole's mechanism of action. Methanol is metabolized to formaldehyde by alcohol dehydrogenase. Ethylene glycol is metabolized to glycolic acid, and ethanol is metabolized to acetaldehyde; neither of these byproducts are in the metabolic pathway of methanol. Fomepizole competitively inhibits ADH, not ALDH, and prevents metabolization of methanol to the highly toxic formaldehyde.

• 7

  A. Production of calcium oxalate crystals, leading to renal injury

  Ethylene glycol is metabolized to glycolic acid, which is further broken down to calcium oxalate. Calcium oxalate crystals can then form in the kidneys, leading to renal injury. Answer choice B refers to the effects of methanol; answer choice C refers to the effects of ethanol; answer choice D refers to the effects of isopropyl alcohol, which causes ketosis without metabolic acidosis.

• 8

  D. EtG

  Indirect biomarkers do not contain ethanol or its direct metabolites and include MCV, CDT, GGT, AST, and alanine aminotranferase. Direct measures include EtG, EtS, BAC, and breath alcohol concentrations.

• 9

  B. Women have a lower expression of ADH in the gastric mucosa, reducing first-pass metabolism.

  Gastric ADH is responsible for first-pass metabolism of alcohol. Women express less gastric ADH, which allows more alcohol to be absorbed into systemic circulation. Gastric ADH expression also declines with advancing age. There is no evidence for answer choice A. Answer choices C and D are true for individuals who express the ALDH*2 and ADH1B*2 isotype, common among those with East Asian heritage.

• 10

  B. Elevated heart rate

  Vital signs are not factored into overall scoring but are typically recorded each time the CIWA-Ar is administered. The decision not to include vital signs was based on data showing that pulse and blood pressure did not correlate as well with severity of alcohol withdrawal compared with the other signs and symptoms included in the CIWA-Ar.

• 11

  C. ALDH; acetaldehyde

  Alcohol flush reaction is common among individuals of East Asian descent because of a higher frequency of both the ADH1B*2 and ALDH2*2 alleles, both of which lead to accumulation of acetaldehyde. The ADH1B*2 allele metabolizes ethanol more rapidly to acetaldehyde, whereas the ALDH2*2 allele metabolizes acetaldehyde more slowly; the presence of one or both of these isotypes would lead to accumulation of acetaldehyde. Increased amounts of acetaldehyde lead to the release of histamines, which then causes vessel dilatation and skin redness.

• 12

  D. Verbal learning

  Some or all of the above cognitive domains have been found to become impaired in 50% to 70% of individuals with AUD. However, verbal learning impairments are most quick to reverse following cessation of use with some studies demonstrating recovery within the first 2 weeks of abstinence. As longer-term abstinence is reached, learning and memory issues are still present in some individuals.

• 13

  D. Liver disease

  In the United States, alcohol-related mortality has alarmingly doubled between 1999 and 2017. This has been the subject of extensive national discussion and was highlighted by recent publications by economists Anne Case and Angus Deaton. These deaths, also coined “deaths of despair,” are primarily a result of liver disease (31%), followed by overdoses (18%) either with alcohol alone or in combination with other drugs, followed by cardiovascular disease (11%) based on mortality data from 2017. Globally, however, alcohol-related injuries (traffic accidents, self-harm, or violence) are the most common cause of alcohol-related mortality.

• 14

  B. Naltrexone

  Naltrexone is the only medication listed that primarily acts by reducing the euphoric and pleasant effects of alcohol by blocking opioid pathways projecting to the reward areas of the brain, thereby reducing alcohol-induced dopamine release and the positive reinforcing effects of alcohol. Disulfiram predominantly works by creating a highly aversive reaction (i.e., a punishment) in the presence of alcohol, thereby incentivizing the patient to avoid it completely. Acamprosate reduces symptoms of protracted withdrawal during abstinence and has no effect on the positive reinforcing effects of alcohol. Sertraline has little efficacy for use in AUD beyond treating a co-occurring psychiatric disorder. Gabapentin has no effects on the positive reinforcing properties of alcohol. Naltrexone is the best choice.

• 15

  C. Acamprosate

  Acamprosate should only be started when the patient has achieved abstinence; because of its GABAergic and antiglutamatergic activity, it is thought to attenuate the symptoms of protracted alcohol withdrawal that place patients at risk for relapse during early abstinence.

• 16

  A. It is a positive allosteric modulator of GABA-A receptors.

  Acamprosate is a positive allosteric modulator of the GABA-A receptor and an NMDA receptor antagonist; it reduces glutamatergic activity and increases GABAergic activity during early abstinence and can counteract the symptoms of protracted withdrawal. Answer choices B and D describe the mechanism of action for baclofen and gabapentin, respectively.

• 17

  D. Alpha-2-receptor agonist

  Gabapentin was designed to be a structural analog of GABA and closely resembles endogenous amino acids; despite this and despite its name, gabapentin does not directly agonize or antagonize the GABA-A or GABA-B receptor and does not modulate GABA activity. Gabapentin inhibits the alpha-2-delta-1 subunit of voltage-gated calcium channels.

• 18

  C. ARND

  This question is testing your knowledge of the diagnostic criteria for FASD. This patient meets criteria for ARND. Generally, the IQ of individuals with FASD is above the threshold for intellectual disability (IQ >70). If this same patient had two or more facial features of FAS, he would meet criteria for pFAS. The diagnosis of FAS requires four criteria: (1) two or more characteristic facial features (short palpebral fissures, thin vermillion border, or smooth philtrum), (2) growth retardation, (3) evidence of brain involvement, and (4) neurobehavioral impairments. Documented alcohol exposure is not required for the FAS diagnosis.

• 19

  C. Coronary occlusion

  Severe myocardial disease or coronary occlusion is an absolute contraindication to disulfiram use; the disulfiram–alcohol reaction can cause coronary vasospasm, chest pain, and in rare cases can cause cardiorespiratory death. Hepatic impairment is a relative but not absolute contraindication; disulfiram can cause a fatal drug-induced hepatitis in 1 in 30,000 patients, and increases risk for cholestatic and fulminant hepatitis. Physiological dependence on opioids is a contraindication for using naltrexone but not disulfiram. Depression (severe or otherwise) and migraines are not contraindications for using disulfiram.

• 20

  B. High neuroticism

  AUD is significantly associated with higher neuroticism and lower conscientiousness. It is not associated with differences in extraversion, openness to experience, or agreeableness.

• 21

  D. Acamprosate

  The FDA approved three medications to treat AUD: disulfiram, naltrexone, and acamprosate. Of these, acamprosate would be the preferred medication to use in patients with hepatic insufficiency. It is excreted in urine as an unmetabolized drug. As a result, it should not be used as a first-line agent for renal impairment patients. Naltrexone is metabolized hepatically via noncytochrome-mediated dehydrogenase and is subject to the extensive first-pass effect. Its use can be associated with increase serum transaminases, and it is contraindicated in patients with acute hepatitis or hepatic failure. Disulfiram is metabolized hepatically via glucuronidation. Its side effects include cholestatic hepatitis, fulminant hepatitis, and hepatic failure. It is relatively contraindicated in patients with hepatic cirrhosis. Gabapentin and ondansetron are used as second-line treatment options for AUD but are not FDA approved for this condition.