JASON Z.W. POWERS, MD, MAPP, DABAM, DABFM. Alcohol Screening and Interventions for the Family Physician

Transcription

1 JASON Z.W. POWERS, MD, MAPP, DABAM, DABFM Alcohol Screening and Interventions for the Family Physician

2 SPEAKER DISCLOSURE Dr. Powers has disclosed that he has no actual or potential conflict of interest in relation to this topic.

3 LEARNING OBJECTIVES By the end of this activity, the participant should be better able to: Discuss screening instruments for detecting alcohol abuse and dependence and define moderate drinking and take a history of alcohol use. Describe clinical characteristics of alcohol abuse, dependence, intoxication, and withdrawal. Learn the latest pharmacological treatment options for the treatment of alcohol addiction. Learn the psychiatric and medical co-morbidities associated with the disease of alcohol addiction.

4 QUESTION 1 What does CPT code stand for and what s the average reimbursement? 1. Individual psychotherapy, insight oriented, behavior modifying a/o supportive, 30 min with the patient and/or family member $ Individual psychotherapy, insight oriented, behavior modifying a/o supportive, 30 min with the patient and/or family member $ Therapeutic counseling of a person and extended family who is suspected of maybe perhaps having a drink or two $ No such code exists, nobody gets paid to treat those types of people $0.00

5 EDUCATIONAL OBJECTIVES 1. Screening instruments, moderate drinking & taking a history

6 PRIMARY CARE SCREENING & COUNSELING

7 SBIRT SBIRT: Screening, Brief Intervention & Referral to Treatment Screening A healthcare professional assesses a patient for risky substance use behaviors using standardized screening tools. Screening can occur in any healthcare setting Brief Intervention A healthcare professional engages a patient showing risky substance use behaviors in a short conversation, providing feedback and advice Referral to Treatment A healthcare professional provides a referral to brief therapy or additional treatment to patients who screen in need of additional services

8 QUESTION 2 A 23-year-old male sees you after his wife made an appointment for him because his blood pressure was 152/95 mm Hg at a health fair they recently attended. A brief history leads you to screen him for alcohol abuse, particularly for heavy episodic drinking. Screening approaches with good evidence of high sensitivity and specificity for hazardous drinking include all of the following except? 1. The single question, How many times in the past year have you had 5 or more drinks in a day? 2. The single question, When was the last time you had more than 5 drinks in one day? 3. The 3-question AUDIT-C 4. The 4-question CAGE 5. The 10-question AUDIT

9 Primary care validation of a single screening question for drinkers. Seale JP1, Boltri JM, Shellenberger S, Velasquez MM, Cornelius M, Guyinn M, Okosun I, Sumner H. RESULTS: Among 625 drinkers interviewed, 25.6% were at-risk drinkers, 21.7% had a current alcohol- use disorder, and 35.2% had either or both conditions. Considering "within the last 3 months" as positive, the sensitivity of the single question was 80% and the specificity was 74%. Chi-square analyses revealed similar sensitivity across ethnic and gender groups; however, specificity was higher in women and whites (p =.0187 and.0421, respectively). Considering "within the last 12 months" as positive increased the question's sensitivity, especially for those with alcohol-use disorders. The area under the receiver operating characteristic curve of the single alcohol screening question (0.79) was slightly lower than for the AUDIT and AUDIT-C, but sensitivity and specificity were similar. CONCLUSIONS: A single question about the last episode of heavy drinking is a sensitive, time-efficient screening instrument that shows promise for increasing alcohol screening in primary care practices.

10 J Gen Intern Med Jul;24(7): doi: /s Epub 2009 Feb 27. Primary care validation of a single-question alcohol screening test. Smith PC1, Schmidt SM, Allensworth-Davies D, Saitz R. Author information Erratum in J Gen Intern Med Apr;25(4):375. Abstract BACKGROUND: Unhealthy alcohol use is prevalent but under-diagnosed in primary care settings. OBJECTIVE: To validate, in primary care, a single-item screening test for unhealthy alcohol use recommended by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). DESIGN: Cross-sectional study. PARTICIPANTS: Adult English-speaking patients recruited from primary care waiting rooms. MEASUREMENTS: Participants were asked the single screening question, How many times in the past year have you had X or more drinks in a day?, where X is 5 for men and 4 for women, and a response of 1 or greater [corrected] is considered positive. Unhealthy alcohol use was defined as the presence of an alcohol use disorder, as determined by a standardized diagnostic interview, or risky consumption, as determined using a validated 30-day calendar method. MAIN RESULTS: Of 394 eligible primary care patients, 286 (73%) completed the interview. The single-question screen was 81.8% sensitive (95% confidence interval (CI) 72.5% to 88.5%) and 79.3% specific (95% CI 73.1% to 84.4%) for the detection of unhealthy alcohol use. It was slightly more sensitive (87.9%, 95% CI 72.7% to 95.2%) but was less specific (66.8%, 95% CI 60.8% to 72.3%) for the detection of a current alcohol use disorder. Test characteristics were similar to that of a commonly used three-item screen, and were affected very little by subject demographic characteristics. CONCLUSIONS: The single screening question recommended by the NIAAA accurately identified unhealthy alcohol use in this sample of primary care patients. These findings support the use of this brief screen in primary care.

11 Primary care validation of a single screening question for drinkers. Seale JP1, Boltri JM, Shellenberger S, Velasquez MM, Cornelius M, Guyinn M, Okosun I, Sumner H. Abstract OBJECTIVE: The aim of this study was to conduct a primary care validation study of a single screening question for alcohol misuse ("When was the last time you had more than X drinks in 1 day?," where X was four for women and X was five for men), which was previously validated in a study conducted in emergency departments. METHOD: This cross-sectional study was accomplished by interviewing 625 male and female adult drinkers who presented to five southeastern primary care practices. Patients answered the single question (coded as within 3 months, within 12 months, ever, or never), Alcohol Use Disorders Identification Test (AUDIT), and AUDIT consumption questions (AUDIT-C). Alcohol misuse was defined as either at-risk drinking, identified by a 29-day Timeline Followback interview or a current (past-year) alcohol-use disorder by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, or both.

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14 The value of the CAGE in screening for alcohol abuse and alcohol dependence in general clinical populations: a diagnostic meta-analysis. Aertgeerts B1, Buntinx F, Kester A. RESULTS: We identified 35 articles using the DSM criteria as the gold standard to test the diagnostic value of the CAGE. Only 10 studies could be included for the meta-analysis. With a cutoff point > or =2, the pooled sensitivity is far better in inpatients (0.87) than in primary care patients (0.71) or ambulatory patients (0.60). The pooled specificity also differs for each group. The likelihood ratios seem to be relatively constant over the populations (overall LR+:3.44;LR-:0.18). We calculated a pooled AUC of 0.87 (95% CI ). At low specificity values, the sensitivity was homogeneous over the studies, and at a low sensitivity, the specificity was heterogeneous. CONCLUSION: The diagnostic value of the CAGE is of limited value using this test for screening purposes at a recommended cutpoint of > or =2.

15 QUESTION 3 What do the letters C-A-G-E represent in the CAGE Questionnaire? 1. Cut out the drinking. I m Angry at you for drinking. Go fly a kite. Exit my presence please. 2. Have you tried to Cut down the drinking? Are you Annoyed when others ask you to quit? Do you feel Guilty over drinking? Do you need an Eye opener? 3. Have you tried Cutting yourself? Can you Apply for disability? Have you considered Going out of the country? Why are you still Engaged in drinking? 4. Cowabunga. Astrophysics. Guile. Eyeball.

16 CAGE Questions 1. In the last 12 months, have you felt you should cut down on your drinking? 2. In the last 12 months, has anyone annoyed you by criticizing your drinking? 3. In the last 12 months, have you felt guilty or bad about how much you drink? 4. In the last 12 months, have you been waking up wanting to have an alcoholic drink to steady your nerves or get rid of a hangover (eyeopener)?

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19 Use of Family CAGE-AID questionnaire to screen the family members for diagnosis of substance dependence. Basu D1, Ghosh A1, Hazari N1, Parakh P1. Abstract BACKGROUND & OBJECTIVES: CAGE-AID - short, useful substance dependence screening tool Screening one family member for substance dependence (family) - clinical & research Assess the validity of the Family CAGE-AID

20 Use of Family CAGE-AID questionnaire to screen the family members for diagnosis of substance dependence. Basu D1, Ghosh A1, Hazari N1, Parakh P1. METHODS: Cross-sectional assessments using CAGE-AID and Family CAGE-AID questionnaires were conducted both for the study participants (n = 210) and their family members. The participants were recruited from two different treatment settings: a treatment seeking population from a de-addiction centre, and non-treatment seekers for substance use disorders from the psychiatry outpatient department. ICD-10 criteria and subsequent detailed clinical interview by a trained psychiatrist were used for the final diagnosis of substance dependence. RESULTS: In the psychiatry outpatient group, the scores on CAGE-AID and Family CAGE-AID questionnaires were significantly correlated with the ICD-10 symptom score (r=0.81 and 0.70, respectively). In the same group, inter-rater agreement of the Family CAGE-AID was good with CAGE-AID and moderate with ICD-10 diagnosis of substance dependence (Cohen's kappa 0.78 and 0.61, respectively). A cut-off score of three on Family CAGE-AID was found to be 95 8 per cent sensitive and 100 per cent specific.

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23 Use of Family CAGE-AID questionnaire to screen the family members for diagnosis of substance dependence. Basu D1, Ghosh A1, Hazari N1, Parakh P1. INTERPRETATION & CONCLUSIONS: Family CAGE-AID - valid screening instrument for the diagnosis of substance dependence Acceptable sensitivity and specificity of a cut-off score of three The simplicity and the brevity of such an instrument can be valuable in the clinical settings of developing countries and also for epidemiological studies

24 EDUCATIONAL OBJECTIVES 2. Clinical characteristics of alcoholism, intoxication & withdrawal

25 QUESTION Which one of the following is a true statements about alcohol withdrawal? 1. The Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA Ar), has been validated for assessing withdrawal severity 2. Serial measurements of pulse and blood pressure are sufficient for monitoring the course of alcohol withdrawal 3. When used alone for treating alcohol withdrawal, neuroleptics such as haloperidol are as effective as benzodiazepines 4. Among the benzodiazepines, lorazepam is preferable to diazepam if liver disease is suspected 5. Timing benzodiazepine doses based on monitoring of withdrawal severity leads to a shorter course of pharmacotherapy for withdrawal, compared with giving the benzodiazepine on a set schedule 6. Gabapentin is not an effective treatment for alcohol withdrawal

26 THE ACUTE ALCOHOL WITHDRAWAL SYNDROME Objective assessment of the severity of alcohol withdrawal the Clinical Institutes Withdrawal Assessment-Alcohol Revised (CIWA-Ar) scale In a patient diagnosed to have alcohol withdrawal syndrome, the CIWA-Ar can be used to measure its severity. The scale is not a diagnostic tool as it has not been found to be useful in differentiating between DT and delirium due to medical illnesses.

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28 Clinical management of alcohol withdrawal: A systematic review Shivanand Kattimani and Balaji Bharadwaj Department of Psychiatry, Regional Deaddiction Center, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India Address for correspondence: Dr. Balaji Bharadwaj, Department of Psychiatry, Regional Deaddiction Center, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry , India. ni.ude.rempij@b.ijalab Abstract This article reviewed evidence for appropriate clinical management 4 meta-analyses, 9 systematic reviews, 26 review articles & more Alcohol withdrawal syndrome - commonly encountered clinical diagnosis Varies in severity Complicated alcohol withdrawal presents with hallucinations, seizures or DTs Benzodiazepines have the best evidence base Evidence favors symptom-monitored loading for severe withdrawals initial dose guided by risk factors for complicated withdrawals further dosing guided by withdrawal severity Supportive care and use of vitamins

29 Clinical Management of Alcohol Withdrawal: A systematic Review Alcoholism may first manifest when a person develops withdrawal symptoms after stopping alcohol - either due to family pressure, self-motivation, physical ill health or difficulty in procuring alcohol. It is a common misconception among regular drinkers that stopping alcohol causes more problems than continuing it. This may be partly true in those who have developed dependence as they may experience withdrawal symptoms including autonomic arousal, hallucinations, seizures and delirium tremens (DT). Since many people underplay or minimize their drinking behavior, they tend to develop withdrawal symptoms when hospitalized for other physical problems and not for alcoholism forming a substantial part of consultation-liaison psychiatry.

30 ALCOHOL-INDUCED PHYSIOLOGICAL CHANGES Ordinarily, the excitatory (glutamate) and inhibitory (GABA) neurotransmitters are in a state of homeostasis.

31 ETHANOL GABAA Receptor GABA glutamate NMDA receptor

32 ALCOHOL-INDUCED PHYSIOLOGICAL CHANGES Alcohol is a central nervous system (CNS) depressant, influencing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).

33 ALCOHOL-INDUCED PHYSIOLOGICAL CHANGES Alcohol is a central nervous system (CNS) depressant, influencing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Alcohol facilitates GABA action, causing decreased CNS excitability

34 GABA tone & Glutamate tone sedation, incoordination, & cognitive impairment

35 ALCOHOL-INDUCED PHYSIOLOGICAL CHANGES GABA down regulated causes a decrease in the number of GABA receptors (down regulation)

36 ALCOHOL-INDUCED PHYSIOLOGICAL CHANGES This results in the requirement of increasingly larger doses of ethanol to achieve the same euphoric effect, a phenomenon known as tolerance. GABA down regulated Causes a decrease in the number of GABA receptors (down regulation)

37 THE ACUTE ALCOHOL WITHDRAWAL SYNDROME Making a Diagnosis of Alcohol Withdrawal Syndrome True or False? The alcohol withdrawal syndrome is diagnosed when the following two conditions are met. A clear evidence of recent cessation or reduction of alcohol after repeated and usually prolonged and/or high-dose use. The patient shows symptoms of alcohol withdrawal that are not accounted for by a medical disorder or by another mental or behavioral disorder. 1. TRUE 2. FALSE

38 ALCOHOL-INDUCED PHYSIOLOGICAL CHANGES Alcohol mediated CNS inhibition is reduced and the glutamate mediated CNS excitation is left unopposed, resulting in a net CNS excitation

39 ALCOHOL-INDUCED PHYSIOLOGICAL CHANGES This CNS excitation results in the clinical symptoms of alcohol withdrawal in the form of autonomic over activity such as tachycardia, tremors, sweating and neuropsychiatric complications such as delirium and seizures. Alcohol mediated CNS inhibition is reduced and the glutamate mediated CNS excitation is left unopposed, resulting in a net CNS excitation

40 GABA tone & Glutamate tone tremor, anxiety, seizures

41 GABA tone & Glutamate tone tremor, anxiety, seizures

42 TABLE 1 COMMON SIGNS AND SYMPTOMS OF ALCOHOL WITHDRAWAL SYNDROME SIGNS SYMPTOMS

43 THE ACUTE ALCOHOL WITHDRAWAL SYNDROME When the onset of withdrawal like symptoms or delirium is after 2 weeks of complete cessation of alcohol, the diagnosis of alcohol withdrawal syndrome or DT becomes untenable, regardless of frequent or heavy use of alcohol.

44 TABLE 2 CLINICAL DESCRIPTIONS OF ALCOHOL WITHDRAWAL SYNDROMES BY SEVERITY

45 THE ACUTE ALCOHOL WITHDRAWAL SYNDROME Differential diagnosis of DT Delirium - clinical syndrome: Acute onset Altered sensorium: Disorientation Perceptual abnormalities illusions & hallucinations Confused or disordered thinking Psychomotor agitation (or retardation) with Disturbed (usually reversed) sleep-wake cycle

46 THE ACUTE ALCOHOL WITHDRAWAL SYNDROME Differential diagnosis of DT DT is a specific type of delirium occurring in alcohol withdrawal states associated with: Psychomotor agitation (hyperactive delirium) In cases of hypoactive delirium comorbid hepatic encephalopathy, hyponatremia or other medical illnesses must be ruled out.

47 TABLE 3 DIFFERENTIAL DIAGNOSIS FOR ALCOHOL WITHDRAWAL DELIRIUM

48 PREDICTORS OF SEVERE ALCOHOL WITHDRAWAL (WITHDRAWAL SEIZURE OR DT) A history of sustained drinking A history of previous DT Age greater than 30 The presence of a concurrent illness The presence of significant alcohol withdrawal in the presence of an elevated alcohol level A longer period since the last drink (i.e., patients who present with alcohol withdrawal more than two days after their last drink are more likely to experience DT than those who present within two days)

49 Neurocircuitry & Neurophysiology Drives The Treatment of Alcoholism prefrontal cortex VTA Nucleus Accumbens & Arcuate Nucleus

50 TREATMENT OF ACUTE ALCOHOL WITHDRAWAL SYNDROME Detoxification Wean from a psychoactive substance Safe and effective manner Gradually tapering or substituting Minimizes the withdrawal symptoms Prevents complications and Hastens the process of abstinence

51 TREATMENT OF ACUTE ALCOHOL WITHDRAWAL SYNDROME Detoxification General supportive care Quiet room with low lighting & minimal stimulation Seizures or DT necessitate immediate IV access IM lorazepam Adequate sedation Fluid and electrolyte imbalances Adequate nutrition Prevent aspiration

52 TREATMENT OF ACUTE ALCOHOL WITHDRAWAL SYNDROME Medication of choice for detoxification In 1969, a landmark study by Kaim et al., proved beyond doubt that chlordiazepoxide (a benzodiazepine) was far better in preventing seizures and DT in patients with alcohol withdrawal compared to chlorpromazine, hydroxyzine, thiamine or placebo.

53 TREATMENT OF ACUTE ALCOHOL WITHDRAWAL SYNDROME Medication of choice for detoxification In 1969, a landmark study by Kaim et al., proved beyond doubt that chlordiazepoxide (a benzodiazepine) was far better in preventing seizures and DT in patients with alcohol withdrawal compared to chlorpromazine, hydroxyzine, thiamine or placebo. Evidence is strongly in favor of the use of benzodiazepines to treat alcohol withdrawal states.

54 TREATMENT OF ACUTE ALCOHOL WITHDRAWAL SYNDROME The dose of benzodiazepine required per day can be calculated according to the average daily alcohol intake. An estimate of the amount of alcohol consumption is given by the following formula: Alcohol (in g) = Volume of liquor (ml) (%) ethanol content in the liquor (w/v)

55 TREATMENT OF ACUTE ALCOHOL WITHDRAWAL SYNDROME Medication of Choice for Detoxification The percentage of alcohol in various liquors is: Beer (standard) 3-4%, Beer (strong) 8-11%, Wines 5-13%, Fortified wines 14-20%, Spirits/Indian Made Foreign Liquor like (rum/whiskey/gin/vodka/brandy) 40%, Arrack 33%. One standard drink contains about 10 g of absolute alcohol or ethanol

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57 Treatment regimens used in alcohol withdrawal states Fixed dose regimen - best suited for out-patient 4 divided 5 mg of diazepam equivalents is prescribed for every standard drink consumed Sedative hypnotics remain the agents of choice Co-morbidities After 2-3 days of stabilization taper off over 7-10 days Advise risks and when to reduce the dose

58 Treatment regimens used in alcohol withdrawal states Loading dose regimen Sellers and Manikant - efficacy of an 20 mg diazepam oral loading dose q 2 h Withdrawal severity CIWA-Ar and clinical condition monitored before each dose Reduces: Risk of complications Total dose of benzodiazepines needed Duration of withdrawal symptoms Loading dose - use long acting benzodiazepines - self-tapering effect

59 Symptom-triggered treatment (STT) Saitz et al. - chlordiazepoxide given when CIWA-Ar > 8 Requires close in-patient monitoring Choose appropriate patients No stupor or other nonverbal state No h/o w/d seizure

60 Symptom-triggered treatment (STT) Decreases DTX duration & BZD dose compared with fixed dose regimen. Useful in patients who have never had complicated withdrawals.

61 Symptom-monitored loading dose (SML)? past history of seizures or DT? current clinical status If acute medical illness or a Hx of severe withdrawals, then 20 mg diazepam immediately Diazepam (20 mg) q 2 h until CIWA-Ar scores < 10

62 Symptom-monitored loading dose (SML) SML combines principles & advantages of STT Accounts for hx of severe withdrawals Loading dose regardless of symptoms

63 Rapid loading with close monitoring Recommended only in patients with DT Frequent boluses of IV diazepam until pt is calm & sedated

64 MANAGEMENT OF MINOR ALCOHOL WITHDRAWAL SYNDROME May not need pharmacotherapy Supportive care in a calm & quiet environment Observation - up to 36 h* With risk factors - single 20 mg diazepam loading dose immediately & monitor pt Out-patient treatment for low risk, clinically stable patients

65 MANAGEMENT OF MINOR ALCOHOL WITHDRAWAL SYNDROME Pharmacotherapy started when: BP > 150/90 mmhg Temp > 37.7 C HR > 100 Other w/d sxs: Agitation Insomnia Tremulousness

66 MANAGEMENT OF MODERATE TO SEVERE ALCOHOL WITHDRAWAL Without seizures or DT Immediately start its on SML Monitor CIWA-Ar & clinical sxs of tachycardia and hypertension Fixed dose regimen if adequate trained personnel are not available or if outpatient

67 SEVERE ALCOHOL WITHDRAWAL WITH ALCOHOL WITHDRAWAL SEIZURES Sz = Severe IV lorazepam 2 mg with current Sz or PMHx + Give SML diazepam mg Prevent DTs Inpatient monitoring for at least 72 h

68 SEVERE ALCOHOL WITHDRAWAL WITH ALCOHOL WITHDRAWAL SEIZURES Thorough neurological & general medical evaluation In new onset seizures consider brain imaging Neurological consultation: > six seizures during alcohol withdrawal Seizures persisting for more than 6 h Presence of focal seizures/change in seizure type History of traumatic brain injury Family history of seizures in relatives who do not use alcohol Status epilepticus Focal neurological deficits Presence of meningeal irritation Patients with worsening sensorium

69 SEVERE ALCOHOL WITHDRAWAL WITH DTS Goal-calm, but awake state or light somnolence IV diazepam - frequent intervals with close monitoring IV/IM lorazepam with hepatic disease, pulmonary disease or elderly (risk of over-sedation & respiratory depression) Initial 10 mg diazepam IV then 10 mg q 5-20 min Increase to 20 mg if the first 2 doses don't calm the patient down Once light somnolence is achieved shift to SML

70 SEVERE ALCOHOL WITHDRAWAL WITH DTS No trials of rapid loading with diazepam in DTs Trial comparing loading doses of barbiturates (versus diazepam loading), where the drug is given at 2 h intervals Trial of diazepam (loading dose versus fixed doses) for management of DTs In practice, loading dose strategy (20 mg diazepam every 2 h) can be safely administered in DTs Vital signs guide treatment in DT-plus condition (DT in presence of medical comorbidities) as falsely high CIWA-Ar scores fail to trigger a proper loading-dose regimen

71 REFRACTORY DT > than 50 mg Diazepam in the 1 st h or > 200 mg within the 1 st 3 hrs with poor control of w/d sxs Rule out medical or neurological causes of delirium Oral or IV loading with phenobarbital mg/h Barbiturates also GABA-enhancing & have been tested in a double-blind protocol against diazepam Risk of over-sedation - elderly or hepatic disease Risk of respiratory depression - pulmonary disease No antidote to barbiturate toxicity Haloperidol mg IM q min or 2-20 mg/h with diazepam mg every 1-2 h Newer antipsychotics like risperidone (1-5 mg/day) or olanzapine (5-10 mg/day) better safety profile & preferred as adjuncts to benzodiazepine treatment

72 IMPORTANCE OF ADJUNCTIVE SUPPLEMENTS (VITAMIN B AND MAGNESIUM) Wernicke's Encephalopathy (WE) - chronic thiamine deficiency. Confusion, ataxia and ophthalmoplegia Undiagnosed in nearly 90% of the cases Mortality - 20% 75% developing a permanent severe amnestic syndrome (Korsokoff's encephalopathy) Thiamine mg thiamine daily for the first 3-5 days With suspected WE, thiamine 500 mg/day for 3-5 days If clinical improvement - continue for total of 2 weeks Multivitamin supplements (B1 + B2 + B6 + nicotinamide + Vitamin C + Magnesium) for the initial 3-5 days

73 EDUCATIONAL OBJECTIVES 1.SDRAWAL. 3. PHARMACOLOGICAL TREATMENT OPTIONS 4. PSYCHIATRIC & MEDICAL CO-MORBIDITIES

74 QUESTION How many FDA-approved medications are indicated for treating alcoholism? 1. None 2. Two 3. Three 4. Five 5. Eight

75 QUESTION A 26-year-old female who is one of your patients was admitted to your service last night with jaundice, ascites, and abdominal pain. You last saw her about a year ago, and she has a history of heavy drinking for several years. In addition to treating her liver failure you also attempt to address her alcohol dependence. You tell her that medication might help her stop drinking, and she expresses an interest in trying this. She would also like to try to reconnect with her counselor and her Alcoholics Anonymous group. Which one of the following would be most appropriate for this patient? 1. Acamprosate 2. Disulfiram 3. Lorazepam 4. Naltrexone 5. Sertraline

76 Alcoholism: FDA Approved Medications Three oral medications: (1) Naltrexone (2) Acamprosate (3) Disulfiram One injectable medication: (1) Extended-release injectable naltrexone

77 EDUCATIONAL OBJECTIVES PHARMACOLOGICAL TREATMENT OPTIONS Neurocircuitry & Neurophysiology Drive Alcoholism Treatment Medications & Psychosocial Therapy Are Combined For Maximal effectiveness For whom is pharmacotherapy appropriate?

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79 NEUROCIRCUITRY & NEUROPHYSIOLOGY DRIVE ALCOHOLISM TREATMENT ALCOHOLISM IS A REWARD DEFICIT DISORDER Reward neurotransmission is compromised Reward systems are hypoactive during acute withdrawal Remain hypoactive with repeated withdrawal & during protracted abstinence Anti-reward neurotransmission is recruited Brain stress systems are activated during acute withdrawal Sensitize with repeated withdrawal & remain activated during protracted abstinence.

80 ETHANOL THE REWARD PATHWAY BETA ENDORPHIN RELEASE POTENTIATED dopamine Nucleus Accumbens VTA

81 ANTI-Reward Transmitters Implicated in the Motivational Effects of Alcohol Negative Hedonic Effects Dopamine dysphoria Opioid peptides... pain Serotonin dysphoria GABA anxiety, panic attacks

82 GABA & Glutamatergic Medications Reduce craving & relapse related to alcohol withdrawal (both acute & protracted) Reduce reward & habitual/ compulsive drinking

83 GABA tone & Glutamate tone restlessness, craving & discontentment stabilizes cell membranes

84 GABA tone & Glutamate tone restlessness, craving & discontentment stabilizes cell membranes Acamprosate

85 Acamprosate vs. Placebo: Meta-analysis 7 studies, Treatment n=1195, Control n=1027 Bouza, C. et al. Addiction 2004;99:811

86 Acamprosate vs. Placebo: Meta-analysis Weighted mean difference favoring acamprosate Bouza, C. et al. Addiction 2004;99:811

87 Acamprosate vs. Placebo: Meta-analysis 27 days (95% CI 18 days, 36 days), p< Bouza, C. et al. Addiction 2004;99:811

88 Acamprosate vs. Placebo: Meta-analysis Proportion of patients continuously abstinent for 1 year Acamprosate 23% Placebo 15% Bouza, C. et al. Addiction 2004;99:811

89 QUESTION 4 True statements about acamprosate include which of the following EXCEPT? 1. It is effective for maintaining abstinence from alcohol after withdrawal is complete 2. It is superior to naltrexone for maintaining abstinence from alcohol 3. Nausea is a common side effect 4. Diarrhea is a common side effect

90 ACAMPROSATE CLINICAL TRIALS 17 clinical trials 36% abstinent vs 23% on placebo Better results in European trials

91 DOPAMINE REWARD PATHWAY dopamine + Alcohol stimulates µ- opioid receptors REWARD PLEASURE EUPHORIA

92 Neurocircuitry & Neurophysiology Drive The Treatment of Alcoholism prefrontal cortex Nucleus Accumbens & Arcuate Nucleus + - VTA

93 NALTREXONE BLOCKS ΜU-OPIOID RECEPTOR µ-opioid receptors dopamine receptors endorphins

94 QUESTION True statements regarding the use of naltrexone for treating alcohol dependence include all of the following except? 1. It reduces the risk of returning to any drinking in newly abstinent patients 2. It reduces the risk of relapse to heavy drinking 3. The benefits of treatment for 6 months or longer have been shown to be superior to those of treatment lasting less than 6 months 4. The number needed to treat for one patient to benefit is 9 5. The major side effect is nausea

95 Evidence for reduced cravings and relapse rates 23% relapsed vs. 54% placebo during 12 week study

96 Opioid antagonists for alcohol dependence. Rösner S1, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M. Author information Abstract BACKGROUND: Alcohol dependence belongs to the globally leading health risk factors. Therapeutic success of psychosocial programs for relapse prevention is moderate and could be increased by an adjuvant treatment with the opioid antagonists naltrexone and nalmefene. OBJECTIVES: To determine the effectiveness and tolerability of opioid antagonists in the treatment of alcohol dependence. SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2010 and inquired manufacturers and researchers for unpublished trials. SELECTION CRITERIA: All double-blind randomised controlled trials (RCTs) which compare the effects of naltrexone or nalmefene with placebo or active control on drinking-related outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently extracted outcome data. Trial quality was assessed by one author and cross-checked by a second author. MAIN RESULTS: Based on a total of 50 RCTs with 7793 patients, naltrexone reduced the risk of heavy drinking to 83% of the risk in the placebo group RR 0.83 (95% CI 0.76 to 0.90) and decreased drinking days by about 4%, MD (95% CI to -2.04). Significant effects were also demonstrated for the secondary outcomes of the review including heavy drinking days, MD (95% CI to -0.99), consumed amount of alcohol, MD (95% CI to -1.97) and gammaglutamyltransferase, MD (95% CI to -1.75), while effects on return to any drinking, RR 0.96 (95 CI 0.92 to 1.00) missed statistical significance. Side effects of naltrexone were mainly gastrointestinal problems (e.g. nausea: RD 0.10; 95% CI 0.07 to 0.13) and sedative effects (e.g. daytime sleepiness: RD 0.09; 95% CI 0.05 to 0.14). Based on a limited study sample, effects of injectable naltrexone and nalmefene missed statistical significance. Effects of industry-sponsored studies, RR 0.90 (95% CI 0.78 to 1.05) did not significantly differ from those of non-profit funded trials, RR 0.84 (95% CI 0.77 to 0.91) and the linear regression test did not indicate publication bias (P = 0.765). AUTHORS' CONCLUSIONS: Naltrexone appears to be an effective and safe strategy in alcoholism treatment. Even though the sizes of treatment effects might appear moderate in their magnitudes, these should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.

97 Naltrexone Naltrexone can reduce alcohol "liking" and craving. Naltrexone 12.5 mg/d-->25 mg/d-->50 mg/d Main contraindication: opiates, pregnancy Main side effects: nausea, dizziness

98 Naltrexone Naltrexone can reduce alcohol "liking" and craving." On average, one out of nine patients was helped by naltrexone.

99 Naltrexone: Vulnerability Naltrexone reduces tolerance to opioids In turn, use of opioids could result in potentially lifethreatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.)

100 Naltrexone: Contraindications Receiving opioid analgesics Current physiologic opioid dependence In acute opioid withdrawal Who have failed the naloxone challenge test or have a positive urine screen for opioids Hypersensitivity to naltrexone, polylactidecoglycolide (PLG), carboxymethylcellulose, or any other components of the diluent

101 NALTREXONE DEPOT INJECTION: SAFETY & SIDE EFFECTS Hepatotoxicity** Nausea Vomiting Injection site reactions Muscle cramps Injection site reactions Eosinophilic Pneumonia Hypersensitivity Reactions

102 THE SINCLAIR METHOD

103 Disulfiram ADH Acetaldehyde Flushing Headache Palpitations Dizziness Nausea ALDH acetyl CoA CO 2

104 Disulfiram Interferes with alcohol metabolism Increases aldehyde concentrations results in flushing, nausea, vomiting Poor compliance is typical Better use prior to and during in short-term high-risk situations

105 Disulfiram: Contraindications & Side Effects

106 Medications & Psychosocial Therapy Usually combined Naltrexone & primary care management (PCM) vs. naltrexone & cognitive behavioral therapy (CBT) Comparable results for initial 10 weeks, results favored PCM thereafter Naltrexone (vs. placebo) without obligatory therapy was as effective in treating alcohol dependence

107 Recovery = Abstinence The immediate goal of reducing alcohol use is necessary but rarely sufficient for the achievement of the longer-term goals of improved personal health & social function. (McLellan A.T., McKay J.R., Forman R., Cacciola J., Kemp J., 2005)

108 Medication Appropriate for Some All people with alcohol dependence who are: Currently drinking Experiencing craving At risk for return to drinking or heavy drinking

109 Medications for Alcohol Dependence Combining Medications and Behavioral Interventions (COMBINE) clinical trial Benefit medications/counseling combined Medications usually prescribed 6-12 months

110 Considerations: Specific medication contraindications Willing to engage in psychosocial support/therapy Relationship/willingness to follow-up with provider Outpatient or inpatient setting access to monitoring (follow-up visits, liver enzymes, outcome metrics)

111 EDUCATIONAL OBJECTIVES 1.SCRT OPTIONS 4. PSYCHIATRIC & MEDICAL CO-MORBIDITIES

112 SEVERE ALCOHOL WITHDRAWAL WITH DTS No trials of rapid loading with diazepam in DTs Trial comparing loading doses of barbiturates (versus diazepam loading), where the drug is given at 2 h intervals (Kramp P, Rafaelsen OJ. Delirium tremens: A double-blind comparison of diazepam and barbital treatment. Acta Psychiatr Scand. 1978;58: ) Trial of diazepam (loading dose versus fixed doses) for management of DTs (Wasilewski D, Matsumoto H, Kur E, Dzikliñska A, WoŸny E, Stencka K, et al. Assessment of diazepam loading dose therapy of delirium tremens. Alcohol Alcohol. 1996;31: ) In practice, loading dose strategy (20 mg diazepam every 2 h) can be safely administered in DTs Vital signs guide treatment in DT-plus condition (DT in presence of medical comorbidities) as falsely high CIWA-Ar scores fail to trigger a proper loading-dose regimen (Bharadwaj B, Bernard M, Kattimani S, Rajkumar RP. Determinants of success of loading dose diazepam for alcohol withdrawal: A chart review. J Pharmacol Pharmacother. 2012;3:270 2.)

113 OVERALL OUTCOME PREDICTORS Psychiatric Co-morbidity Substance Related Problems Polysubstance Abuse Length of Treatment Monitoring Genetic Socio-Economic

114 PHARMACOTHERAPY FOR MOOD AND ANXIETY DISORDERS Insufficient evidence to suggest their use in patients without mood disorders SSRIs citalopram & fluvoxamine Treatment of patients with co-existing psychiatric symptoms & disorders improves outcomes Anxiety: Buspirone Depression: Fluoxetine

115 Pharmacotherapy for Alcoholism: What Gives? No Skill In A Pill