management of alcohol withdrawal and dependence: … of unhealthy management of unhealthy alcohol...

Management of Unhealthy Management of Unhealthy Alcohol Use:Alcohol Use:

From Research to PracticeFrom Research to Practice

Richard Saitz, MD, MPH, FACPRichard Saitz, MD, MPH, FACPProfessor of Medicine & EpidemiologyProfessor of Medicine & Epidemiology

Boston University Schools of Medicine & Public HealthBoston University Schools of Medicine & Public HealthBoston Medical CenterBoston Medical Center

Opportunities to talkOpportunities to talk about alcoholabout alcohol

Esophageal cancerEsophageal cancerChronic Chronic pancreatitispancreatitisCirrhosis and chronic hepatitisCirrhosis and chronic hepatitisLip, oral cavity, pharynx, larynx Lip, oral cavity, pharynx, larynx

cancercancerAcute Acute pancreatitispancreatitisPulmonary tuberculosisPulmonary tuberculosisHepatic neoplasmHepatic neoplasmEsophageal, stomach, duodenal Esophageal, stomach, duodenal

diseasesdiseasesHypertensionHypertensionCerebrovascularCerebrovascular

diseasediseaseMedication interactionsMedication interactionsRenal failureRenal failureMedical conditions worseningMedical conditions worseningFetal harmFetal harmCirrhosisCirrhosisAlcoholismAlcoholism

AtrialAtrial

fibrillation (holiday heart)fibrillation (holiday heart)CardiomyopathyCardiomyopathyHypertensionHypertension

NutritionalNutritionalMalnutritionMalnutritionThiamine and Thiamine and folatefolate

deficiencydeficiencyEndocrine/MetabolicEndocrine/Metabolic

OsteoporosisOsteoporosisMagnesium, calcium, potassium, phosphorusMagnesium, calcium, potassium, phosphorusHypoHypo--

and hyperglycemiaand hyperglycemiaAcidosesAcidoses

(primary and secondary, due to ingestions(primary and secondary, due to ingestionsImpaired fertility (men and women) and sexual funImpaired fertility (men and women) and sexual funAnemia (Anemia (folatefolate, toxic, iron, chronic disease, , toxic, iron, chronic disease, hemolyhemolyPancytopeniaPancytopeniaCoagulopathyCoagulopathy

HepatitisHepatitis

Toxic (alcohol, acetaminophen)Toxic (alcohol, acetaminophen)CirrhosisCirrhosis

AscitesAscites

and edemaand edemaCoagulopathyCoagulopathy

and bleedingand bleedingSpontaneous bacterial peritonitis, EncephalopathySpontaneous bacterial peritonitis, EncephalopathyHepatomaHepatoma

GastrointestinalGastrointestinalGI bleeding: GI bleeding: varicesvarices, Mallory, Mallory--Weiss, gastritis, ulcerWeiss, gastritis, ulcerEsophagitisEsophagitis, gastritis, gastritisEsophageal stricture, malignancyEsophageal stricture, malignancyGastric cancerGastric cancerMalabsorptionMalabsorption

and diarrhea, with or withoutand diarrhea, with or without……PancreatitisPancreatitis

(acute and chronic)(acute and chronic)Social problemsSocial problemsStrokeStrokeViolent deathViolent death

InfertilityInfertilityTremorTremorEcchymosis/purpuraEcchymosis/purpuraPalmarPalmar

erythemaerythemaScars from traumaScars from traumaGynecomastiaGynecomastiaHepatomegalyHepatomegalySpidersSpidersUric acid, glucoseUric acid, glucoseMCV, AST, HDL, GGTMCV, AST, HDL, GGTHeartburnHeartburnGastrointestinal upsetGastrointestinal upsetAM cough or HAAM cough or HAAnxiety, stressAnxiety, stressInsomniaInsomniaConcentrationConcentrationMemoryMemory


TachycardiaTachycardiaHypertensionHypertension

ApneaApneaImpaired gagImpaired gagCoughCoughMyopathyMyopathyGoutGoutRhabdomyolysisRhabdomyolysisKidney failureKidney failure

Pneumonia, lung abscessPneumonia, lung abscessTBTBCentral nervous system infectionCentral nervous system infection

DiabetesDiabetesPneumoniaPneumoniaHypokalemiaHypokalemiaHypomagnesemiaHypomagnesemiaHypocalcemiaHypocalcemiaIntoxication, blackouts, overdoseIntoxication, blackouts, overdoseWithdrawal seizuresWithdrawal seizuresHead trauma and Head trauma and subduralsubdural

hematomahematomaSensory, motor or autonomic neuropathySensory, motor or autonomic neuropathyWernickeWernicke’’ss

syndromesyndromeKorsakoffKorsakoff’’ss

((amnesticamnestic) syndrome) syndromeCerebellarCerebellar

degenerationdegenerationStroke (hemorrhagic, ischemic)Stroke (hemorrhagic, ischemic)MarchiafavaMarchiafava--BignamiBignami

(corpus (corpus callosumcallosum))Confusion, language, dementia, seizuresConfusion, language, dementia, seizuresBreast cancerBreast cancerDepressionDepression


A caseA case

For your useFor your useDemonstrates common medical consequencesDemonstrates common medical consequences

CaseCaseA 43 year old man presents with A 43 year old man presents with epigastricepigastric

discomfort and vomiting for 1 day.discomfort and vomiting for 1 day.Breath alcohol is 210 mg/Breath alcohol is 210 mg/dLdL

(0.21 (0.21

g/100mL).g/100mL).

Presenter

Presentation Notes

This stuff you know and love but it is an example of a case you can use to teach---think about how you might teach the material…better!

Case (continued)Case (continued)He fell in the kitchen and bumped his head.He fell in the kitchen and bumped his head.He reports no He reports no hematemesishematemesis, , hematocheziahematochezia, ,

melenamelena, tremors, past seizures, liver disease, , tremors, past seizures, liver disease, gastrointestinal bleeding, gastrointestinal bleeding, pancreatitispancreatitis

or or

delirium.delirium.He lives alone and reports drinking all day since He lives alone and reports drinking all day since

he became disabled from lumbar disc disease he became disabled from lumbar disc disease ten years ago. He takes no medications, has ten years ago. He takes no medications, has no allergies, and smokes one pack of no allergies, and smokes one pack of cigarettes daily.cigarettes daily.

Case (continued)Case (continued)

T 98, RR 20, HR 110 (regular), BP 110/82 T 98, RR 20, HR 110 (regular), BP 110/82 standing, 96, 140/70 lying down.standing, 96, 140/70 lying down.

Unable to visualize Unable to visualize fundifundi, EOMI, supple neck, , EOMI, supple neck, clear chest, no murmur, mild clear chest, no murmur, mild epigastricepigastric

tenderness, no tremor, frontal tenderness, no tremor, frontal ecchymosisecchymosis..He is awake, alert and oriented to place, time He is awake, alert and oriented to place, time

and person. Speech is fluent. Gait normal. and person. Speech is fluent. Gait normal. SensorimotorSensorimotor

exam nonexam non--focal.focal.

Initial laboratory studies are pending.Initial laboratory studies are pending.

IntoxicationIntoxication

Is he intoxicated (legal versus medical)?Is he intoxicated (legal versus medical)?What is your initial management?What is your initial management?

Intoxication (DSMIntoxication (DSM--IV)IV)

Reversible, substanceReversible, substance--specific, recent ingestionspecific, recent ingestionSignificant behavioral or psychological changes Significant behavioral or psychological changes due to CNS effect during or shortly after usedue to CNS effect during or shortly after use


Four hours later (15Four hours later (15--20 mg/20 mg/dLdL/hr [1 drink] /hr [1 drink] elimination), the patient becomes tremulous, elimination), the patient becomes tremulous, anxious, and continues to have nausea. BP anxious, and continues to have nausea. BP 134/84, HR 90, ethanol level 146 mg/dl.134/84, HR 90, ethanol level 146 mg/dl.

What is the diagnosis?What is the diagnosis?What is appropriate management?What is appropriate management?

Presenter

Presentation Notes

Resume detail here

Alcohol Withdrawal(DSM-IV)

•

Cessation or reduction in alcohol use that has been heavy and prolonged

•

Two or more of the following, developing in hours to days, causing distress or impairment, not due to other condition–

Autonomic hyperactivity (sweating, tachycardia)

–

Increased hand tremor–

Insomnia

–

Nausea or vomiting–

Transient tactile, visual or auditory hallucinations or illusions

–

Psychomotor agitation–

Anxiety

–

Grand mal seizures

GABAA

Receptor

NMDA receptor

Glycine

Receptor

ETHANOL

VOCCL,N

Ca+ +

GABA

glutamate

CNS Neuron

Cl-

Cl-

Ca++NO

Benzodiazepines vs. Placebo Benzodiazepines vs. Placebo Outcome: SeizuresOutcome: Seizures

Sereny

1965, Kiam

1969, Zilm

1980, Sellers 1983, Naranjo

1983,summarized in Mayo-Smith MF & ASAM Working Group JAMA 1997;278:144-51

ANY

1/188 (0.5%)Placebo

16/201 (8%)

RRR 93%, p<0.001

Presenter

Presentation Notes

Can we prevent Sz? Mike Mayo-Smith, who some of you at the VA may now know as the director of ambulatory care for the Northeast region, and I led a work group for the American Society of Addiction Medicine to develop an evidence summary and practice guideline for the management of alcohol withdrawal. This slide summarizes the results of the 5 randomized trials in the literature. Benzodiazepines reduced the incidence of seizures during alcohol withdrawal from 8% to 0.5%, a 93% reduction. 3 studies CDZ, 1 DIAZ, 1 LORAZ N=378

Benzodiazepines vs. Placebo Benzodiazepines vs. Placebo Outcome: DeliriumOutcome: Delirium

Chlordiazepoxide 3/172 (2%)

Placebo

11/186 (6%)

RRR 71%, p=0.04Rosenfeld 1961, Sereny

1965, Kaim

1969, Zilm

1980, summarized in Mayo-Smith MF & ASAM Working Group JAMA 1997;278:144-51

Presenter

Presentation Notes

Can we prevent delirium? Based on the 4 randomized trials in the literature, all using chlordiazepoxide, benzodiazepines decreased the incidence of delirium tremens or DTs from 6% to 2%, a 71% reduction. So, benzodiazepines are proven to prevent the 2 most serious complications of alcohol withdrawal. What about alcohol itself?? N=358, All CDZ vs PLA

Alcohol WithdrawalAlcohol Withdrawal AlcoholAlcoholProsPros

The perfect crossThe perfect cross--tolerant drugtolerant drugThe alcoholicThe alcoholic’’s drug of choices drug of choice

ConsConsTwo controlled trials: in one (Gower 1980), more DTs and Two controlled trials: in one (Gower 1980), more DTs and seizures c/w seizures c/w chlordiazepoxidechlordiazepoxide; in the only ; in the only RRCT (Spies 1995) no CT (Spies 1995) no diff c/w diff c/w benzo+haloperidolbenzo+haloperidol or or clonidineclonidineNarrow toxic to therapeutic indexNarrow toxic to therapeutic indexMany toxicities (hepatitis, gastritis, Many toxicities (hepatitis, gastritis, pancreatitispancreatitis, marrow , marrow suppression...)suppression...)Need to monitor and adjust levelsNeed to monitor and adjust levelsReinforces acceptability and continued useReinforces acceptability and continued use

Presenter

Presentation Notes

(SEE SLIDE) As stated in published national practice guidelines, alcohol should not be used to manage alcohol withdrawal. So, …the evidence supports BZDs, to reduce the incidence of seizures and delirium. How should we be administering these BZDs?

SymptomSymptom--triggered Therapytriggered Therapy

101 adults with no past seizures hospitalized for 101 adults with no past seizures hospitalized for alcohol withdrawalalcohol withdrawalPlacebo or Placebo or ChlordiazepoxideChlordiazepoxide 50 mg 50 mg qidqid X4 then X4 then 25 mg 25 mg qidqid X8 (doubleX8 (double--blind)blind)ALL: ALL: ChlordiazepoxideChlordiazepoxide 2525--100 mg q 1 hour as 100 mg q 1 hour as needed (objective scale: CIWAneeded (objective scale: CIWA--ArAr) )

Saitz R et al JAMA 1994;272:519-23

Presenter

Presentation Notes

The traditional fixed schedule dose (write order and return in several days) is the bane of AW mgt, but was standard until relatively recently. But there are often concerns of benzodiazepine overdose precipitating respiratory failure, as well as the converse, “ya didn’t treat ‘em soon enough and he went into DTs….) We decided to challenge the standard with a regimen that would deliver enough, but not too much medication. We tested symptom-triggered therapy in a study of 101 adults with no past seizures hospitalized for alcohol withdrawal. They were randomized to placebo or chlordiazepoxide 50 mg qid the first day, followed by a 2 day taper, in a double blind fashion. All subjects got chlordiazepoxide 25-100 mg every 1 hour as needed as determined by an objective withdrawal severity scale, known as the CIWA-Ar. (By the way, I just heard yesterday of a malpractice suit that is going to trial because an objective severity measure was not used in treating a man with alcohol withdrawal who died of respiratory arrest.)

Saitz R et al JAMA 1994;272:519-23

Decreased Duration of TreatmentDecreased Duration of Treatment

Presenter

Presentation Notes

Median 9 hours vs 68 hours—see graph Median 100 mg vs 425 mg No difference in withdrawal severity, hallucinations, seizures, delirium, leaving AMA or readmission This regimen addresses the concerns of avoiding undertreatment and overtreatment of alcohol withdrawal, and suggests that symptoms can guide our treatment in most cases. One caution in applying these results is that the study was done on an inpatient hospital unit but it was a detox unit not a medical service, and patients with seizures, which can occur without warning symptoms, were excluded. Because patients with seizures and acuter medical illness are at risk of more severe withdrawal, they should all receive at least one dose of benzodiazepine even if they are asymptomatic.

ASAM

Practice Guidelines Treatment approaches

•

Monitor

q 4-8 hrs until symptoms improved

•

Symptom-triggered

(q 1 when CIWA>8)

•

Chlordiazepoxide

50-100 mg•

Diazepam 10-20 mg

•

Lorazepam

2-4 mg•

Fixed schedule

(q 6 for 4/8 doses + PRN)

•

Chlordiazepoxide

50 mg/25 mg•

Diazepam 10 mg/5 mg

•

Lorazepam

2 mg/1 mgMayo-Smith and ASAM working group JAMA 1997;278:144-51Saitz and O’Malley Med Clin

N A 1997;81:881-907


The patient is seen having a generalized tonicThe patient is seen having a generalized tonic-- clonicclonic

convulsion.convulsion.

What is the most likely etiology?What is the most likely etiology?What is the appropriate workWhat is the appropriate work--up?up?

Alcohol Withdrawal Seizures: Diagnosis

•

Recurrent detox

and prior seizure are risk factors•

Occur 24-48 hrs after abstinence or decreased intake

•

Often occur prior to autonomic hyperactivity•

Generalized, single or a few (79% <3, <3% status), over a short time (86%/1st 6 hrs)

•

Fever, delirium, focal exam, head trauma, focal or multiple seizures, 1st seizure ever, or status suggest other diagnoses

•

CT scanning unhelpful if clinical picture consistentVictor & Brausch. Epilepsia

1967;8:1, Feussner

et al. Ann Int

Med 1981;94:519, Lechtenberg

1990

Seizure Recurrence•

186 subjects with alcohol withdrawal seizures

•

RPCDBT•

2 mg of lorazepam

IV•

Also decreased hospital admission

3

24

0

10

20

30

40

50

lorazepam

% with2ndseizure

D'Onofrio G et al. N Engl

J Med 1999;340:915-919.


The patient tells you he is at the racetrack with his The patient tells you he is at the racetrack with his friends, BP 170/100, HR 110, Temp 99.friends, BP 170/100, HR 110, Temp 99.

What is the diagnosis?What is the diagnosis?What if he were febrile?What if he were febrile?

Alcohol Withdrawal DTs: Treatment

•

N=34, RCT•

Diazepam 10 mg IV then 5mg q 5”

vs. paraldehyde 30cc

PR q 30”

until calm but awake•

All complications in paraldehyde group– sudden death (2), apnea (2), brachial plexus injury (2),

3rd floor jump attempt (1), bitten nurse (1), bitten intern (1)

•

Diazepam 200 mg mean dose requiredThompson, Maddrey, Osler Medical Housestaff. Ann Int Med 1978;82:175

Presenter

Presentation Notes

An oldie but a goodie

Outpatient DetoxificationOutpatient DetoxificationRCT: Inpatient versus outpatient (med RCT: Inpatient versus outpatient (med ctrctr))InpatientInpatient

Meds, AA, and social, recreational counselingMeds, AA, and social, recreational counselingOutpatientOutpatient

Daily evaluation, review of meds, counselingDaily evaluation, review of meds, counselingBoth: Both: oxazepamoxazepam 30 mg 30 mg qidqid and and hshs (all PRN) (all PRN) ((‘‘round the clock if seizure history)round the clock if seizure history)

until minimal symptoms, negative BAC, and until minimal symptoms, negative BAC, and <<30 mg 30 mg oxazepam/24 hrsoxazepam/24 hrs

Hayashida

et al. NEJM 1989;320:358

Presenter

Presentation Notes

Past DTs 20-23% Past withdrawal seizures 30-34% 68-70% living with family Outpatient group slightly less severe WD symptoms 14 yrs heavy drinking

RCT OutcomesRCT Outcomes

*p<0.001, **p<0.03Hayashida et al. NEJM 1989;320:358

Completing treatment (%)*

72

95Days of treatment (mean)*

4.5

9.2

Cost ($)*

175-388

3319-3665

Abstinence (1 month)(%)**

66

81No Intoxication (1 month)(%)*

76

88

Abstinence (6 months)(%)

48

46No Intoxication (6 mo)(%)

59

51

OUT(N=87)

IN (N=77)

Alcohol WithdrawalAlcohol Withdrawal SettingsSettings

OutpatientOutpatientLast drink >36 hrs: symptoms unlikely to developLast drink >36 hrs: symptoms unlikely to developNo other risk factors, responsible otherNo other risk factors, responsible other

Consider inpatientConsider inpatientPast seizure, drug use, anxiety disorder, multiple Past seizure, drug use, anxiety disorder, multiple detoxifications, alcohol >150 (risks more severe symptoms) detoxifications, alcohol >150 (risks more severe symptoms)

InpatientInpatientOlder age (>60), concurrent acute illness, seizure, moderate Older age (>60), concurrent acute illness, seizure, moderate to severe symptoms (risks DTs)to severe symptoms (risks DTs)

ICU levelICU levelDTsDTs

Presenter

Presentation Notes

No symptoms if less than 3 years No seizures or DTs if <6 years Consider if time discussing patient selection, medication, monitoring

Management of Unhealthy Alcohol UseManagement of Unhealthy Alcohol Use

Detoxification is not treatmentDetoxification is not treatmentBrief InterventionBrief Intervention

TreatmentTreatmentCounselingCounselingPharmacotherapyPharmacotherapy

Self and mutual helpSelf and mutual help

Presenter

Presentation Notes

Counseling: MI covered elsewhere—many done by spec but we will talk later re that which we can do AA covered elsewhere---recommend to all with dep. 12 step facil (counsel) similar efficacy to other rx’s Psychological, medical, employment, legal, social services Removal from drinking environment Motivational Disease model (12 step) Cognitive-behavioral Cue exposure Contingency management Coping skills Marital and family therapy Psychotherapy NTX (short and long) ACAMP DS

What?-10-15 minutes-Feedback-Advice-Goal Setting-Follow-up

Ingredients of Successful Brief Ingredients of Successful Brief InterventionsInterventions

How?-Empathy-Self-efficacy-Menu

Presenter

Presentation Notes

What is effective? Brief multicontact (meaning more than once) 5-15 minute discussions that include feedback of personal risk (GGT, etc), Clear advice (best medical), and goal setting achieved by negotiating with the patient. This should be done while demonstrating empathy (by demonstrating that you are listening), supporting self efficacy, and providing a menu of options. The goal for people with dependence is linkage to additional care (and the efficacy of BI for this group is less well established); for nondependent drinking it is a change towards less risky use. these risky drinkers can be thought of and addressed much like we think of and treat hypercholesterolemia. High cholesterol is a risk factor for heart disease much like risky drinking is a risk factor for breast cancer, and motor vehicle crashes. And when we identify hypercholesterolemia, we address it with behavioral interventions, and even add pharmacotherapy. Risky drinking can initially be addressed with education that it is a risk factor. For people with more consequences, as with hypercholesterolemia unresponsive to education, behavioral and pharmacological treatments are indicated. ((Elicit—provide—elicit. Goal set based on readiness. Talk about readiness.))

Proportion of drinkers of risky amounts Proportion of drinkers of risky amounts decreased from 69% (942/1374) to 57% decreased from 69% (942/1374) to 57% (810/1410)(810/1410)Consumption decreased 15% (by 38 grams Consumption decreased 15% (by 38 grams [about 3 standard drinks] per week)(n=5639)[about 3 standard drinks] per week)(n=5639)

Efficacy of Brief Intervention

Beich

et al. BMJ 2003;327:536Bertholet

et al. Arch Intern Med.

2005;165:986

Presenter

Presentation Notes

Note—numbers in thousands, not tens or hundreds as for drug studies in other diseases 11 systematic reviews and meta-analyses Generally for nondependent risky drinkers. Goal for dependence is linkage to treatment and abstinence.

RCT, 17 practices, 64 physiciansRCT, 17 practices, 64 physiciansN=774N=774

Men >14 drinks/wkMen >14 drinks/wkWomen >11 drinks/wkWomen >11 drinks/wk

93% 12 month follow93% 12 month follow--upupControl: health bookletControl: health bookletIntervention: health booklet + 2 10Intervention: health booklet + 2 10--1515”” physician physician discussions and a followdiscussions and a follow--up nurse phone callup nurse phone call

Treatment in Medical Settings: Treatment in Medical Settings: Project Project TrEATTrEAT

Fleming MF, Lawton Barry K, et al. JAMA 1997;277:1039

Presenter

Presentation Notes

Here is a representative study of treatment in outpatient medical settings. This is Michael Fleming’s study out of the U of Wisconsin, called Project Treat, or the Trial of early alcohol treatment. It was a randomized controlled trial in 17 private practices, with 64 physicians and 774 men drinking more than 14 drinks per week and women drinking more than 11 drinks per week. They had 93% follow-up at 12 months. The control group got a health booklet. The intervention group got the same health booklet, but also got 2 10-15 minute physician discussions and a follow-up nurse phone call.

Control before/after

Intervention before/after

Drinks/7d* 19/16 (-18%) 19/12 (-40%)

Binges/30d* 5/4 (-21%) 6/3 (-46%)

Hosp days* 42/146 (+248%) 93/91 (-1%)

Project Project TrEATTrEAT

ResultsResults

*p<0.001

Fleming MF, Lawton Barry K, et al. JAMA 1997;277:1039

Presenter

Presentation Notes

Both groups decreased their drinking as is usual in these studies, but the intervention group cut their weekly and binge drinking by around 40%, about twice as much as the control group. Hospital utilization stayed the same in the intervention group but increased in the control group. There have been approx 3 dozen other brief treatment studies in many settings with similar results. Some of these show decreases in GGT, alcohol-related medical conditions, and one found a decrease in mortality.

Cost of intervention: $166 per patient (includes patient costs)

Net benefit: $546 in medical costs, $7780 if societal costs included (mainly motor vehicle)

*36 months. >20 drinks (men), >13 drinks (women) per weekFleming MF et al. Alcohol Clin

Exp Res. 2002;26(1):36-43.

At 4 yearsAt 4 years…… ControlControl InterventionIntervention

Hospital Days (p<0.05)Hospital Days (p<0.05) 663663 420420

ED Visits (p<0.08)ED Visits (p<0.08) 376376 302302

Risky Drinking* (p<0.001)Risky Drinking* (p<0.001) 35%35% 23%23%

Efficacy and Cost of Advice TrEAT

Long-term Follow-up

Presenter

Presentation Notes

Healthier Drinking Less Saved money MALMOE STUDY (Kristenson H, et al. Alcohol Clin Exp Res 1983;7:203) 48% of all deaths alcohol-related Fewer sick days in intervention group at 4 yrs Lower mortality in intervention group (10% vs. 14%) at 13 years

The Malmö

StudyPopulation-based cohort of middle-aged men identified by screening with upper decile GGT as isolated abnormality and at least 20 g alcohol dailyRandomized to

GGT + RN q mo, MD q 3 moletter—GGT is high, restrict alcohol, F/U in 2 years

78% follow-up (4 years)

Kristenson

H, et al. Alcohol Clin

Exp Res

1983;7:203

Presenter

Presentation Notes

earliest, landmark study 46-49 y.o. male population of Malmö 76% (8,859) screened 796 upper decile GGT 473 with isolated abnormality and at least 20g alcohol/day enrolled, 22% dropout intervention: control:

5-year hospital utilization decreased by 50% in 5 years (total approx. 1600 vs 800 days, mainly alcohol-related)Sick days decreased in intervention groupGGT decreased in both groups (4 yrs)16-year mortality decreased in intervention group

Total mortality: 10% vs. 14% (NS)Alcohol-related (48% of all deaths): 4% vs. 7% (p=0.03)

The Malmö

Study

Kristenson

H, et al. Alcohol Clin

Exp Res

1983;7:203

Presenter

Presentation Notes

Later report had randomized 667 men. 365 (10% total mort) in intervention compared to 302 (14% total mort) in control. NS. Additional 311 controls (14% total mort) followed. 10-16 yr mortality. ARD mortality P val is from HR Cox PH model adjusted for Age. HR with one control group only was 1.9 (1.0-3.8), for all 3 groups was 2.0 [1.1-3.6]. P .026. Alc rel deaths (48% of deaths alc-rel.).3.8% vs 7.3%

Brief intervention in inpatients

Systematic review6 controlled studies identified

1,494 patients; orthopedic, medicine, surgery servicesDecreased alcohol consumption: 0/6Decreased problems: 3/5Decreased serum GGT: 2/3

Emmen

MJ et al. BMJ, doi:10.1136/bmj.37956.562130.EE, 16 Jan 2004

Presenter

Presentation Notes

ED studies not so promising. Trauma setting---1 study of bord signif on trauma recidivism and a recent Schermer study with decr MVC in adj but not adj analysis

Medical InpatientsMedical Inpatients Recent Additional EvidenceRecent Additional Evidence

Brief intervention may be necessary but not enoughBrief intervention may be necessary but not enoughMost patients identified by screening have dependenceMost patients identified by screening have dependenceMixed evidence regarding decrease in drinkingMixed evidence regarding decrease in drinkingSome evidence increased likelihood of referral and Some evidence increased likelihood of referral and readiness to changereadiness to changeStepped care approachStepped care approach……

Saitz et al. Ann Intern Med 2007;146:167-76Freyer-Adam J et al. Drug Alcohol Depend 2008.Bischoff G et al. Drug Alcohol Depend 2008.

Presenter

Presentation Notes

The intervention was not significantly associated with receipt of alcohol assistance by 3 months among alcohol-dependent patients (adjusted proportions receiving assistance, 49% for the intervention group and 44% for the control group; intervention–control difference, 5% [95% CI, –8% to 19%]) or with drinks per day at 12 months among all patients (adjusted mean decreases, 1.5 for patients who received the intervention and 3.1 for patients who received usual care; adjusted mean group difference, –1.5 [CI, –3.7 to 0.6]).

Case

A 53 year old woman drinks ½

to 1 pint of vodka daily and wishes to quit. She has a history of

EGD-proven esophagitis, and has had recurrent hematemesis

after drinking. She has no current

acute medical problem. You are seeing her as an outpatient after hospital discharge. She feels she will drink even though she realizes she will bleed

again. She refuses “inpatient rehab.”

Maintenance and RelapseAnticipate difficult situations (triggers)Emphasize prior successes and use relapse as a learning experience, cope w/cravingHelp patient develop a plan to manage early relapsesFacilitate involvement in treatment (12-step groups, counseling, pharmacotherapy, comorbidpsychiatric disorders)

Friedmann

PD, Saitz R, Samet JH. JAMA 1998;279(15):1227-31.

Presenter

Presentation Notes

Can do this in PC

Patient Selection for Pharmacotherapy

All people with alcohol dependence who are:currently drinkingexperiencing craving or at risk for return to drinking or heavy drinking

ConsiderationsSpecific medication contraindicationsWillingness to engage in psychosocial support/therapyRelationship/willingness to follow-up with health providerOutpatient or inpatient clinical setting with prescriber, access to monitoring (e.g. visits, liver enzymes)

Presenter

Presentation Notes

For whom is pharmacotherapy appropriate? For all people with alcohol dependence who are currently drinking, or who are experiencing craving or who are at-risk for return to drinking or heavy drinking. Considerations include, in addition to patient acceptance, any specific medication medication contraindications, patient willingness to engage in psychosocial support/therapy, your relationship with the patient and their willingness to follow-up, and a setting for clinical care delivery in which it is feasible to prescribe and monitor the medication.

Ethanol AcetateAcetaldehyde•Flushing•Headache•Palpitations•Dizziness•Nausea

ADH

ALDH

Disulfir

am

Disulfiram

Fuller RK et al. JAMA 1986;256:1449

Presenter

Presentation Notes

An old standby for alcoholism treatment since the 1940s has been disulfiram, an inhibitor of aldehyde dehydrogenase, ALDH, that results in increased levels of acetaldehyde and an unpleasant reaction after consumption of ethanol. In one of the largest studies of this medication, disulfiram was no better than placebo in achieving abstinence. But it is not clear that a placebo controlled trial is the best way to test a drug whose efficacy depends on the patient knowing that they may experience a very unpleasant reaction. Of note, in post hoc analyses, the drug was more effective in those who were adherent to it. (Fuller RK et al. JAMA 256:1449, 1986)

Monitored Disulfiram: Randomized studies

Length of follow-up was as follows: Gerrein

1973: 8 weeks; Azrin

1976: 2 years, Azrin

1982: 6 months; Liebson

1978: 6 months.

* Thirty-day abstinence at 6 months

Length of follow-up was as follows: Gerrein

1973: 8 weeks; Azrin

1976: 2 years, Azrin

1982: 6 months; Liebson

1978: 6 months.

* Thirty-day abstinence at 6 months

Author, Yr Follow-up Disulfiram Abstinence

Gerrein, 1973 85%, 39%

Monitored

Unmonitored40%7%

Azrin, 1976 90% Monitored

Unmonitored90-98%55%

Azrin, 1982 100% Monitored

Unmonitored73%*47*

Liebson, 1978 78% Monitored

Unmonitored98%79%

Presenter

Presentation Notes

In controlled studies, 4 trials have shown significantly improved abstinence rates when disulfiram is taken under direct monitoring by a concerned other.

Prescribing

Helping Patients Who Drink Too MuchNIAAA, 2007

Helping Patients Who Drink Too MuchNIAAA, 2007

Presenter

Presentation Notes

Pharmacotherapies for alcohol dependence are no more difficult to prescribe than antidepressants. However, a decade since the approval of naltrexone and more than 50-60 years since the availability of disulfiram, pharmacotherapy has not been used extensively for alcoholism. What are the main prescribing issues? See the handout for details on prescribing all three FDA-approved medications for alcohol dependence.

Prescribing Disulfiram

Main contraindications: recent alcohol use, pregnancy, rubber, nickel or cobalt allergy, cognitive impairment, risk of harm from disulfiram--ethanol reaction, drug interactionsMain side effects: hepatitis, neuropathy

Disulfiram

250 mg/d-->500 mg/dDisulfiram

250 mg/d-->500 mg/d

Presenter

Presentation Notes

Of all of the approved, efficacious medications, disulfiram may be the most difficult to use since it is an aversive therapy that works best when its administration is monitored. Disulfiram should be started at 250 mg a day, up to a dose of 500 mg. The drug can be used daily or just prior to risky situations, and it lasts 4-7, and up to 14 days. Tell the monitor and the patient they are to take the medication as prescribed. The monitor should observe the patient as he or she takes the pill and call you if the patient is non-adherent. The main contraindications are recent alcohol use, pregnancy, rubber, nickel cobalt allergy, cognitive impairment (since awareness of the risk of the reaction is essential), and as a relative contraindication, conditions that would increase the risk of harm from the disulfiram ethanol reaction, for example, coronary artery disease, esophageal varices. Disulfiram also has numerous drug interactions, including warfarin and anticonvulsants. The main side effect is an idiosyncratic sometimes fulminant hepatitis, and neuropathy seen at higher doses. Regular monitoring of liver enzymes is advised, as is a clear recommendation to avoid alcohol even in over-the-counter medications.

Acamprosate

Stabilizes activity in the glutamate systemStabilizes activity in the glutamate system

NMDA receptor

ETHANOL

glutamate

CNS Neuron

CNS NeuronGABAA

ReceptorGABA

Cl-

Presenter

Presentation Notes

Acamprosate is another FDA approved pharmacotherapy for alcohol dependence. The exact relevant mechanism of action is unclear. The drug is a gamma-amino-butyric acid, or GABA analogue, and it has also been suggested that it modulates action in the NMDA (N-methyl-D-aspartate) glutamate system. Alcohol is an agonist at inhibitory GABA receptors, and an inhibitor of excitatory glutamatergic receptors. It may work by reducing symptoms of protracted abstinence such as insomnia, anxiety and restlessness.

Acamprosate vs. Placebo 7 studies, Treatment n=1195, Control n=1027Weighted mean difference favoring acamprosate

27 days (95% CI 18 days, 36 days), p<0.00001Proportion of patients continuously abstinent for one year

Acamprosate 23%, Placebo 15%

Efficacy of Acamprosate

Bouza C et al. Addiction 2004;99:811Bouza C et al. Addiction 2004;99:811

Presenter

Presentation Notes

This meta-analysis summarizes randomized placebo controlled trials comparing acamprosate with placebo in people with alcohol dependence. Subjects were abstinent for 5-30 days when they started treatment. The meta-analysis summarized results of 7 trials in over 2000 subjects. Acamprosate increased the cumulative duration of abstinence by 27 days. It also was associated with an increase in the proportion of patients with continuously abstinent for a year from 15 to 23%.

Main contraindication: renal insufficiencyMain side effect: diarrhea; pregnancy category C

Prescribing Acamprosate

Acamprosate

666 mg tidAcamprosate

666 mg tid

Presenter

Presentation Notes

Acamprosate is dosed three times a day, 666 mg. The main issue with Acamprosate is that it is contraindicated in renal insufficiency (Cr CL <30 ml/min, half dose for 30-50 ml/min) and its main side effect is diarrhea. Acamprosate and all other alcohol dependence pharmacotherapies are pregnancy category C, meaning that there are no controlled studies in pregnant women, and that they should be prescribed during pregnancy only if clearly needed and the benefits are likely to outweigh the risks.

The RewardPathway

The RewardPathway

Ethanol

DopamineDopamine

Beta endorphin release potentiated

Beta endorphin release potentiated

Naltrexone

prefrontal cortex

nucleus accumbens

VTA

Firing

Presenter

Presentation Notes

Despite the myriad actions of alcohol in the central nervous system, all drugs of abuse including alcohol work by affecting the same reward pathway, that connects the ventral tegmental area or VTA to the nucleus accumbens, where dopamine is released, and the prefrontal cortex. Other neurotransmitters are also involved, including endogenous opioids released as a result of dopamine surges.

Efficacy of Naltrexone

14 studiesRelapse to heavy drinking

Naltrexone 428/1142 (37%), Control 445/930 (48%)

p<0.00001

Odds Ratio (favoring naltrexone)0.62 (95% CI 0.52,0.75)

Bouza

C et al. Addiction 2004;99:811Bouza

C et al. Addiction 2004;99:811

Presenter

Presentation Notes

Naltrexone blocks opioid receptors, including receptors for endogenous opioids. Since these receptors are in part responsible for feelings of pleasure during drinking, naltrexone blocking these receptors makes drinking less pleasurable. For this reason, rather than abstinence, the clinical trials of this drug have focused on relapse or return to heavy drinking rather than total abstinence. This meta-analysis included 14 clinical trials, in which relapse was decreased significantly, from 48% to 37%. The odds ratio favored naltrexone, 0.62, suggesting a 38% decrease in heavy drinking. In one study, patients were not abstinent before beginning naltrexone. In another study, the drug was effective in a primary care setting. In a third study, naltrexone was effective for reducing heavy drinking in nondependent heavy drinkers. In a fourth study, the combination of naltrexone and acamprosate was as safe and more effective than either alone.

InjectableInjectable

NaltrexoneNaltrexone

66--month RDBPCT, 180 mg, and 360 mgmonth RDBPCT, 180 mg, and 360 mgBRENDA every 2 weeksBRENDA every 2 weeks92% abstinent for at least a week92% abstinent for at least a week43% abstinence goal43% abstinence goalRESULTS, 360 mg compared with placeboRESULTS, 360 mg compared with placebo

25% greater decrease in heavy drinking days25% greater decrease in heavy drinking daysMedian 3 vs. 6 heavy drinking daysMedian 3 vs. 6 heavy drinking days

Small subset abstinent @ baseline (n=36), 80% reductionSmall subset abstinent @ baseline (n=36), 80% reduction41% vs. 17% complete abstinence, not stat. sig. 41% vs. 17% complete abstinence, not stat. sig.

Presenter

Presentation Notes

Naltrexone has modest efficacy for treating alcohol dependence. So why focus on a single clinical trial of naltrexone? This trial was well done: it employed advanced statistical techniques and had excellent external validity, enrolling 70% of the eligible population and not requiring abstinence for study entry. The study found efficacy for a novel injectable preparation that may have adherence advantages over oral tablets. How do we interpret the results? The higher dose of extended-release naltrexone combined with psychosocial therapy was associated with a 25% greater decrease in heavy drinking than was the combination of placebo and psychosocial therapy. Although the relative effects are of interest, absolute numbers (as displayed in Figure 3 of the original article, for example) are of greater interest. This figure suggests (by rough inspection) that after treatment, the 380-mg naltrexone group drank heavily on a median of about 3 days per month compared with about 6 days per month for the placebo group. In a subgroup analysis, naltrexone had a more impressive effect in those with a week of abstinence prior to study entry—the 190-mg and 380-mg subgroups, however, had only 17 patients each. In another subgroup analysis, the drug had efficacy in men but not women. Subgroup analyses such as these should be interpreted with caution. My take is that extended-release naltrexone has efficacy, but that future research with this drug should address improving outcomes in women and in those who do not initially establish abstinence. A more significant consideration is whether the drinking decreases were clinically important. Clearly, on each additional heavy drinking day, people are at risk for acute adverse consequences, and over time, the more heavy drinking days, the more negative health consequences. So the effects are likely meaningful, though trials that look at health outcomes beyond surrogate measures (consumption) would certainly be welcome. Unlike most other chronic diseases, alcohol dependence is characterized by loss of control and impaired motivation, which make adherence to treatment particularly difficult. Does the new injectable preparation represent an advance over oral naltrexone? A monthly injection might be easier to adhere to than a daily pill, but this is not yet known to be the case in alcohol dependence. Many people may prefer pills to avoid injections and/or the office visits to receive them. And it will be a challenge for the healthcare system to get these injections to where people with alcohol dependence can receive them from qualified personnel. So the adherence advantages remain to be seen. The niche for injectable extended-release naltrexone also remains to be seen. It will likely make sense for those who prefer it or find it easier to adhere to. But for most people with alcohol dependence, the key issue is not which preparation of a medication they choose. The issue for them is getting as many known efficacious therapies as possible: pharmacotherapy (eg, naltrexone or acamprosate), psychosocial therapy including support for treatment adherence, and mutual help. BRENDA (Biopsychosocial, Report, Empathy, Needs, Direct advice, and Assessment)

Main contraindication: opiates, pregnancyMain side effects: nausea, dizziness

Prescribing Naltrexone

Naltrexone 12.5 mg/d-->25 mg/d-->50 mg/d or 380 mg IM per month (VIP3 program)

Naltrexone 12.5 mg/d-->25 mg/d-->50 mg/d or 380 mg IM per month (VIP3 program)

Presenter

Presentation Notes

Naltrexone can be started at 12.5 or 25 mg a day and advanced to 50 mg a day. Its main contraindication is opiate dependence or need for opioids. The main side effects are nausea and dizziness, which can be avoided by starting at a low dose and increasing it to the therapeutic dose of 50 mg per day over time as tolerated, usually after a few days. Liver enzymes should be monitored because of hepatitis seen at much higher than the doses recommended for alcoholism (for example, >300 mg a day). The main difficulty with the use of naltrexone is that it can complicate pain management, leading to a need to give very high dose opioids in the event of acute pain, or stopping and restarting therapy perioperatively. What is VIP3?�VIP3, VIVITROL Information for Patients, Physicians, and Providers, is a confidential service, designed to comply with federal privacy regulations, that offers the following: �Enrollment of patients and physicians in the VIP3 program Identification and coordination of healthcare providers for injections Coordination of product delivery Adherence services Reimbursement support services Patient Assistance Program

Drugs Under Study

TopiramateOndansetronCombinationsFor people with alcohol problems, but not dependence

Targeted use

Presenter

Presentation Notes

Other medications have been studied and initial studies have shown efficacy for injectable naltrexone, topiramate, and ondansetron, at least for some patients. Combinations of effective medications are also being studied to see if they will be more effective than a single drug alone. Another related use of medications with efficacy for alcohol dependence is treatment of patients with alcohol problems but not dependence. In that circumstance use has been targeted, taking the medication just before exposure to situations in which people are predictably at risk for heavy drinking.

TopiramateTopiramate, n=371, RCT, n=371, RCT

In analyses that considered all dropouts as having relapsed to In analyses that considered all dropouts as having relapsed to baseline measures, topiramate recipientsbaseline measures, topiramate recipients……

Had greater reductions in the percentage of drinking days (from Had greater reductions in the percentage of drinking days (from a mean a mean of 82% in both groups to of 82% in both groups to 44%44% among among topiramatetopiramate recipients, compared recipients, compared with with 52%52% for placebo recipients),for placebo recipients),

Had greater reductions in liver enzymesHad greater reductions in liver enzymes

Had greater increases in abstinent days (from a mean among Had greater increases in abstinent days (from a mean among topiramatetopiramaterecipients of 10% to recipients of 10% to 38%38% compared with 9% to compared with 9% to 29%29% for placebo for placebo recipients)recipients)

Achieved Achieved ≥≥28 days of both continuous abstinence and continuous non28 days of both continuous abstinence and continuous non--heavy drinking heavy drinking soonersooner than did placebo recipientsthan did placebo recipients

Johnson BA, et al. Johnson BA, et al. JAMA.JAMA.

2007;298(14):16412007;298(14):1641––1651.1651.

The COMBINE StudyThe COMBINE Study

1616--week randomized, multiweek randomized, multi--center trialcenter trial1383 men and women with alcohol dependence1383 men and women with alcohol dependence9 arms9 arms

Naltrexone, acamprosate, both (v. placebo)Naltrexone, acamprosate, both (v. placebo)Combined behavioral intervention (CBI)Combined behavioral intervention (CBI)Medical management (all but CBI only [no pills] arm)Medical management (all but CBI only [no pills] arm)

up to 9 visits focused on medication side effects and reinforcinup to 9 visits focused on medication side effects and reinforcing g abstinenceabstinence

Anton RF et al. Anton RF et al. JAMAJAMA 2006 May 3;295:20032006 May 3;295:2003--17 (NCT00006206)17 (NCT00006206)

Presenter

Presentation Notes

A few weeks ago the COMBINE study published its results in JAMA. I was on the DSMB for this study, an experience I’d recommend if you have a similar opportunity, and Dom Ciraulo, Chair of Psychiatry was one of the site Principal Investigators and authors. This was a 16-week randomized multi-center trial that enrolled 1383 men and women with alcohol dependence. It was a complicated design with 9 arms comparing the medications naltrexone, acamprosate and both versus placebo; a specialized combined behavioral intervention; and medical management. Everyone got medical management except one of the 9 arms that received CBI only. Medical management was basically a clinician asking about medication side effects and adherence, and encouraging abstinence, during up to 9 visits. MM delivered by docs, PA, RNs, pharmacists


Good Clinical OutcomeGood Clinical Outcome%%

Medical Management and Medical Management and PlaceboPlacebo 5858Medical Management and Medical Management and Placebo and Placebo and CBICBI 7171Medical Management and Medical Management and NaltrexoneNaltrexone 7474CBI=Combined Behavioral InterventionCBI=Combined Behavioral InterventionGood Clinical Outcome=Abstinence or drinking moderate amountsGood Clinical Outcome=Abstinence or drinking moderate amountswithout problems. P<0.025 (interaction pwithout problems. P<0.025 (interaction p--value 0.02)value 0.02)

Presenter

Presentation Notes

We don’t have time to discuss all of the study results, but I’ll focus on one. Good Clinical Outcome was abstinence or drinking moderate amounts without alcohol-related problems. This good outcome was achieved significantly more often in the groups that received Medical management, placebo pills and specialized counseling CBI, or Medical management and NTX pills without specialty counseling, than it was in those who got only Medical management (and placebo pills, and no NTX or CBI). Effects of medication are modest, though, likely due to the many receptors involved in alcohol dependence that are not affected by any one medication, and other environmental factors. I am not showing the results related to acamprosate. It was ineffective in this study though other studies led to its FDA approval. No clear advantage of CBI plus NTX (on PDA) PDA CBI Alone (no pills)67 CBI and Medical Management (placebo)80 Medical Management (placebo)74 During treatment, compared with those receiving placebo alone, those receiving naltrexone, therapy or both had higher percent days abstinent (81%, 79%, 77%, respectively) vs. those receiving placebo alone (75%). During treatment, CBI alone associated with worst outcomes Acamprosate was not effective

Presenter

Presentation Notes

One message for us is that a medication, naltrexone, given with medical management, is a reasonably effective option for people with alcohol dependence. And Medical Management is something that could be done by internists accustomed to managing other chronic conditions with medications that require monitoring and adjustment. It’s as simple as a progress note like this one that prompts checking on alcohol use, queries about medication side effects and adherence, and any changes in plans. The NIAAA guide I mentioned earlier has a one page guide on using medications to treat alcohol dependence.


One year after treatment ended, the groups did One year after treatment ended, the groups did not differ significantly on drinking outcomesnot differ significantly on drinking outcomes

Alcohol dependence is an illness that, like other Alcohol dependence is an illness that, like other chronic diseases, requires ongoing care chronic diseases, requires ongoing care

Presenter

Presentation Notes

Despite that short term efficacy though, one year after treatment ended, the groups didn’t differ significantly on drinking outcomes. This is not surprising since alcohol dependence is an illness that like other chronic diseases requires ongoing care.

Oslin

DW et al. Neuropsychopharmacology. 2003;28:1546Oslin

DW et al. Neuropsychopharmacology. 2003;28:1546

Pharmacogenomics

Presenter

Presentation Notes

Given the modest effects demonstrated in clinical trials, pharmacotherapies are clearly not cures for alcohol dependence. But it may be possible to better target their use to patients for whom they are more effective. This study examined the association between two specific polymorphisms of the gene encoding the mu-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. In these data combined from 3 randomized trials, time to first relapse in the naltrexone-treated subjects was significantly longer in those with the Asp40 allele coding for the mu-opioid receptor. There were no differences between those assigned to placebo and those without the Asp 40 allele assigned to naltrexone.

Copyright restrictions may apply.

Anton, R. F. et al. Arch Gen Psychiatry 2008;65:135-144.

Good clinical outcome based on OPRM1 and medication group in thosereceiving medical management alone (no combined behavioral intervention)(test of genotype x medication interaction, P = .005)

Presenter

Presentation Notes

The asparagine-to-aspartate amino acid substitution at position 40 is caused by an A118G single nucleotide substitution, leading to structural variation in the receptor extracellular domain. This substitution has been reported to increase binding of β-endorphin and increase functional activity in vitro.20 In addition, early reports have suggested that the 15% to 25% of humans22-23 who carry the Asp40 allele show a greater response to alcohol,24-25 greater endocrine response to opioid antagonists,26 and less response to painful stimuli.27 In addition, a similar polymorphism has been reported to reduce alcohol-induced stimulation and alcohol consumption in nonhuman primates.28 However, as reported when this polymorphism was first described,19 a meta-analysis of human population studies suggested that this OPRM1 polymorphism is not associated with a higher genetic risk of developing alcohol dependence.23

Medications and Psychosocial Therapy

Usually medications given along with psychosocial therapyNaltrexone & 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 was effective in treating alcohol dependence

Presenter

Presentation Notes

In most studies medications are given along with psychosocial therapy. But questions remain regarding the minimum therapy required. For example, O’Malley and colleagues compared counseling designed to be feasible in primary medical care settings with standard cognitive behavioral therapy in clinical trials of naltrexone. Both types of counseling yielded comparable results during the initial 10 weeks of treatment and results favored primary care management after that. In another clinical trial, naltrexone was efficacious even without psychosocial therapy. Second bullet: O’Malley SS et al. Arch Int Med 2003;163:1695-1704 Third bullet: Latt NC, et al. Medical Journal of Australia 2002;176:530-534

Pharmacotherapy for Mood and Anxiety Disorders

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 and disorders can decrease alcohol use

•

Anxiety: buspirone•

Depression: fluoxetine

Nunes & Levin. JAMA 2004;291:1887Garbutt JC et al. JAMA 1999;281:1318

Nunes & Levin. JAMA 2004;291:1887Garbutt JC et al. JAMA 1999;281:1318

Presenter

Presentation Notes

About 50% of people with alcohol dependence have psychiatric comorbidity. Although selective serotonin reuptake inhibitors (SSRIs) have been efficacious for treating alcohol dependence even in patients without depression or anxiety, there is insufficient evidence to suggest their use in patients without these disorders. In people with coexisitng anxiety, buspirone can decrease heavy drinking, and in depression, fluoxetine can decrease heavy drinking. But the most important issue is to not delay treatment for psychiatric comorbidity while awaiting resolution of drinking.

Pharmacotherapy SummaryPharmacotherapy Summary

Pharmacotherapy for alcohol dependence Pharmacotherapy for alcohol dependence has efficacy and should be considered for has efficacy and should be considered for all patients with alcohol dependenceall patients with alcohol dependencePharmacotherapy has proven efficacy Pharmacotherapy has proven efficacy when prescribed along with psychosocial counselingwhen prescribed along with psychosocial counselingThere is no clear drug of choice for There is no clear drug of choice for this indicationthis indicationCombinations of efficacious drugs and Combinations of efficacious drugs and new drugs for this indication hold promisenew drugs for this indication hold promise

Presenter

Presentation Notes

In summary, pharmacotherapy for alcohol dependence has efficacy and should be considered for all patients with alcohol dependence. Pharmacotherapy has proven efficacy when prescribed along with psychosocial counseling. There is no clear single drug of choice for this indication, and combinations of efficacious drugs and new drugs for this indication hold promise.

Treatment

At one year, 2/3rds of patients have a reduction in

alcohol consequences (injury, unemployment)consumption (by 50%)

1/3rd are abstinent or drinking moderately without consequencesMonetary benefits of alcohol and drug treatment to society outweigh costs 4 to 12-fold (depending on drug and treatment type)

Miller WR et al. J Stud Alcohol 2001;62:211-20, Anon. Journal of Studies on Alcohol 1997;58:7-29, O'Brien CP, McLellan AT. Lancet 1996;347:237-240.

SummaryRecognize intoxication, consider differentialManage withdrawal according to the evidenceBrief intervention—to decrease use, maybe consequences, and link with treatmentMonitor, assess and prevent relapse

In primary careReferral for therapyPharmacotherapyAA or similar mutual help groups

JAMA February 2, 2005 Dresden Prayer Book

The Temperate and the Intemperate

Presenter

Presentation Notes

Master of the Dresden Prayer Book (fl c 1465-1515), The Temperate and the Intemperate, 1475-1480, Flemish. Tempera colors and ink on parchment. 17.5 x 19.4 cm. Courtesy of The J. Paul Getty Museum (http://www.getty.edu), Los Angeles, Calif. illustrations for a French translation of a work written by the first-century Roman historian Valerius Maximus and dedicated to the Emperor Tiberius. Written about 30 AD, the original nine volumes by Valerius recount the memorable deeds and sayings of famous Romans. Anecdotes from the lives of heroes are held up for inspiration and emulation. Behaviors such as drunkenness are condemned. During the Middle Ages the work was widely used as a handbook for rhetoric, a kind of "McGuffey's Reader" that taught morals and reading in a single passage. The illuminated page from this work known as The Temperate and the Intemperate (cover) is part of a French translation of Valerius' work made for the Cistercian Abbey near Bruges. It is, paradoxically, a "large" miniature, some seven by eight inches, and is painted on parchment in bright tempera colors and ink. In the foreground a group of happy revelers, in various stages of sobriety, carouse; while in the background a more sedate group soberly contemplates a fish on a platter. An emperor (Tiberius) and a sage (Valerius) converse at the left; beyond what is apparently an open portico, blue skies and calm streams beckon.

management of alcohol withdrawal and dependence: … of unhealthy management of unhealthy alcohol...

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