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John A. Renner, Jr., MD Consultant, Department of Psychiatry Massachusetts General HospitalProfessor of Psychiatry Boston University School of Medicine

Treatment of Addictive DisordersAlcohol and Opiates

October 22, 2017

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I have the following relevant financial relationship with a commercial interest to

disclose:

Johnson & Johnson: stockholderGeneral Electric: stockholder

Disclosures

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• Alcohol Use Disorder– Drinking Trends– SBIRT & Screening for Alcohol Related Problems– DSM-5– Alcohol Biomarkers– Alcohol Withdrawal Medications – Anticraving Medications

• Opiate Use Disorder– Changes in Abuse Patterns– Treating Opioid Overdose– Opioid Withdrawal Protocols– Opioid Agonist Therapy– Opioid Antagonist Therapy

• Appendix – Managing Dual Diagnosis Patients

Agenda

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Alcohol Use; Monitoring The Future, 1974 - 2016

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Alcohol Use DisordersEpidemiology:

•Alcohol use accounts for 1 in 10 deaths in US adults age 20 to 64, approximately 88,000 deaths per year

•Drinkers lives are shortened by about 30 years

•Drinking costs US $224 billion a year due to lost productivity, including reduced wages and health care costs

CDC 2014 http://www.cdc.gov/alcohol/index.htm

http://www.cdc.gov/alcohol/index.htm

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SBIRT & SCREENING FOR PROBLEM DRINKING

Screening, Brief Intervention, Referral to Treatment (SBIRT):

Single Alcohol Screening Question (SASQ)“How many times in the past year have you had 5 or more

drinks in one day?” (4 drinks for women)Any positive response within the past year warrants

assessment for problem drinking. Review drinking during the last 28 days. Review DSM-5 criteria.

(Canagasby & Vinson, Alcohol Alcohol, May-June 2005)www.niaaa.nih.gov/guide

A large British study has questioned the effectiveness of screening and brief interventions in primary care settings

E Kaner, et al. BMJ 2013;346:e8501

http://www.niaaa.nih.gov/guide

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• The SBIRT approach is effective for individuals with heavy/at risk drinking

• There is little evidence of efficacy for individuals with an alcohol use disorder or a drug use disorder

• More intensive counseling or interventions are required for individuals with more serious problems

• None the less all patients should be screened to identify risky or problem drinking

R.Saitz JAMA 2014;312(5):502-513

RECOMMENDATIONS FOR SCREENING

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DSM-5 CHANGESCRITERIA FOR SUBSTANCE USE DISORDERS

1. USE IN LARGER AMOUNTS / LONGER PERIODS THAN INTENDED2. UNSUCCESSFUL EFFORTS TO CUT DOWN 3. EXCESSIVE TIME SPENT TAKING DRUG4. FAILURE TO FULFILL MAJOR OBLIGATIONS5. CONTINUED USE DESPITE KNOWLEDGE OF PROBLEMS6. IMPORTANT ACTIVITIES GIVEN UP7. RECURRENT USE IN PHYSICALLY HAZARDOUS SITUATIONS8. CONTINUED USE DESPITE SOCIAL OR INTERPERSONAL PROBLEMS 9. TOLERANCE10. WITHDRAWAL11. CRAVING

SEVERITY:0 TO 1 CRITERIA: NO DIAGNOSIS2 TO 3 CRITERIA: MILD4 TO 5 CRITERIA: MODERATE6 OR MORE CRITERIA: SEVERE

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ALCOHOL BIOMAKERS

INDIRECT TESTS – all measure long-term drinking only

1. Carbohydrate-Deficient Transferrin (CDT): most sensitive indicator of relapse (serum) > 20 units/L in men > 26 units/L in women

2. GGT: > 65 units/L in men > 50 units/L in women

3. MCV> 95 microns/cubic ml. in males > 100 microns/cubic ml. in females

4. LFT’s: AST, ALT, & Alk. Phos.

5. CAMP in WBC are 3 x normal

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ALCOHOL BIOMARKERS

DIRECT TESTS – can detect recent relapse / drinking

1. Blood Alcohol Concentration (BAC)

2. Ethyl Glucuronide (EtG) is present for 5 days in urine, very sensitive and may have a high incidence of false positives. Use can be problematic in monitoring situations.

3. Phosphatidyl Ethanol (Peth): 2 drinks/day for 2 weeks (in RBCs) will track moderate drinking; is positive for 2-4 weeks

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ALCOHOL SUBTYPESNESARC study, adapted from Moss H, Drug Alc Depend, 2007

YOUNG ADULTS32%

LATE ONSET38%

EARLY ONSET30%

EPISODIC HEAVY BINGE DRINKING

MODERATE DRINKING SEVERE CHRONIC DRINKING

LITTLE PSYCHO-PATHOLOGY

MINIMAL PSYCHO-PATHOLOGY

SEVERE PSYCHO-PATHOLOGY

MINIMAL GENETIC RISK MODERATE GENETIC RISK SEVERE GENETIC RISK

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NEUROBIOLOGY OF ALCOHOL:CHRONIC ALCOHOL USE

• UP-REGULATION OF NMDA RECEPTORS: EXCITATORY NEUROTRANSMISSION, PRIMARY CAUSE OF WITHDRAWAL SYMTPOMS

• DOWN-REGULATION OF INHIBITORY GABARECEPTORS

• DOWN-REGULATION OF EXCITATORY DOPAMINE D-2RECEPTORS

• INCREASED NOREPINEPHRINE ACTIVITY

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NEUROBIOLOGY OF ALCOHOL

EFFECTS OF ALCOHOL WITHDRAWAL:• CNS HYPERACTIVITY- NO OPPOSITION TO

ALCOHOL INDUCED EXCITATORY STATE(NMDA HYPERACTIVITY)

• RELEASE OF CRF

PREDICTORS OF RELAPSE:• DELAYED RECOVERY OF D-2 RECEPTOR

SENSITIVITY AFTER DETOX • ELEVATED ACTIVITY IN THE VENTROMEDIAL

PREFRONTAL CORTEX (vmPFC)

R. Sinha, JAMA Psychiatry 2013

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MEDICATIONS FOR ALCOHOL WITHDRAWAL

• Benzodiazepines remain the standard of care

• Anticonvulsants (carbamazine & valproic acid) are effective but have significant side effects (Myrick, 2003)

• Gabapentin may offer an alternative option for ambulatory withdrawal treatment:• 400 mg TID for 8-10 days• Effective control of withdrawal• As compared to lorazepam, less craving,

anxiety & sedation• Reduced probability of relapse in post-

withdrawal week (Myrick, Alcohol Clin Exp Res, 2009 33:1582-88)

• Can present abuse problems in some patients

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RELAPSE PREVENTION PHARMACOTHERAPY

ANTICRAVING MEDICATIONSAS

THE NEW STANDARD OF CARE

Consider, immediately post-detoxification for ALLalcoholics

Efficacy requires counseling and/or frequent physician monitoring; med compliance is critical for success

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• DISULFIRAM *• NALTREXONE (PO* & IM* formulations)• ACAMPROSATE *• TOPIRAMATE• ONDANSETRON• SSRIs• CLOZAPINE• QUETIAPINE

* FDA APPROVED

ADDICTION PHARMACOTHERAPY:MEDICATIONS IN THE LONG-TERM MANAGEMENT OF ALCOHOLISM

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NALTREXONE (ReVia)

Opioid antagonist / oral formulation• Modulates the mesolimbic dopamine system in the VTA &

projections to the nucleus accumbens• Reduces alcohol craving and euphoric effects of alcohol• Dose: 50 to 100 MG QDaily with meals• Side effects

– GI: abdominal pain, decreased appetite, nausea– Sedation: daytime sleepiness, fatigue, insomnia, headache

• Works best with compliant patients(Zweben, 2008); requires counseling (CBT) or frequent MD monitoring visits (Project Combine, 2006)

• Efficacy questioned in women (O’Malley, 2007)

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Naltrexone Outcome associated with variants of opioid receptor gene OPRM 1

Asp 40 Allel Asn 40 Allel

NALTREXONE 87%GOOD OUTCOME

55%GOOD OUTCOME

PLACEBO 49%GOOD OUTCOME

54%GOOD OUTCOME

Project Combine; Anton R. Arch Gen Psychiatry. 2008.In meta-analysis of 6 studies, patients carrying the G allele of A118G polymorphism of OPRM1 had lower relapse rates, but no difference in abstinence rates (Chamorro et al, 2012)

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ER-NALTREXONE (Vivitrol)

• Long-acting injectible formulation: 80 mg IM q 28 days• Screen LFTs• More stable plasma concentrations compared to the oral

formulation• Side effects: NAUSEA & HEADACHE; more sedation than with

the oral formulation• Injection site reactions possible• Best results in patients sober 1 week prior to starting the

medication• Efficacy shown in more severe alcoholics

– Reduction in heavy-drinking days (48.9% vs 30.9% on placebo)

– Pettinati HM, Alcohol Clin Exp Res, May 2011

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RECOMMENDATIONS FOR USE OF NALTREXONE

• Screening tests for hepatic function• Begin 50 mg ORAL Naltrexone after 4-5 days sobriety

(post detox)• If no response after 2 weeks, go to 100 mg• If no response or minimal responses, add

Gabapentin 12OO mg/Day– Anton R. Am J Psychiatry, July 2011

• If no response, switch to ER-Naltrexone– Pettinati HM. Alcohol Clin Exp Res, May 2011

• If no response consider Acamprosate or Disulfiram

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DISULFIRAM (Antabuse)

• DOSE: 500 mg po qd x 10 days; then 250 mg po qd• SIDE EFFECTS: drowsiness, headache, metallic taste,

decreased libido/potency• SUPPORTIVE COUNSELING NECESSARY• SUPERVISED DOSING recommended• Follow serial LIVER FUNCTION TESTS

– Monitor for ALCOHOL-INDUCED HEPATITIS• Rx for Antabuse reaction: BENADRYL 50 mg IM or IV

Jergensen CH, Alcohol Clin Exp Res, Oct 2011

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ACAMPROSATE (Campral)

• Glutamate antagonist• Alters GABA & NMDA systems

– Restores balance between inhibitory & excitatory neurotransmission

– Attenuates acute & prolonged withdrawal– Reduces rewarding effects of alcohol

• No tolerance, withdrawal or sedation• Minimal side effects (mild diarrhea)• Excreted through the kidneys• No drug-drug interactions• Dose: 666 mg PO TID

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ACAMPROSATE (Campral)

• COCHRANE REVIEW, Rosner S, 2011– 24 RCT’s with 6915 subjects– Reduced risk of relapse to 86% of the risk in the placebo group– Increased by 3 the number of abstinent days per month– NNTB = 9– Authors anticipate better results in fully compliant patients– Post-treatment benefit (10 RCT’s) effect sustained 3 to 12 mos.

after end of treatment– ACA vs. NTX (6 trials; inconclusive data)– ACA plus NTX – results promising but inconclusive

• 41% higher dropout rate than ACA alone

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PROJECT COMBINE

1383 patients randomized to varying combinations of oral Naltrexone, Acamprosate, combined behavioral intervention (CBI) and medical management (MM)

• ALL groups improved• Naltrexone + MM had the best outcome

– Adding CBI did not improve results– Adding Acamprosate did not improve results

• One-year outcome: no significant differences among the groups

JAMA. 2006;295:2003-2017.

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TOPIRAMATE (Topamax)

• Facilitates GABA• Inhibits Glutamate • Reduced drinking and craving:

– DBPC trial (Johnson. Lancet. 2003)– 150 subjects

• Dose: 25 mg PO QD, then increase dose up to 100 mg TID over an 8 week period

• Side effects: fatigue & cognitive dulling• Replicated in 371 subjects

– DBPC randomized trial (Johnson. JAMA. 2007)• Changed to pregnancy CATEGORY D in 2011

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ONDANSETRON (Zofran)

• Anti-nausea drug approved 1991• Selective 5-HT3 blocker• Reduced drinking in EARLY-ONSET Alcoholism (Type B)

Dose: 4 microgm/kg po bid – equivalent dose not currently marketed

• DBPC 11-week trial; 321 patients– Johnson BA. JAMA. Aug 23, 2000

• Less expensive generic version available since 2008• Higher efficacy in individuals with the LL GENOTYPE of the

5-HTT gene– Johnson BA. AM J PSYCHIATRY, Jan 2011

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SSRIs May Reduce Drinking in Some Alcohol Subtypes

• CITALOPRAM: Reduced drinking in non-depressed male alcoholics; no efficacy in non-depressed female alcoholics (Naranjo, 2000)

• SERTRALINE: Reduced drinking in Late Onset men; no efficacy, or made drinking worse in Late Onset women or Early Onset men or women (Pettinati, 2004)

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QUETIAPINE (Seroquel)

• Atypicals target both DA & 5-HT Systems• Reduced substance use on clozapine• 12-week DBPC trial in 61 subjects• 11 of 61 achieved total abstinence:

– 9 were on quetiapine– 2 were on placebo

• TYPE B/Early Onset – marked quetiapine benefit• TYPE A/Late Onset – no difference from placebo

Kampman & Pettinati. J Clin Psychopharmacology. 2007

A large meta-analysis of 13 DB studies of antipsychotics failed to demonstrate efficacy for relapse prevention. Subjects were not categorized by subtypes. T. Kishi, J Clin Psych 2013

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ALCOHOLISM PHARMACOTHERAPY SUGGESTIONS

ALCOHOLISM SUBTYPE INTERVENTIONBinge Drinking Young Adults Education

Motivational Enhancement TherapyNaltrexone - oral

Early Onset; SeverePsychiatric Co-morbidity

OndansetronTopiramate; Atypical Antipsychotics ?

Late Onset; Moderate Naltrexone – ER formulationTopiramateSSRIs in males

Late Onset; SeverePsychiatric Co-morbidity

Naltrexone – ER formulationTopiramate

Elderly Onset Naltrexone – ER formulation

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Marijuana as a Medication for Alcoholism?

• Among other purported benefits of marijuana, it has been recommended as a substitute for alcohol in some alcohol-dependence individuals

• A review of the literature concluded that there is no clear pattern of outcomes related to marijuana substitution. Any clinical recommendations were thought to be premature.

Subbaraman MS, Alcohol Alcohol 2014, 49(3):292-298

• People using both marijuana and alcohol reported increased alcohol consumption and greater prescription drug misuse (Osilla et al, 2014)

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Treatment Costs Alcohol Dependent Patients

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Patient Management Techniques

• SOBRIETY is the primary goal• Supportive care - BUILD DEFENSES• MEDICATIONS for relapse; monitor compliance• Treat co-morbid psychiatric disorders• Learn to work with A.A.• CBT & relapse prevention counseling• Anticipate lapses & relapses• Active therapeutic stance• For persistent insomnia: TRAZODONE• Avoid prescription tranquilizers

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Substances for Which Most Recent Treatment Was Received in the Past Year among Persons

Aged 12 or Older: 2012

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Heroin Use; Monitoring The Future, 1974- 2016

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Narcotics use other than heroin, Monitoring the Future 1974 - 2016

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National Survey of Drug Use and Health 2014, SAMHSA

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CDC3/18/17

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National Survey of Drug Use and Health 2014, SAMHSA

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The Treatment of Opioid Overdose

• Signs: Coma, pinpoint pupils, depressed pulse and respirations, hypothermia

• Treatment– Naloxone (Narcan) 0.4 mg (1ml) iv, q.4 min., prn– If no response, treat for sedative/hypnotic OD– Monitor methadone overdose patients for 24- 48 hrs.– Single naloxone dose lasts 1-4 hours– Fentanyl may require multiple doses of naloxone to

reverse

Major public health initiative with Naloxone Rescue formulations; new standard of care

www.mghcme.org*Data compiled from San Francisco Medical Examiner’s Reports, www.sfgsa.org**no data available for FY 2000-2001

0

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begins, 2003

Heroin-related Deaths, San Francisco: 1993-201047

Introduction of intranasal naloxone

http://www.sfgsa.org/Chart1

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1993-19941994-19951995-19961996-19971997-19981998-19991999-20002002-20032003-20042004-20052005-20062006-20072007-20082008-20092009-2010

Heroin-related deaths118119155108130130121785941581872510

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Neurobiology of Opioid Withdrawal

• Hyperactivity of nor-adrenergic neurons in the locus coeruleus causes:

– Increased BP, HR, respirations– Increased sweating, diarrhea–Clonidine & opiates reverse these effects

• Increased GABA effects; reduced dopamine in the nucleus accumbens cause:

–Dysphoria, depression, craving–Only opiates (methadone & buprenorphine)

reverse these effects

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Withdrawal Treatment - Methadone

• Initiate treatment only after documenting withdrawal• Do not exceed initial dose of 20 mg methadone (10 mg in

younger addicts)• May repeat dose in 2 hrs., if withdrawal increases • Inpatients rarely require over 40 mg / 24 hours• Titrate dose to avoid intoxication or withdrawal• Detox taper:

– cut by 10 mg / day down to 20 mg– then cut by 5 mg / day down to zero

• Adding Very Low Dose Naltrexone (0.125 or 0.250 mg q daily) may improve outcome and ease transition to post-detox care (Mannelli, Am J Addict 2009)

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Inpatient Buprenorphine Withdrawal Rx

• Document withdrawal before giving 1ST dose• DAY 1: BUP/NALOXONE 4/1 mg SL, may redose in 2 to

4 hrs, up to 8/2 mg SL• DAY 2: 8/2 to 12/3 mg SL• DAY 3: 6/1.5 mg SL, final dose; may also taper 2-3

days• 7 day protocol may be more effective• Addicts prefer buprenorphine over methadone or

clonidineUmbricht, 2003

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Withdrawal Rx - Outcome Data Percent patients drug-free at 13 weeks,

MEDICATION INPATIENTDETOXIFICATION

OUTPATIENTDETOXIFICATION

BUPRENORPHINE / NALOXONE

77 % 29 %

CLONIDINE 22 % 5 %

W. Ling, 2005

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Opioid Agonist Therapy BUPRENORPHINE:• High affinity partial MU-opioid agonist / “ceiling effect” for

respiratory depression– Low overdose risk

• Kappa receptor antagonist• Sublingual buprenorphine/naloxone tablet

– New film strip formulation in 2010– Generic sublingual formulations 2013

• Extended release subdermal rods 2016• Over 400,000 patients currently in active treatment• Prescribing requires training & CSAT / DEA WAIVER waiver

limit can be increased from 30 to 100 to 275

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Opioid Agonist Therapy

BUPRENORPHINE:• DSM-5 criteria for addiction (Opioid Use Disorder–Moderate)• Can treat patients age 16 and older• Rapid stabilization in 1-2 days• Maintenance range: 12-24 mg• Long half-life: 24 to 72 hr dosing• No evidence of hepatoxicity (Bogneschutz, 2010)• Best option for younger, motivated patients with shorter

addiction histories and less sociopathy• Not recommended in severe chronic pain syndromes

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Opioid Agonist Therapy

BUPRENORPHINE – OUTPATIENT INDUCTION RECOMMENDATIONS:

• Abstinence prior to first BUP/NX dose:– 16 hrs for short-acting opioids (heroin)– 24 hrs for sustained-release opioid medications– 36 hrs for methadone (30mg x 2 weeks; 15mg x 1 day;

no methadone x 1 day; then induce on BUP/NX)• COWS score 8-10 before 1st dose (2 or 4 mg)• Rapid escalation to 16mg, if needed, by end of day 1

Gunderson EW, et al. Am J Addiction Sept, 2011

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The Role of Counseling

• Standard recommendations since 1965 have stressed the importance of ancillary counseling for success in opioid agonist therapy

• Benefits are well documented by research –Ball & Ross, 1991; McLellan,1993

• Four recent buprenorphine trials suggest that brief, frequent physician medication monitoring visits are equal to, if not more effective than more intensive drug counseling –Fiellin, 2006; Weiss, 2011

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BUPRENORPHINE IN PREGNANCY

The MOTHER Study:• 175 pregnant opioid dependent women• 8 international sites• DB, double-dummy, flexible-dosing, randomized, controlled

trial (methadone PO vs. buprenorphine SQ)• Both drugs safe and effective• Retention: 72% methadone vs. 67% buprenorphine*

– * Most BUP dropouts in first few days, or with first dose

• Comparison of 131 neonates (BUP vs. Methadone)– Morphine dose required for NAS: 1.1 vs. 10.4 mg

morphine– Duration NAS: 4.1 vs. 9.9 days– Duration hospital stay: 10.0 vs. 17.5 days

Jones HE, et al. N Eng J Med, Dec 2010

www.mghcme.orgJones et al, N Engl J Med, 2010

Neonatal Abstinence Syndrome

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Buprenorphine

Recommendations for minimizing diversion & abuse:• Use BUP/NX for all patients except pregnant women• Whenever possible keep dose to 16/4 mgs or below• After initial stabilization, wait at least 5-7 days to assess benefit of

any dose increase• Over 16/4 mg, emphasize psychosocial techniques to manage

ongoing craving or use• Weekly physician visits until stable• Regular urine toxicology screens• Regular check of state Prescription Drug Monitoring Program• Call-backs for pill counts and tox screens, as needed• Dose reductions to 8/2 mg for long-term patients• Encourage AA / NA

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Opiate Agonist Therapy – Pain Management

• Opioid agonist maintained patients do experience pain and will have high tolerance to opioids

– Manage with non-opioids meds if possible• For Methadone patients

– a full opioid agonist can be added as needed, or dispense methadone in divided doses

• For Buprenorphine patients– add supplemental BUP dose or dispense in divided doses– or add full agonists to daily buprenorphine dose– switch to methadone or morphine

• For patients with chronic pain and addiction– Buprenorphine/Naloxone in divided doses may be ideal

for long term management

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COMPARING METHADONE & BUPRENORPHINE / NX

BUP/NX METHADONESetting Office-based Clinic-basedDiagnosis DSM-5 1 year proven historyAge > 16 > 18 Target dose 12 to 16 mg 80 to 120 mgSafety (risk of OD) Ceiling effect No ceiling effectCardiac risks None Over 100 mg, QTc riskPregnancy Safe; less NAS SafeEfficacy Comparable in multiple studiesPain treatment Off-label FDA approved

Diversion risk Higher Low from clinics

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NEW PHARMACOTHERAPIES

• Lofexidine for opioid withdrawal treatment – comparable to clonidine but fewer side effects and better efficacy. Has not yet been approved by FDA

• Probuphine - extended release subdermal buprenorphine implant rods. (R. Rosenthal, W. Ling, et al. Addiction 8/2013)• FDA approved 2016. • Patients must be stabilized 1st on BUP/NX SL, 8mg/2mg or a

lower dose• Patients may require supplemental SL BUP/NX• Improved medication compliance• Option for stable long term patients; not appropriate for

patients new to treatment or unstable patients• Monthly injectable buprenorphine / NDA submitted

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Opioid Antagonist Therapy ER-NALTREXONE (Vivitrol)• Long-acting injectable formulation

– 380 mg IM every 28 days• FDA approved for opioid use disorder in 2010• Questions:

– 24 week placebo controlled trial in Russia– 250 patients in randomized control design– FDA approval prior to publication

Krupitsky E, Lancet, April, 2011• Many positive clinical reports, but no well designed

studies comparing ER-NX to Methadone or to BUP/NX. NIDA trial of BUP/NX vs ER-NX is in final stages.

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Opioid Antagonist Therapy

ER-NALTREXONE (Vivitrol) – Clinical Concerns• Identification of appropriate patients• Difficulty initiating treatment – risk of precipitated opioid

withdrawal; patients must be opioid free for 3 days from short-acting opiates; 7 days from long-acting opioids

• Risk for accidental overdoses and death:– Opioid use at end of 1 month dosing interval– Opioid use after missing monthly injection– Attempts to overcome opioid blockade

• Contraindicated in acute hepatitis / liver failure• Lack of long-term studies• Managing need for acute analgesia has not been a problem;

Naltrexone blockade can be over-ridden in inpatient settings

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Treatment Costs Opiate Dependent Patients

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Cost Containment Issues

• State efforts to limit funding for treatment of opioid use disorder• Illinois has limited BUP/NX Medicare coverage to 1 year• Ohio and other states have proposed dose limit of 16/4 mg BUP/NX• Pending budget tsunami for new Hep C drugs: sofosbuvir (Solvaldi)

from Gilead Sciences– $1000 per pill or $84,000 to $100,000 for 12 week course of treatment

($ 2.27 Billion sales 1st quarter 2014)– 90% efficacy– 3 million US infected; 50% in public sector (Veterans Administration,

Medicare, prison population) primarily IV drug users– States fear out of control costs

• Buprenorphine plus counseling reduced total health care costs compared to untreated individuals (Lynch FL, Addiction Science & Clinical Practice 2014, 9:16)

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john.renner@va.gov

Questions ?

mailto:john.renner@va.gov

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Alcoholism: Rank of Co-morbid Conditions

1. Abuse of a second substance

2. Antisocial personality disorder

3. Phobias (& other anxiety disorders)

4. Major depressive disorder:13% of women alcoholics3% of male alcoholics

5. Dysthymic disorderNOTE: Co-Morbidity is the norm for most

alcoholics seen in any clinical setting

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Depression in Alcoholics• 20% of SUD patients have a co-occurring mood or anxiety disorder

(NESARC, 2004)

• Prolonged dysphoria & depression - rule out substance-induced depression

• For alcoholics with an independent major depressive disorder or dysthymic disorder. Review of randomized, DBPC trials, 1980 to 2009:– Efficacy shown for tricyclics and nefazodone– SSRI’s data currently inadequate

Iovieno N, et al. J Clin Psychiatry, August 2011

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Failure to Respond to Antidepressant Meds

• Medication NON-COMPLIANCE• Check for RELAPSE:

– CDT– GGT

• Check plasma levels of TCAs• Consider enforced therapy• Consider adding NALTREXONE or

ACAMPROSATE

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Bipolar Disorder and Co-Occurring Alcoholism

• Drinking typically follows onset of mania• Patients rarely relapse when depressed or euthymic• Alcoholism often remits after moods are stabilized• Medication SUGGESTIONS (no adequate DBPC trials):

– BIPOLAR I LITHIUM

– BIPOLAR II VALPROIC ACIDATYPICAL ANTISPYCHOTICS

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DIAGNOSIS:• Wait 4 to 6 weeks for withdrawal symptoms to clear• Positive family history• +/- Symptoms antedate alcohol use

TREATMENT RECOMMENDATIONS:• Generalized anxiety dis.: BUSPIRONE • Panic disorder: ANTIDEPRESSANTS

BEHAVIORAL THERAPY• Agoraphobia: ANTIDEPRESSANTS

BEHAVIORAL THERAPY• Social phobia: PROPRANOLOL

or CLONIDINE

Anxiety Disorders in Alcoholics

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Treating ADHD in at Risk Patients

20% to 25% incidence of ADHD with any psychoactive substance use disorder

TREATMENT PROTOCOL – Adults with SUD & co-occurring ADHD:• CBT X 2 weeks without medication• Then start meds if symptoms persist – medication choices ranked

by risk potential– Atomoxetine (Stratera) – has no abuse potential– Bupropion – Desipramine– Extended–Release Stimulants:

• Methylphenidate ER – generic (Concerta) or • Adderal XR (amphetamine/dextroamphetamine mixed salts)

T. Wilens, 2012

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Anxiety Disorders in Addicts

The Role of Benzodiazepines:• Comprehensive literature review• Efficacy demonstrated for:

GAD, panic disorder and agoraphobia• Probable efficacy for:

Social phobia, alcohol induced anxiety disorders • Little evidence of added risk for medication abuse or

increased relapse Posternak & Mueller. Am J Addict. 2001;10:48-68.

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Naloxone Rescue Formulations

Treatment of Addictive Disorders�Alcohol and Opiates �October 22, 2017DisclosuresAgendaSlide Number 4Alcohol Use DisordersSBIRT & SCREENING FOR PROBLEM DRINKING� RECOMMENDATIONS FOR SCREENINGDSM-5 CHANGES�CRITERIA FOR SUBSTANCE USE DISORDERSALCOHOL BIOMAKERSALCOHOL BIOMARKERSALCOHOL SUBTYPES�NESARC study, adapted from Moss H, Drug Alc Depend, 2007 NEUROBIOLOGY OF ALCOHOL:�CHRONIC ALCOHOL USENEUROBIOLOGY OF ALCOHOLMEDICATIONS FOR ALCOHOL WITHDRAWALRELAPSE PREVENTION PHARMACOTHERAPYSlide Number 16NALTREXONE (ReVia)Naltrexone Outcome associated with �variants of opioid receptor gene OPRM 1ER-NALTREXONE (Vivitrol)RECOMMENDATIONS FOR USE OF NALTREXONEDISULFIRAM (Antabuse)ACAMPROSATE (Campral)ACAMPROSATE (Campral)PROJECT COMBINETOPIRAMATE (Topamax)ONDANSETRON (Zofran)SSRIs May Reduce Drinking in Some Alcohol SubtypesQUETIAPINE (Seroquel)ALCOHOLISM PHARMACOTHERAPY SUGGESTIONSMarijuana as a Medication for Alcoholism?Treatment Costs Alcohol Dependent PatientsPatient Management Techniques�Substances for Which Most Recent Treatment Was Received in the Past Year among Persons Aged 12 or Older: 2012Slide Number 34Slide Number 35Slide Number 36Slide Number 37Slide Number 38Slide Number 39Slide Number 40Slide Number 41Slide Number 42Slide Number 43Slide Number 44Slide Number 45The Treatment of Opioid OverdoseSlide Number 47Neurobiology of Opioid WithdrawalWithdrawal Treatment - Methadone �Inpatient Buprenorphine Withdrawal Rx�Withdrawal Rx - Outcome Data Percent patients drug-free at 13 weeks, Opioid Agonist Therapy �Opioid Agonist Therapy �Opioid Agonist Therapy �The Role of Counseling �BUPRENORPHINE IN PREGNANCYSlide Number 57Buprenorphine �Opiate Agonist Therapy – Pain Management �COMPARING METHADONE & BUPRENORPHINE / NXNEW PHARMACOTHERAPIESOpioid Antagonist Therapy �Opioid Antagonist Therapy �Treatment Costs Opiate Dependent PatientsCost Containment IssuesQuestions ?Alcoholism: Rank of Co-morbid Conditions �Depression in Alcoholics Failure to Respond to Antidepressant Meds �Bipolar Disorder and Co-Occurring Alcoholism�Slide Number 71Treating ADHD in at Risk PatientsAnxiety Disorders in AddictsSlide Number 74