Clinical strategies in the management of Alcohol Use Disorders. Lundbeck Institute, Copenhague march 2015

Clinical strategies in the management of alcohol use

disorders Antoni Gual

Addictions Unit. Psychiatry Dept. Neurosciences Institute. Hospital Clínic de Barcelona. IDIBAPS.

tgual@clinic.cat

Conflicts of interest

Interest Name of organisation

Current roles and affiliations

Addictions Unit, Psychiatry Dept, Neurosciences Institute, Hospital Clinic, University of Barcelona; IDIBAPS; RTA; Vice President of INEBRIA, President of EUFAS

Grants Lundbeck, D&A Pharma, FP7, SANCO

Honoraria Lundbeck, D&A Pharma, Servier, Lilly, Abbvie

Advisory board/consultant

Lundbeck, D&A Pharma, Socidrogalcohol (Alcohol Clinical Guidelines) 2013

•  Who is in front of us? A humanistic approach to persons with AUD.

•  Is patient centered care needed? •  The role of assessment •  Setting goals through shared decision making •  Pharmacological treatments •  Psychosocial treatments •  Summary & Conclusions

Your opinion matters !!

•  What is the biggest challenge when managing alcohol dependent patients at the clinic?

Please, write down in a piece of paper a short answer to this question

The case of Tom

Clinical Picture

Humanistic Picture

Patient-Centered Care (PCC)

Providing care that is respectful of and responsive to individual patient preferences, needs, and values, and ensuring that patient

values guide all clinical decisions.

Institute of Medicine, 2001

“No decision about me, without me”.

Defining attributes of PCC

•  Holistic •  Individualized •  Respectful •  Empowering

Morgan and Yoder (2012)

Expected outcomes of PCC

•  Increased satisfaction with health care

•  Greater perceived quality of care

•  Increased commitment •  Better compliance •  Improved health outcomes.

Clinicians and patients should discuss: •  ambivalence toward change; •  patient goals (eg, abstinence vs decreasing drinking vs no

change); •  preference for group based or individual psychosocial treatment •  differences in the privacy and cost of the various options •  medication treatments

Clinical management

Assessment

Goal setting

Abstinence oriented Reduced drinking

AUD. Assessment dimensions. DIMENSION DIAGNOSTIC CRITERIA Drinking Quantity & Frequency

Tolerance & Withdrawal Craving

Medical harm Continued use despite medical problems Recurrent drinking (physically hazardous)

Behavioural Uncontrolled intake Unsuccessful efforts to stop Time spent around alcohol

Social harm Given up or reduced activities Use despite social or interpersonal problems Failure to fulfil major role obligations

Assessment of drinking patterns

•  Use Standard Drinks (8-10gr in EU) •  Measure in grams/week •  Ask quantity & frequency specifically •  Ask for labour & weekend days separately •  Identify binge drinking (>6 drinks pdo) •  The ‘normal day’ strategy •  Use standard tools whenever possible: AUDIT

Bio-psycho-social assessment (1)

Medical assessment (Why?)

•  Very high medical comorbidity

•  Improves adherence to treatment •  Reduces stigma

Medical assessment (How?)

•  Physical examination

•  Blood tests (GGT, VCM, ASAT, ALAT, VHC, etc)

•  Focussed Anamnesis – Accidents – A&E and hospital admissions – Alcohol-related diseases

Psychological / Psychiatric Assessment •  Alcohol related distress

–  Feeling guilty –  Irritability –  Insomnia –  Antisocial behaviour

•  Psychiatric comorbidity –  Depression –  Suicidal behaviour –  Anxiety disorders –  Personality disorders

12.20 12.20

Lifetime prevalence of psychiatric disorders and co-occurrent alcohol dependence1,2

Comorbid alcohol

dependence

Comorbid alcohol

dependence

Anxiety disorder Mood disorder

Lifetime prevalence of psychiatric disorder2

Lifetime prevalence of co-occurrent alcohol dependence and psychiatric disorder1

30% 17%

GAD Phobia PTSD

depressive disorder Bipolar

disorder

1.  Kessler et al. American Journal of Orthopsychiatry 1996; 66(1): 17-31 2.  National Comorbidity Survey Replication NCS-R. Lifetime prevalences estimates www.hcp.med.harvard.edu/ncs/index.php

Social Assessment •  Family status (divorce, ACOAs, etc) •  Work (unemployment, unstability, etc) •  Economical situation (debts, financial

problems, etc) •  Educational level (lower degree than expected,

children with low qualifications)

Bio-‐psycho-‐social assessment (3)

How to do it

•  Empathic style •  Avoid judgmental attitudes •  Stick to facts. Do not discuss why. •  Don’t ask just about alcohol. Tobacco, BZD

and illicit drugs are also relevant. •  Try to understand the story and the dilemma

behind •  Try to identify strengths of the patient

Clinical management

Assessment

Goal setting

Shared decision making

•  Helping patients better understand their medical conditions;

•  Providing information about benefits and adverse effects of treatment options;

•  Supporting patients while they clarify their values and preferences;

•  Providing support while patients implement their decisions

•  working with family and caregivers when patients have impaired decisional capacities

Elwyn et al, 2014

Help patients explore and form their personal preferences

Describe the alternatives in more detail (use decision support tools if appropriate)

Explain the need to consider alternatives as a team

This strategy fits well with an integrated care approach

Clinical management

ASSESSMENT

Goal setting

DETOXIFICATION Indicated when: •  Signs or symptoms of AW are present •  PaEent drinks above 120gr of alcohol daily Not indicated when: •  PaEent is absEnent >72h and no signs of AW are present

•  PaEent does not agree to an absEnence goal

Clinical Ins2tute Withdrawal Assessment (CIWA)

•  Nausea and vomiEng •  TacEle disturbances •  Tremor •  Auditory disturbances •  Paroxysmal sweats •  Visual disturbances •  Anxiety •  Headache, fullness in head •  AgitaEon •  OrientaEon and clouding of sensorium

BENZODIAZEPINES (BZD) •  Long half-‐life BZD are preferred: Diazepam and chlordiazepoxide are the golden standard

•  Loading dose Technique: a standard dose of the BZD is given every 2 hours unEl light sedaEon is reached.

•  Tapering technique: iniEal dose of BZD based on history. Then adjust and taper.

•  Lorazepam and oxazepam are indicated in paEents with impared liver funcEon

•  BZD should only be used short term to prevent risk of addicEon

Clinical management

ASSESSMENT

Goal setting

Timeline followback

•  Retrospective assessment of drinking behaviour.

•  Reliable and valid for a variety of populations for time frames of up to one year.

(Sobell & Sobell, 1992, 1996)

•  Avoid withdrawal signs •  Treat comorbid conditions (mental & physical) •  Accept and understand his disease •  Reduce his desire & craving for alcohol •  Reduce the priming effects of alcohol if drinking •  Promote abstinence or reduction of alcohol •  Improve coping skills •  Improve quality of life

TREATMENT: Group of therapeutic processes designed to help the patient to:

S -‐ pSychosocial H -‐ pHarmacological

Pharmacological treatments

Alcohol use Abstinence - low risk - hazardous use - harmful use -- dependence

Alcohol related problems

Recommended psychosocial

interventions Primary prevention -- B

rief interventions --

Specialized treatment

Pharmacological interventions

Alcohol use Abstinence - low risk - hazardous use - harmful use -- dependence

Alcohol related problems

Recommended psychosocial

interventions Primary prevention -- B

rief interventions --

Specialized treatment

Pharmacological interventions

Widening the scope of pharmacological treatments

•  Classical approach: Abstinence oriented (disulfiram*, acamprosate*, naltrexone*, topiramate)

•  Substitution therapy: BZD, sodyum oxibate, baclofen

•  Reduction approach: nalmefene*, naltrexone, topiramate, gabapentine.

* Registered indication

Target of Pharmacological treatments

Goal Example Decrease craving Acamprosate Decrease priming Nalmefene Decrease impulsivity Topiramate Aversive reaction Disulfiram

Jonas, D. E., Amick, H. R., Feltner, C., et al (2014). Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review

and meta-analysis. Jama, 311(18), 1889–900. doi:10.1001/jama.2014.3628

Abstinence Oriented Pharmacological treatments

•  Similar efficacy worldwide •  Discontinuation of treatment lower in Europe

than in the rest of the world (acamprosate)

Efficacy of acamprosate in Japan

•  RCT in 327 Japanese patients with alcohol dependence assigned to treatment with either acamprosate (1,998 mg/d orally) or placebo for 24 weeks.

•  The primary endpoint was complete abstinence after 24 weeks of administration.

•  Acamprosate demonstrated superior efficacy vs placebo on the primary endpoint: abstinence was 47.2% in the acamprosate group compared with 36.0% in the placebo group (P = .039).

Other drugs for abstinence oriented treatments

Baclofen •  Very controversial •  Ongoing research just about to be published •  Low doses are not effective. High doses likely to be

effective Sodium Oxibate •  Registered in Austria and Italy •  Efficacy established for withdrawal •  Main trial results confidential and shortly available

Reduced drinking Pharmacological treatments

•  Nalmefene

•  Naltrexone? •  Topiramate? •  Gabapentin?

§  12-week, double-blind, RCT of naltrexone vs placebo in 221 individuals with AUD.

§  Participants randomly assigned to study treatment based on the presence of 1 or 2 copies of the Asp40 allele compared with those homozygous for the Asn40 allele (2  ×  2 cell design).

§  There was no evidence of a genotype  ×  treatment interaction on the primary outcome of heavy drinking

Reduction of alcohol drinking in young adults

•  A RCT conducted in an outpatient research center with 140 patients aged 18-25, who reported ≥ 4 HDD in the prior 4 weeks.

•  Intervention: naltrexone 25 mg daily plus 25 mg targeted (at most daily) in anticipation of drinking (n = 61) or daily/targeted placebo (n = 67). All participants received brief counseling every other week.

•  Primary outcomes were percent of HDD and percent days abstinent over 8 weeks. Secondary outcomes included number of DDD and percentage of days with estimated blood alcohol concentration (BAC) levels ≥ 0.08 g/dL.

•  Percent HDD (21.60 vs 22.90) and percent days abstinent (56.60 vs 62.50) did not differ by group.

•  Naltrexone significantly reduced the number of DDD (4.90 vs 5.90; P = .009) and percentage of drinking days with estimated BAC ≥ 0.08 g/dL (35.4 vs 45.7; P = .042).

•  There were no serious adverse events.

Topiramate vs placebo at week 14th

Pivotal Nalmefene RCTs

HDD: change from baseline in the 6-month studies – patients with at least high DRL at baseline and

randomisation 23 HDDs

11 HDDs

23 HDDs

10 HDDs

Difference: -3.7 HDDs, p=0.0010

Difference: -2.7 HDDs, p=0.0253

ESENSE 2 ESENSE 1

van den Brink et al. Alcohol Alcohol 2013;48(5):570–578; Data on file

MMRM (OC) FAS estimates and SE; *p<0.05, **p<0.01, ***p≤0.001; MMRM=mixed-effect model repeated measure; OC=observed cases; FAS=full analysis set; SE=standard error

TAC: change from baseline in the 6-month studies – patients with at least high DRL at baseline and

randomisation 113 g/day

43 g/day

102 g/day

44 g/day

Difference: -18.3 g/day, p<0.0001

Difference: -10.3 g/day, p=0.0404

ESENSE 2 ESENSE 1

MMRM (OC) FAS estimates and SE; *p<0.05, **p<0.01, ***p<0.001; MMRM=mixed-effect model repeated measure; OC=observed cases; FAS=full analysis set; SE=standard error van den Brink et al. Alcohol Alcohol 2013;48(5):570–578; Data on file

Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses

Leucht et al. Br J Psychiatry 2012;200:97–106

Nalmefene standardised effect size range

Standardized effect size (Cohen’s d)

Nalmefene1 HDDs TAC ESENSE 1 0.37 0.46

ESENSE 2 0.27 0.25

Alcohol treatment2,3 0.12 to 0.33

Antidepressants4 0.24 to 0.35

Antipsychotics4 0.30 to 0.53

1. Data on file; 2. Kranzler & Van Kirk. Alcohol Clin Exp Res 2001;25:1335–1341;

3. NICE. CG115. Alcohol dependence and harmful alcohol use: appendix 17d – pharmacological interventions forest plot. 2011;

4. Leucht et al. Br J Psychiatry 2012;200:97–106

Psychosocial treatments

The confrontational model •  Review of four decades of treatment outcome research. •  A large body of trials found no therapeutic effect relative to

control or comparison treatment conditions. •  Several have reported harmful effects including increased

drop-out, elevated and more rapid relapse. •  This pattern is consistent across a variety of confrontational

techniques tested. •  In sum, there is not and never has been a scientific evidence

base for the use of confrontational therapies.

WR. Miller, W. White; 2007

MoEvaEonal Interviewing

•  New golden standard for the psychological approach to addicEve behaviours

•  Radical change: – external confrontaEon as a technique vs internal confrontaEon as a goal

– PaEent centered – Spirit: partnership, compassion, evocaEon and acceptance

WR. Miller, S. Rollnick; 2012

Summary •  Statistically significant,

modest but robust effect: Odds ratio = 1.55

•  Effective: HIV viral load, dental outcomes, death rate, body weight, alcohol and tobacco use, sedentary behavior, self-monitoring, confidence in change, and approach to treatment.

•  Not particularly effective: eating disorder and some medical outcomes

Lundahl et al, 2013

A continuum of communication styles …

Informing Asking Listening

… that depends on how we use our communication abilities

Directing Guiding Following

Communication styles

Directing Guiding Following

Informing

Listening

Asking

Informing with choices

Empathic goal -oriented Listening

Asking open questions

Informing

Empathic listening

Asking

A continuum of styles

Goal Indications

Directing Getting precise information

Emergency Making a diagnosis

Guiding Eliciting and

reinforcing motivation to change

Where there is some ambivalence

Following Letting them express

an emotional experience

Emotional event

A Brief psychosocial approach: BRENDA

Volpicelli JR, Pettinati HM, McLellan AT, O’Brien CP. Combining medication and psychosocial treatments for addictions; the BRENDA Approach. New York, NY: The Guilford Press; 2001; Starosta et al. J Psychiatr Pract 2006;12:80–89

Needs expressed by the patient that should be addressed

Direct advice on how to meet those needs

Report to the patient on assessment

Empathetic understanding of the patient’s problem

Biopsychosocial evaluation

Assessing response/behaviour of the patient to advice and adjusting treatment

recommendations

11.60 11.60

Reduction in drinking using Brenda & TLFB (Sense study)

Monthly period Monthly period

HDDs TAC

Results from the control group

The Spirit of MI

Partnership Collaboration

Acceptance

Evocation

Compassion Spirit of

Acceptance

Accurate empathy

Autonomy support

Affirma2on

Absolute worth

Basic skills

Open questions

Reflective listening

Information / Advice Affirming

Summarizing

Strategical approach to promote behaviour change (4 basic processes)

Engaging

Focussing

Evoking

Planning

Miller & Rollnick; 2013

Summary & Conclusions •  AUD is a disease highly prevalent and with important medical,

psychiatric and social comorbidiEes •  Assessment should be conducted in an empathic style, from a

bio-‐psycho-‐social perspecEve and paEent centered •  Brief intervenEons, psychosocial treatments and various drugs

have shown efficacy in the treatment of alcohol dependence •  Combined medical and psychosocial treatments are the

preferred treatment strategy for alcohol dependence, within an Integrated Care approach

•  Integrated Care must be offered with a PaEent Centered approach, which implies the use of Shared Decision Making in a moEvaEonal style

Clinical strategies in the management of alcohol

dependence

Antoni Gual Addictions Unit

Psychiatry Dept. Neurosciences Institute Hospital Clínic de Barcelona. IDIBAPS

tgual@clinic.cat

Thanks for your attention. Questions are welcome.

Clinical strategies in the management of Alcohol Use Disorders. Lundbeck Institute, Copenhague march 2015

patient centered care

patient goals

patient values

shared decision

humanistic approach

assessment dimensions

individual patient preferences

drinking vs

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