De las intervenciones breves a los farmacos. malaga 2015

Abordaje de los problemas de alcohol: de las intervenciones

breves a los tratamientos farmacológicos

Dr Antoni Gual

[email protected]

REUNION DE LA RED DE TRASTORNOS ADICTIVOS

HOSPITAL REGIONAL UNIVERSITARIO DE MALAGA

6 DE MARZO DE 2015

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

Alcohol-attributable mortality (2004)

• Premature deaths are defined as deaths in the age

group between 15 and 64 years of age.

Men Women Total

% of premature deaths 13,9% 7,7% 11,9% 95% CI 8,1 – 19,2% 3,1 – 12,1% 6,5 – 16,9%

Number of premature deaths 94.500 25.000 119.500

95% CI 55.500 – 130.500 10.500 – 40.000 66.000 – 170.500

Proportion One in 7 One in 13 One in 8

Alcohol-attributable premature deaths in the EU 2004 by sex and main causes

DetrimentaleffectsMen

#sWomen

#sMen

%Women

%

Cancer 17,358 8,668 15.9% 30.7%

Cardiovasculardisease

(otherthanIschemicheart

disease)7,914 3,127 7.2% 11.1%

Mentalandneurologicaldisorders

10,868 2,330 9.9% 8.3%

Livercirrhosis 28,449 10,508 26.0% 37.2%

Unintentionalinjury 24,912 1,795 22.8% 6.4%

Intentionalinjury 16,562 1,167 15.1% 4.1%

Otherdetrimental 3,455 637 3.2% 2.3%

Totaldetrimental 109,517 28,232 100.0% 100.0%

Beneficialeffects

Ischemicheartdisease 14,736 1,800 97.8% 61.1%

Otherbeneficial 330 1,147 2.2% 38.9%

Totalbeneficial 15,065 2,947 100.0% 100.0%

Alcohol-attributable Alcohol-attributable (net) Heavy drinking Alcohol dependence

Men 16,1% 13,9% 11,1% 10,7%

Women 8,5% 7,7% 5,3% 3,7%

Total 13,6% 11,8% 9,2% 8,4%

Men Women Total

25

20

15

10

5

0

Per

cen

tage

of

dea

ths

Heavy drinking accounts for 78 % of the net burden

Rehm et al. 2012. Alcohol consumption, alcohol dependence, and attributable burden of disease

Alcohol-attributable deaths for people 15 to 64 years of age

Alcohol dependence incurs an enormous financial burden on society

Total = €155.8 billion

€21.4

€6.3

€45.2

€11.3

€17.6

€18.8

€15.1

€7.5

€12.6

HealthTreatment/preventionMortalityAbsenteeismUnemploymentCrime - policeCrime - defensiveCrime - damageTraffic accident damage

Breakdown of costs, in billions, attributable to alcohol-related problems in the EU in 2010

Rehm et al, 2012 Social costs defined as costs to society, i.e., all costs arising from alcohol consumption that are not borne exclusively by the drinker, such as spending on the drinks

Alcohol-attributable harm to others

• Harm to others includes three major items, with different prevalence: – transport injuries – physical violence or homicide – babies born with low birth weight due to the mother’s drinking

(FASD)

• In the EU in 2004, the harm to others caused by alcohol consumption included – 7,710 deaths, – 191,151 potential years of life lost due to premature mortality – 27,410 years of life lost due to disability – 218,560 DALYs

• Overall, the above numbers are clear underestimates.

Prevalence of Alcohol Dependence (AD) and access to treatment. Data from the APC study

AD diagnosis by GP

Patients visited by the GP 13,003

Patients identified as alcohol dependent 5.1% (663)

Patients who received professional help 21.8% (n=145)

• Six EU countries • GPs interviewed about

patients seen in a given day • Patients interviewed with

standardized questionnaires when they exit consultation

Rehm J, et al. Ann Fam Med. 2015.

The double gap

Patients with AUD in PHC

settings

Risky drinkers offered brief

advice to reduce

Alcohol dependent offered treatment

1st GAP

Screening or early identification?

• Screening: Strategy used in a population to identify an unrecognised disease in individuals without signs or symptoms.

• Targeted screening: Screening limited to selected population (because of high risk or high vulnerability)

• Early identification: Evaluation of patients in whom signs of alcohol playing a negative role in a case history are present

The AUDIT-C

1. How often do you have a drink containing alcohol?

2. How many standard drinks containing alcohol do you have on a typical day when drinking?

3. How often do you have six or more drinks on one occasion

0) Never 1) Less than monthly 2) Monthly

3) Weekly 4) Daily or almost daily

The AUDIT-C

1. How often do you have a drink containing alcohol?

2. How many standard drinks containing alcohol do you have on a typical day when drinking?

3. How often do you have six or more drinks on one occasion

0) Never 1) Less than monthly 2) Monthly

3) Weekly 4) Daily or almost daily

Cut off point for Hazardous drinking:

• 4 or more in women • 5 or more in men

Isn’t this a brief intervention?

What is a Brief Intervention?

It usually consists of a package involving:

• information on drinking risk levels,

• the status of the patient’s own drinking in relation to those levels,

• encouragement to cut down and set a date for doing so

• and perhaps a few simple hints on how cutting down might best be achieved

Heather, N., 2010

What is the evidence ?

1. Do brief interventions work? Efficacy studies.

2. Do brief interventions work in the real world of primary care? Effectiveness trials.

3. Are they cost-effective? Cost-effectiveness studies.

4. What factors promote widespread adoption of brief interventions into routine practice? Implementation trials.

5. Wider roll-out work: Demonstration studies.

O’Donnell et al, 2014

1. Efficacy studies

• 23 trials

• Best evidence for 10-15 min BIs and multicontacts

• Compared to controls:

• Consumption decreased by 3,6 drinks per week from baseline

• Heavy drinking episodes reduced by 12%

• 11% reported drinking below recommended limits

Jonas et al, 2012

2. Effectiveness trials

• 24 systematic reviews

• Brief alcohol interventions are effective when delivered in primary healthcare

• Brief alcohol intervention equally effective across different countries and different health care systems

• Insuficient evidence in young and older adults

• Optimum length, frequency and content unknown

O’Donnell et al, 2013

3. Cost-effectiveness studies

Agnus et al, 2014, Unpublished

3. Cost-effectiveness studies Cost-effective Highly cost-effective Cost-saving

Bulgaria Estonia Romania

Croatia Latvia Lithuania Hungary Slovakia Poland Czech Republic Germany Italy Finland

Portugal Malta Cyprus Greece Spain France Austria Belgium Ireland Luxembourg Sweden Netherlands Denmark United Kingdom

Agnus et al, 2014, Unpublished

4. Implementation trials

• Cluster randomized factorial trial

• 120 PHC practices in 5 countries

• Objective: to test three strategies that might increase implementation of EIBI for excessive alcohol consumption in PHC:

– Training and support (Education)

– Financial incentives (Money)

– E-Brief Intervention (Time)

Keurhorst et al, 2013

4

8

12

16

20

24

28

Baseline Week 1-4 Week 5-8 Week 9-12 Follow-up

TS-

TS+

FR-

FR+

eBI-

eBI+

125%*** > FR-

69%*** > TS-

Anderson et al, 2014, Submitted

4

8

12

16

20

24

28

32

Baseline Week 1-4 Week 5-8 Week 9-12 Follow-up

TSFR-

TSFR+

TSeBI-

TSeBI+

FReBI-

FReBI+

TSFReBI-

TSFReBI+

280%*** > TSFR-

Anderson et al, 2014, Submitted

Implementation trials

1. Two hours of training led to more interventions being delivered.

2. Modest financial reimbursement led to more interventions being delivered. Work optimally when fine-tuned to country-specific contexts

3. A combination of training and support and financial reimbursement led to more interventions being delivered than either strategy alone

Anderson et al, 2014, Submitted

5. Demonstration studies: screening in PHC in Catalonia

Colom et al, 2014. Data on file

0

10

20

30

40

50

60

70

2005 2006 2007 2008 2009 2010 2011

Lleida

Tarragona

Barcelona

Girona

MetropolitanaSud

MetropolitanaNord

Caralunyacentral

AltPirineu

Terresdel'Ebre

Total

Health areas in Catalonia

When do opportunistic BIs become motivational?

• Ask for permission to Assess consumption with a brief screening tool

• Ask for permission to give Advise to patients to reduce their consumption

• Agree on individual goals through negotiation

• Assist patients with acquiring the motivations, self-help skills, or supports needed for behaviour change using MI microskills

• Offer to Arrange follow-up

25

A Brief Intervention is..

A short advice given by a health

professional to a patient

But a Brief Motivational Intervention

is

A short conversation between a health

professional and a patient

Two different MBI approaches

Assessment feedback

• Feedback of assessment as the primary means of structuring the conversation and as the basis to elicit change talk

Conversational style

• Series of conversational exercises expected to be helpful in eliciting change talk on relevant material

McCambridge J, 2002

Why do MBI work?

• Life events (raise awareness)

• Assessment (raise awareness)

• Internal discrepancies (importance)

• Taking steps - planning (confidence)

The double gap

Patients with AUD in PHC

settings

Risky drinkers offered brief

advice to reduce

Alcohol dependent offered treatment

1st GAP 2nd GAP

• 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:

H

S

S

S

S

S

H

H

S - pSychosocial H - pHarmacological

H

H S

S

Pharmacological treatments

70

Alcohol related problems

Pharmacological interventions

70

Alcohol related problems

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

51

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

Other drugs for abstinence oriented treatments

Baclofen • Very controversial

• Ongoing research just about to be published

• High doses likely to be effective

Sodyum Oxibate • Registered in Austria and Italy

• Efficacy stablished for withdrawal

• Main trials finished but not published yet

Reduced drinking

Pharmacological treatments

• Nalmefene

• Naltrexone?

• Topiramate?

• Gabapentin?

Topiramato vs placebo a las 14 semanas

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, ***p0.001; 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

Motivational Interviewing

• New golden standard for the psychological approach to addictive behaviours

• Radical change:

– external confrontation as a technique vs internal confrontation as a goal

– Patient centered

– Spirit: partnership, compassion, evocation 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

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)

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

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

• Double gap: identification and treatment rates are very low

• BIs efficacy and effectiveness established but implementation is difficult

• Pharmacological treatments have widened their scope

• Pychosocial treatment remains the basis of a good clinical approach to AUDs.

Final remarks

Abordaje de los problemas de alcohol: de las intervenciones breves a los tratamientos

farmacológicos

Dr Antoni Gual

[email protected]

REUNION DE LA RED DE TRASTORNOS ADICTIVOS

HOSPITAL REGIONAL UNIVERSITARIO DE MALAGA

6 DE MARZO DE 2015

MUCHAS GRACIAS !!!