DIFFICULT TO TREAT ALCOHOL DEPENDENCE: DIFFICULT PATIENT, POOR EVIDENCE BASE OR LIMITED RESOURCES?

Abhijit NadkarniIndian Psychiatric Society, West Zone CME

17th June 2012

DIFFICULT PATIENT

POOR EVIDENCE

LIMITED RESOURCES

How do we define difficult to treat alcohol dependence?

• PATIENT CHARACTERISTIC

• NATURE OF ILLNESS• LIMITATION OF SCIENCE

WHAT USUALLY HAPPENS• Mesa Grande project (Miller et al,

2001)• 87% reduction in alcohol

consumption• Abstinence on 80% of days• 24% abstinent for the entire year• Similar proportion resumed

controlled, problem-free drinking.• Most relapses occurred within the

first 3 months. • Results are supported by other

studies (Ludbrook et al, 2005).

WHO MIGHT DO WELL

• Age, gender, socioeconomic status etc

• Having a job• Supportive relationship• Most powerful therapy

variable is therapist empathy

• Compliance with medication

WHO MIGHT DO WELL

• Readiness to change behaviour

• Patients confidence in tackling the drink problem

• How pro drinking the social circle

WHO MIGHT NOT DO WELL

• LIFE CIRCUMSTANCES• COMPLIANCE WITH

TREATMENT • COMORBID MENTAL

HEALTH PROBLEMS• PERSONALITY

DISORDER• NATURE OF THE

ILLNESS!!!

REMEMBER……….

AD often has a persistent course, as reflected by observed annual remission rates of only 2–6% in treated alcoholics

WHAT CAN WE DO IF THERE IS POOR RESPONSE?

WILL PSYCHOSOCIAL INTERVENTIONS HELP?

MESA GRANDE

• Mesa Grande project (Miller 2003)• 381 randomised controlled trials of different

types or intensities of treatment• Cumulative evidence score was calculated• Brief interventions and motivational

enhancement therapy received ranks of one and two respectively

PSYCHOSOCIAL• TSF• MET• CBT• Social skills training• Community reinforcement approach• SBNT• Contingency management• Cue exposure• Residential rehabilitation• BCT

OFFER MET IF NOT PROVIDED BEFORE

• Even people with severe dependence should be offered MET as the first stage in a stepped programme of care in specialist services (Raistrick 2006).

WOULD INCREASING THE INTENSITY OF PSYCHOTHERAPY HELP?

Treatment Intensity

• Less intensive treatments are as effective as the more intensive options (Chick et al, 1988)

• MET = TSF = CBT (Project MATCH Research Group, 1997)

• MET = SBNT (UKATT, 2005)

DOES AA HAVE ALL THE ANSWERS?

Randomised controlled trials have not found AA groups or the twelve-step approach to be superior to alternative treatments (Nowinski et al, 1992; McCrady et al, 1996)

IS TREATMENT MATCHING THE ANSWER?

• NO CONCLUSIVE ANSWERS FROM PROJECT MATCH

WHAT IS DEFINITELY OUT• Brief interventions • Moderately effective in the

non-treatment-seeking groups, especially for those with less severe alcohol problems (effect sizes of 0.14–0.67 were reported).

• No evidence that opportunistic brief interventions are effective among people with more severe alcohol problems and levels of dependence

MEDICATIONS

Disulfiram• Hailed as a ‘cure’ for alcoholism. • Hughes & Cook (1997) reviewed

24 outcome studies for oral disulfiram and 14 using implants from 1967 to 1995. Most studies were flawed and reported no significant benefits for disulfiram.

• With the pills, a decision whether to drink or not still has to be made, but only once a day.

• Tablets implanted subcutaneously sensitise the patient for about two weeks.

CLIENT CONTINUES TO DRINK DESPITE DISULFIRAM

• RCTs that have demonstrated efficacy (and shown near 100% two-year abstinence) have entailed recruiting a supervisor

• Patients are encouraged to ask their partner, a nurse or welfare officer at work, or a nurse at the health centre or the clinic to see them take the Disulfiram.

Naltrexone• Reduced risk of relapse, at least for

three months.• Effect size for percentage of days

drinking 0.42- 0.60 (Volpiceli et al, 1995)

• As good or as bad as Fluoxetine for depression!!!!

• Dysphoria a concern………………….but not in AUD

• Naltrexone appears to be an effective and safe strategy in alcoholism treatment

• Promising results with injectable long acting naltrexone

Nalmefene

• Opiate antagonist• Better oral availibility• No dose related liver toxicity• Active at more receptors• Better than placebo• No direct comparison with Naltrexone• Large multi centre trial currently in progress

Acamprosate• Chick et al (2000) reported the largest

single study of acamprosate: the United Kingdom Multicentre Acamprosate Study.

• Overall adherence to treatment was poor (35%)

• No significant difference in drinking outcomes between groups at 6 months

• Recent studies have shown more encouraging results

• Compared to placebo, acamprosate• Significantly reduce the risk of any

drinking RR 0.86 (95% CI 0.81 to 0.91)• Bias in favour of more highly motivated

patients.• Better results in Europe than USA

IS COMBINING THE TWO THE ANSWER

Combinations

• Naltrexone + Sertraline• Nalmefene + Sertraline• Disulfiram +

Acamprosate• Acamprosate +

Naltrexone

• Although the two largest trials of acamprosate and naltrexone showed no significant benefits (Chick 2000; Krystal 2001), a meta-analysis of studies (Bouza 2004) has demonstrated a beneficial therapeutic effect.

• There are unconfirmed suggestions that the two may act differently and may therefore act additively if combined.

SHOULD WE TRY THE ‘DOOSRA’

Topiramate

• Topiramate superior to placebo on all drinking measures.

• Decreased percentage of heavy drinking days (mean difference of 16.19%; CI, 10.79%–21.60%)

• Superior to placebo but not to naltrexone.

SSRIs and Quetiapine

• Limited and inconsistent evidence

Others

• Baclofen, a GABA receptor agonist that may inhibit cravings- Inconsistent results

• Two studies found ondansetron, a 5-HT3 receptor antagonist that can block the rewarding effects of alcohol, effective compared to placebo

• Tiapride-a D2 dopamine antagonist• Clozapine and aripiprazole in dual diagnosis• Olanzapine to reduce craving for alcohol in

nonschizophrenic, alcohol-dependent individuals

• Divalproex and lamotrigine in dual diagnosis

IMPORTANT

• However, none of the treatments described here is recommended as a solo therapy.

• Social and psychological factors in treatment for alcohol dependence are crucial.

SHOULD WE COMBINE MEDICATIONS AND PSYCHOTHERAPY?

COMBINE• Anton 2006• 16-week RCT• 1383 recently abstinent alcohol-dependent volunteers • Naltrexone, or acamprosate, or naltrexone plus acamprosate or placebo

(all with or without a ‘combined behavioural intervention’ based on cognitive–behavioural therapy), or the behavioural intervention alone

• 1 year follow up• All groups showed substantial improvements• Acamprosate showed no evidence of efficacy above placebo, with or

without the behavioural intervention• Naltrexone plus the behavioural intervention produced the best efficacy• Placebo pills and a meeting with a healthcare professional had a more

positive effect than the behavioural intervention alone

Treat coexisting disorders

• Recurrence and persistence rates are significantly higher in patients with baseline depressive and anxiety disorders

• Sertraline + Naltrexone

HARM REDUCTION

CONTINUING CARE

• Individual, telephone, and group therapy• Brief check-ups• Mutual-help meetings.• Aggressive outreach attempts • Use of low burden service delivery systems

such as the telephone

THE BASICS

• Build a trusting relationship and work in a supportive, empathic and non-judgmental manner

• Encourage families and carers to be involved in the treatment and care of people who misuse alcohol to help support and maintain positive change.

DO NOT

• ….use antidepressants (including selective serotonin reuptake inhibitors [SSRIs]) routinely for the treatment of alcohol misuse alone.

• Benzodiazepines should only be used for managing alcohol withdrawal and not as ongoing treatment for alcohol dependence.

Make it hard to stay away

• Cost less virtues: pleasant and respectful atmosphere, clear communication of staff and patient and staff roles/responsibilities, empathy and concern for patient welfare

• Overcoming practical barriers to access e.g. transport

• Appointment reminders• Rapid response to missed appointments

IS A PARADIGM SHIFT IN DEFINING RECOVERY NEEDED

Controlled drinking?• First suggested by Davis (1962).• Limit on alcohol consumption

provided it does not lead to signs of dependence, intoxication or social, legal or health problems.

• Young, socially stable drinkers with short, less severe drinking histories

• Not to be recommended for people with heavy dependence or those with protracted alcohol problems (Rosenberg, 1993).

• Clients themselves decide and are often uninfluenced by the agenda set by the therapists

EXPERIMENTAL• Novel mechanisms of action• Rodent models of alcohol• Kudzu root extract (Benlhabib,

Baker, Keyler, & Singh, 2004)• Cannabinoid receptor antagonist

rimonabant• (SR141716A; Cippitelli et al., 2005)• Neuropeptide-Y receptor

antagonist L-152,804 (Schroeder, Overstreet, & Hodge, 2005)

• CRF antagonists antalarmin and• R121919 (Funk, Koob, Lee, Rice, &

Zorrilla, 2007)

FUTURE• Facilitating the use of

alcohol medications in real-world clinical practice

• Discover and validate new molecular targets for the treatment of alcohol dependence

• Advance personalized medicine in the pursuit of new compounds

‘‘WHAT TREATMENT, BY WHOM, IS MOST EFFECTIVE FOR THIS INDIVIDUAL WITH THAT SPECIFIC PROBLEM, AND UNDER WHICH SET OF CIRCUMSTANCES?’’

Gordon Paul’s (1967) iconic question: