Transcript Phase II – relapse prevention

ALCOHOL USE
DISORDERS:
PHARMACOTHERAPY IN TREATMENT
Suzanne D. Turner MD, MBS, CCFP, ABAM
February 12, 2015
Alcohol Sales in Canada
• Total sales at beer and liquor in Canada: 18 billion
• Beer sales 47% of total alcohol sales in 2007
• 2.3 billion: number of litres of beer purchased by
Canadians
• $463 – amount of alcohol abuse costs every
Canadian a year, in lost productivity, health-care
costs and crime-related costs, according to a 2008
study by CAMH
http://www.cbc.ca/news/canada/story/2008/10/10/f-alcohol-numbers.html
Alcohol finding in primary care
• National (US) survey 649 primary care physicians
• Case record of patient with hx typical of alcohol
• Common diagnoses:
• Ulcer
• 84.3% for male patients; 46.8% for female patients
• Irritable bowel syndrome
• 58.6% for males; 70.1% for females
• Only 6.2% of physicians identified substance use as one of
five possible diagnoses
http://jama.jamanetwork.comarticle.aspxarticleid=18281
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The standard drink
• A standard drink = 14 g of ethanol
• 12 oz of regular beer or cooler (5% alcohol)
• 5 oz of table wine (12% alcohol)
• 1.5 oz of hard liquor (40% alcohol; 80
proof)
• A bottle of wine (~ 5 SD)
• A bottle of spirits (~ 17 SD)
Lower Risk Drinking Guidelines
• Men:
• Special Occasions:
• No more than 15 drinks / week
• Men: no more than 4 drinks
• No more than 3 drinks / sitting
• Women: no more than 3 drinks
• Women
• No more than 10 drinks / week
• No more than 2 drinks / sitting
18.7% of drinkers (14.4% of the total
population) exceed these guidelines
(2011)
Patients that exceed these guidelines
but don’t meet criteria for AUD are an
important population to target but not the
focus of today’s talk.
http://www.ccsa.ca/Eng/Priorities/Alcohol/Canada-Low-Risk-Alcohol-Drinking-Guidelines/Pages/default.aspx
Alcohol Use Disorder Diagnosis
• Alcohol is taken in larger amounts or for a longer period than intended
• Unsuccessful efforts to cut down or control alcohol use
• ++ time is spent in activities necessary to obtain alcohol, use or control alcohol use
• Craving or strong desire to use alcohol
• Failure to fulfill major role obligations at work, school or home
• Continued use despite having persistent or recurrent social or interpersonal problems
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causes or exacerbated by the effects of alcohol
Important social, occupational or recreational activities are given up or reduced
because of alcohol use
Recurrent alcohol use in situations where it is physically hazardous
Alcohol use is continued despite knowledge of having a persistent or recurrent physical
or psychological problem that is caused or exacerbated by alcohol
Tolerance
• a) A need for markedly increased amounts of alcohol to achieve intoxication or desired effect
• b)A markedly diminished effect with continued use of the same amount of alcohol
• Withdrawal:
• a)The characteristic withdrawal syndrome for alcohol
• b) Alcohol is taken to relieve or avoid withdrawal symptoms.
2-3 = Mild AUD; 4-5 = Moderate AUD; 6 or more = Severe AUD
Natural History of Alcohol Dependence
Treatment
• Phase I – detoxification (in/outpatient):
• Using Diazepam (or Lorazepam in cases of liver
dysfunction)
• Phase II – relapse prevention:
• Psychotherapy:
• Motivational Interviewing
• 12-step programs
• Cognitive-Behavioral Therapy (CBT)
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Despite these effective psychotherapies, 40-70% relapse
within 1 year after psychosocial treatment (Finney,1996)
• Pharmacotherapy:
PHASE II: RELAPSE
PREVENTION
Pharmacological Management
Pharmacological Interventions
• Disulfiram (Antabuse®)
• Naltrexone (Revia®)
• Acamprosate (Campral®)
• Topiramate (Topamax®)
• Baclofen
• Gabapentin (Neurontin®)
• Ondansetron (Zofran®)
Disulfiram: Antabuse®
• FDA Approval: 1949
• Prevents breakdown
of ethanol into acetate
• Acetalaldehyde is
toxic
• Leads to:
• Flushing
• Tachycardia
• Tachypnea
• Nausea and vomiting
• Headache
Disulfiram: Antabuse®
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11 RCT studies, 1527
subjects
• Disulfiram improves:
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short term abstinence
days until relapse
number of drinking days
Renewed interest
because of the efficacy
in cocaine population
Disulfiram: Antabuse®
Note: Not manufactured in Canada – only
available through a compounding pharmacy
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Patient must pay for it (~ $60-70 per month)
Approved dose: 250 mg/day
Can start with a loading dose of 500 mg x
1-2 weeks but most start with 250 mg
• Must not take within 12 hours of last drink
• Effects can last > 2 weeks
• Avoid EtOH in cough syrups, mouth wash,
etc
Disulfiram: Who should use it?
• Highly motivated
• Understands the risks of serious complications of
alcohol consumption while on the medication
• Lives with a partner/friend that can help to
ensure compliance
• Greater compliance associated with greater likelihood of
complete abstinence in study of 600 veterans
Fuller RK, et al. Disulfiram treatment of alcoholism. A Veterans Administration
cooperative study. JAMA 1986; 256: 1449-1455.
Disulfiram: Who should not use it?
• Any medical co-morbidity that may lead to fatality
if alcohol is consumed
• Unable to tolerate autonomic instability as a result
of Disulfiram
• IDDM
• Heart disease
• Seizure disorder
• Lives alone, poor social supports (unable to have
observed doses?)
• Unable to pay for compounding costs
Naltrexone: Revia®
• Opioid antagonists [naltrexone] for alcohol dependence
• Cochrane review: 50 studies, 7793 subjects
• Naltrexone is more effective than placebo:
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Reduces the risk of heavy drinking
• Decreases number of drinking days
• Decreases amount of alcohol consumed
• Decreases gamma-glutamyltransferase levels
• Injectable depots may be as effective as oral med
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Vivitrol, approved in the US, not yet in Canada
• Approved drug in Canada for alcohol dependence
• Needs EAP approval: Not available on general ODB
formulary
Naltrexone: Revia®
• Order AST, ALT, at least one test
for synthetic dysfunction
• Start at 25 mg per day x 3 days
then increase to 50 mg per day
• Can increase up to max dose of
150 mg per day
• No evidence for improved
efficacy for doses greater than 50
mg
• Continued therapy for 6-12
months
• Re-test LFTs at 2 weeks and 1
month
• Suitable for use in a reduction
paradigm
Naltrexone: Who should use it?
• Good first line medication for most people
• Especially good for heavy drinkers since can help reduce
before stopping medication
• Those that want moderation (rather than abstinence)
Naltrexone: Who shouldn’t use it?
• Regular opioid users: particularly those on OAST
• Those that don’t have drug insurance ($160/month)
• Transaminases > 3 times upper limit of normal
• Note: Check for synthetic dysfunction (cirrhosis is a
contraindication)
• Black box warning in the US for hepatotoxicity
• S/E can compound W/D: best to wait until abstinent x 4d
Acamprosate: Campral®
• Mechanism: Increases GABA neurotransmission
• Meta-analyses (Europe):
• increases abstinence over placebo
• Increased effect with treatment duration (3, 6 and 12 mo) [1, 2, 3, 4]
• Those that relapse while on Acamprosate: consume less
alcohol and with less frequency than those on placebo
• Also helps heavy drinkers (> 5 drinks per day) reduce
overall consumption
• No benefit to combining with naltrexone
1.
Kranzler HR, et al. Alcohol Clin Exp Res 2001: 25: 1335-1341; 2. Bouza C, et al. Addiction 2004:
99:811-828; 3. Chick J, et al. J Psychopharmacol 2003: 17: 397-402; 4. Mann K, et al. Alcohol
Cin Exp Res 2004: 28: 51-63; 5. Kiefer F, et al. Arch Gen Psychiatry 2003: 60: 92-99
Acamprosate: Campral®
• Renal excretion – suitable for those with elevated
transaminases and normal kidney function
• 666 mg PO TID (Two 333 mg tabs)
• Must have four days of abstinence before starting
medication *Required to state in EAP app
• ODB considers second line so must try Naltrexone first
and/or justify reasons for applying for Campral®
• *Suggest writing an accompanying letter if applying Campral®
discussing reasons for naltrexone contra-indication
• Also on EAP; not a general formulary drug
Topirimate: Topamax®
• Mechanism of action:
• Glutamate antagonist
• GABA agonist
• Benefits (found in single-centre and multi-centre trials):
• Reduction in drinks per day
• Reduction in drinking days/heavy drinking days
• Decrease in GGT levels
• Doses up to 300 mg total
• Start 25 mg PO BID (or qhs if concerned)
• Titrate weekly by 25 mg PO BID as tolerated
• No data in literature to support minimal dose needed
Johnson BA, et al. Lancet 2003; 361: 1677-1685; Johnson BA, et al. JAMA 2007,
298: 1641-1651.
Topirimate: Topamax®
• Who would you use this in?
• Patient’s that have “failed”/unable to tolerate first line treatments
• Concurrent mood disorder (?esp bipolar II)
• Who wouldn’t be suitable for this drug?
• Women of reproductive age
• Known teratogen
• Patient’s that are nervous of meds with any cognitive side effects
(or titrate very slowly)
• Patient’s with cognitive deficit or decline
• **Conflicting evidence for use for concurrent stimulant use**
What about topiramate and cocaine?
• Equivocal or conflicting results in multiple trials of
topiramate for stimulants (cocaine) (3, 4, 5)
• Not effective for reducing cocaine use amongst MMT
population (1)
• May help retain cocaine + alcohol patients in treatment
but not compelling reduction in cocaine use (2)
(1) Drug Alcohol Depend. 2014 Jul 1;140:92-100.; (2) Drug Alcohol Depend. 2013
Nov 1;133(1):94-9.; (3) Drug Alcohol Depend. 2014 May 1;138:177-84; (4) JAMA; J
Clin Psychiatry. 2010 May;71(5):634-48; Psychiatry. 2013 Dec;70(12):1338-46
Baclofen
• Mechanism of action: GABA-B receptor agonist
• Originally approved as anti-spasmodic
• Two smaller trials:
• 10 mg TID – well tolerated, more likely to remain abstinent at 1
month mark [1]
• Pts with liver cirrhosis – abstinence (71% vs 29%), doubling
number of abstinence days, well tolerated [2]
• Concerns re: misuse, overdose, withdrawal reactions
• Start 5 mg TID and titrate up by 5 mg TID – can use as
high as 80 mg total daily dose
1. Addolorato G, et al. Alcohol 2002; 37: 504-508; 2. Kiefer F, et al. Arch Gen
Psychiatry 2003: 60: 92-99
Baclofen
• Who would you use it in?
• ODB awaiting EAP approval
• Patient that wants med that is not associated “alcohol
dependence”; Need to inform off-label use
• Failed other first line therapies
• Who wouldn’t be suitable for this drug?
• Those with concurrent substance use disorders, especially
sedative dependence OR IVDU
• Renal dysfunction (renal clearance)
• Those who have difficulty with three times a day dosing
Gabapentin (Neurontin®)
• Mechanism of action: GABA receptor agonist
• Originally approved as anti-convulsant
• Randomized , double-blind, placebo-controlled trial
• Treated for w/d for at least 7 days
• Treatment: 300 mg PO BID x 4 weeks
• Treatment group:
• reduction in drinks per day,
• heavy drinking days,
• more abstinent days
Gabapentin (Neurontin®)
• Sleep-related effects of alcohol w/d significant trigger for
withdrawal
• Insomnia [1]
• May help with subacute w/d mediated insomnia
• Titrated to 1500 mg qhs x 6 weeks
• Delayed onset to heavy drinking over placebo
• No difference between sleep study outcomes and self-reports of
sleep between placebo and treatment
• Naltrexone + Gabapentin [2]
• 6 week trial
• Combined: longer interval to heavy drinking; fewer drinking days;
poor sleep assoc with more drinking in the naltrexone alone group
1.Brower K, Alcohol Clin Exp Res, 2008; 32: 1429-38.; 2. Anton RF, et al. AM J Psychiatry, 2011; 168: 709-717.
Gabapentin (Neurontin®)
• Who would you use it in?
• ODB awaiting EAP approval
• Patient that wants med that is not associated “alcohol
dependence”; Need to inform off-label use
• Failed other first line therapies
• Significant w/d mediated insomnia
• Who wouldn’t be suitable for this drug?
• Those with concurrent substance use disorders, especially
sedative dependence OR IVDU
• Unable to tolerate sedating effects or remember to take meds
multiple times per day
Ondansetron (Zofran®)
• Mechanism of action: 5-HT3 antagonist
• Originally approved as anti-emetic (chemotx)
• Two smaller trials:
• Early onset drinkers (before age 25): superior to placebo; inc
abstinent days; dec intensity of intake [1]
• Late-onset drinkers (after age 25): comparable to placebo
• Open label trial: same as above [2]
• No larger trials; ?only effective in early-onset drinkers
1. Johnson BA et al. JAMA 2000: 284: 963-971; 2. Kranzler et al. J Clin
Psychopharmacol 2001: 21: 72-77.
EAP: Counseling Options
• Individual therapy with Dina or Sharon
• MD counseling interventions
:
• CBT
• MI
• Solution-focused therapy
• Supportive counseling
• Document in the chart
• Concurrent disorder counseling
• SW/Psychology resources
• Trauma counseling
• Counseling through other agencies:
• TCAT (Peer Support Workers)
• Fred Victor
EAP: Relapse Prevention
• AA
• CAMH group therapies – self referral (Non-12 step based)
• SMH CRA Groups – Concurrent disorder focus
• Community Reinforcement Approach (CRA) is listed as a Best Practice for the
treatment of alcohol dependence by Health Canada
• Skills for understanding addiction in the context of their triggers to use, rewards
or functions of use, motivations for changing, and consequences of use.
• Uses positive reward systems within the client’s life such as: family or
significant others, social, recreational and vocational reward systems to assist
in developing new behaviors that are rewarding as well as competing with old
behaviors.
• Day Program at St. Joseph’s Health Centre
• Women’s Own Detox Day Program
• Community Outreach Worker: St. Michael’s Detox
• “Rehab”: In-patient/Out-patient; “aftercare”
• Pharmacotherapy
EAP: The logistics & Tips/Tricks
• Fax application
• Approval takes approximately 2 weeks
• Consider covering patient with 2nd line agent
• Baclofen 5 mg PO TID
• Gabapentin 100 mg TID (or 100 mg BID + 300 mg QHS)
• Topiramate 25 mg BID
• Transition to 1st line agent or continue 2nd line agent
• Give patient a copy of the EAP form to take to the
pharmacy**
• Send yourself a message in PSS when the application is
approx is 4 weeks prior to expiration to send in renewal
• Most patient’s will need 6-12 months treatment
• Some patient’s will need to continue indefinitely
Brief Intervention: 15 minutes
• Review low-risk drinking guidelines
• Link drinking to individual patient situation
• Emphasize that mood, sleep, energy level will improve
with reduced drinking
• Ask patient to commit to a drinking goal
• Reduced drinking or abstinence
• If unwilling to commit, continue to ask about drinking at every office
visit
• Assess values, motivational interviewing
• Monitor blood work at baseline and follow-up
• Have regular follow-up with alcohol at the top of the
agenda
Chermack, 1996; Blow, 1998
Brief Intervention with At-risk Drinkers
• Older, at-risk drinkers that received advice from their
primary care doctors about reducing consumption showed
significant REDUCTION in:
• 7-day alcohol use (Fleming, 1999)
• Episodes of binge drinking
• Frequency of excessive drinking (> 21 drinks/week)
• This difference was followed over time
• Differences still present after 12 months
• BOTTOM LINE: THESE PATIENTS LISTEN TO THEIR
DOCTOR AND RESPONDED TO BRIEF INTERVENTIONS
Goal Setting:
• Moderation:
• mild or even moderate AUD
• Target of abstinence:
• Pregnant women
• Health conditions exacerbated by alcohol
• Severe AUD
• Unable to reduce their heavy drinking
• Specific plan:
• Help the patient develop a step-by-step plan to meet their goal.
• For example: “This week I will start reducing my drinking by 1 drink per
setting to max 3 per day. I will not drink alone. I will not have my first
drink until 7pm. I will record my drinks on my day-planner. Next month
I will limit my maximum to 2 drinks per day and no more than 14 per
week.”
• Drinking log:
• Patients should record drinking log on calendar, day planner or an
smart phone app
Advice for reducing consumption:
• Start drinking later in the evening or night;
• have non-drinking days;
• take a time out between drinks;
• alternate alcoholic drinks with non-alcoholic drinks;
• eat before and while drinking;
• record drinks on a calendar or log book
• **At risk of w/d sz – reduce daily amt by 10% no more
than every 7 days***
Coping with cravings:
• Delay technique: "I will not act on this craving right away.
I will wait 5 (or 10 or 15) minutes to decide whether to act
on this craving.”
• Distract technique: Prepare a list of distractions ahead
of time e.g. call a friend or sponsor, go for a walk or run,
do some housecleaning. Select from list of distractions
when having a craving.
• Urge surfing technique: “Look at the urge as a wave,
surf it, riding it to the crest and down the other side.”
Alcohol Special Note:
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DSMV Diagnosis: Alcohol Use Disorder (mild, moderate, severe)
Anti-craving medication: Naltrexone, acamprosate, other, none
Thiamine: Y/N
Hepatitis B: HepBSAg (Neg/Pos); HepB Imm (Neg/Pos)
Hepatitis A: Imm (neg/Pos)
Hepatitis C: Neg/Pos
HIV: Neg/Pos
Immunizations:
Hep B – Date:
Hep A – Date:
Pneumococcal Vaccine:
Influenza:
dTap:
LFTs:
Driver’s Licence: Y/N – report to MOT: Y/N
Withdrawal Seizures: Y/N
• Delirium Tremens: Y/N
• High risk withdrawal: Y/N
Thank you
• Drs. Curtis Handford, Thea Weisdorf, Philip Berger, Maya
Nader and Lisa Graves
• Case discussions, patient coverage
• Drs. Mel Kahan and Sheryl Spithoff
• Alcohol Use Flow Sheet for Primary Care
• Drs. Wiplove Lamba and Tim Guimond
• CRA groups for concurrent disorder
STEP : DETOXIFICATION
Risk Factors for Alcohol Withdrawal
• Risk factors for ANY withdrawal:
• Former history of withdrawal
• BAL of 0.3 with consciousness
• Remaining conscious at this level indicates significant tolerance, and a
high likelihood of withdrawal symptoms if drinking is interrupted
• > 10 SD per day (lower for women)
• Risk factors for complicated withdrawal:
• Former history of withdrawal seizure or Delirium
• Traumatic brain injury
• Acute illness (increases the likelihood of DTs)
• Age 50
What benzo should you use?
In general: diazepam should be the standard
• less frequent daily dosing
• relatively steady serum levels -> better seizure protection
• the ability of these drugs to self-taper based on their long
half-lives
• Who’s at risk from diazepam use?
• Elderly (more metabolites and cognitive effects)
• Severe liver disease (read: cirrhosis/synthetic dysfunction)
Beware the patient with multiple w/d
• There are now at least nine studies
• that have found that an ever-increasing
• number of previous alcohol withdrawals
• increases the severity of withdrawal, particularly
• seizures and delirium tremens, and
• decreases responsiveness to benzodiazepines
• (Ballenger and Post 1978; Booth and Blow
• 1993; Brown et al. 1988; Gross et al. 1972;
• Lechtenberg and Worner 1990, 1992; Malcolm
• et al. 2000; Shaw et al. 1998; Worner 1996).
PHASE II: RELAPSE
PREVENTION
Non-pharmacological Management
12-step programs
• Studies in 1990s found:
• Patients who attended AA were significantly more likely to be
abstinent at 1 year after
• Same has been shown for NA and drug dependent patients
• AA attendance predicted abstinence
• Abstinence did not predict AA attendance
• How does it work?
• Strong social support for abstinence
• Consistent support leads to behaviour change and correlated with:
AA meeting attendance and sponsorship
Cavacuiti, C. “Principles of Addiction Medicine: The Essentials”
MD Referrals to 12 Step Programs
• 1996 Triennial AA member survey: only 8% of newcomers
reported coming to meetings via physician referral
• encourage patient to call AA OR
• Physician initiate contact with self help group in patients presence
(after obtaining permission)
• Study by Sisson & Mallams randomly assigned newly
diagnosed alcoholics to 2 types of referral
• Group 1 advised to go to meeting
• None attended a meeting
• Group 2 was put in direct contact with an AA member while in the
physician’s office
• Entire 2nd group attended a meeting
Who is likely to go to AA?
• More severe alcohol dependence
• More concern regarding drinking
• A greater commitment to abstinence
• Less support from spouse/partner
• A social network supportive of drinking
• A history of turning to others for support
• A greater desire to find meaning in life
Cavacuiti, C. “Principles of Addiction Medicine: The Essentials”
Making the Referral Work
• Give patients a prescription to attend a meeting
• Know the meetings in your area
• meetings have different personalities, if one does not work help
them find another
• Help patients make direct contact with patients in the
group
• Call the 12 step number
• Find a patient in your practice that will meet patients to take to
meetings
What to tell patients about meetings?
• Set expectations: what happens, how meetings are
structured
• Recommend socialization
• “arrive early and leave late”
• Encourage sponsorship
• temporary if necessary, same gender and 1year sobriety
• Get phone numbers at the meetings even if don’t have a sponsor
• Talk about fears and apprehension, help dispel myths
• Encourage frequent attendance versus coercion
• f/u visit to discuss experience at meetings
• If regular attendance, encourage finding a “home” group
and be active
• being active in program better predictor than number of meetings