Transcript Addiction Pharmacotherapy

Pharmacotherapy of Addictions
David W. Oslin, MD
University of Pennsylvania, School of Medicine
And
Philadelphia, VAMC
Hazelden Research Co-Chair on Late Life Addictions
Focus on Abuse and Dependence
Participating
in Specialty Care
Problems /
Abusive
Drinking
Dependent
Pharmacotherapy – a real option for
treatment

Alcohol dependence
 Naltrexone
 Acamprosate
 Antabuse

Opioids
 Buprenorphine
 Methadone

Cocaine
 ?

Nicotine
 Nicotine replacement
 Bupropion
 Varenacline
Naltrexone
 FDA approved for the treatment of alcohol
dependence
 Functions as an opioid receptor
antagonist (mu >> delta or kappa)
 Development was an example of bench to
bedside translational science (opioid
effects on reward pathways)
Randomized Placebo Controlled Naltrexone Trials
Studies supporting efficacy
Study
Studies not supporting efficacy
# Ss
Notes
Volpicelli et al 1992
70
None
O’Malley et al 1992
97
Volpicelli et al 1997
Study
# Ss
Notes
Oslin et al 1997
44
Older
None
Kranzler et al 2000
183
None
97
None
Krystal et al 2001
627
VA only
Kranzler et al 1998
20
Depot
Lee et al 2001 (Singapore)
53
None
Anton et al 1999
131
None
Gastpar et al 2002 (Germ.)
171
None
Chick et al 2000 (UK)
169
Adherence
Kranzler et al 2004
315
Depot
Monterosso et al 2001
183
None
Killeen et al 2004
145
None
Morris et al 2001 (Australia)
111
None
Oslin et al in press
240
None
Heinala et al 2001 (Finland)
121
Nonabst.
Latt et al 2002 (Australia)
107
None
Ahmadi and Ahmadi 2002 (Iran)
116
None
Guardia et al 2002 (Spain)
202
None
Balldin 2003
118
None
Kiefer et al 2003 (Germany)
160
None
Kranzler et al 2003
153
None
Kranzler et al 2004
315
For drinking not
relapse
Anton et al 2004
270
None
Garbutt et al 2005
627
Depot / males
Acamprosate
 Mechanism of action is unknown – GABA
vs NMDA
 Low rate of adverse effects
 Usual dose 2 gm/d divided 4 times/day
SSRI’s and other serotonergic agents
 By all accounts serotonin is important
in addictions
 But results from treatment trials?
 Some say yes, some say no, others
maybe.
 Does the target audience matter?
Treatment Algorithm
Appropriate Candidates for Treatment
 Adults with Alcohol Dependence
 No Liver Failure/Active Hepatitis
 No Current Opioid Use
 Not Pregnant
Naltrexone Should Be Used for
Patients With:
 Prior treatment failure
 High level of interest in biomedical therapies
 Low level of interest in traditional psychosocial therapies
 Cognitive impairment
 In most alcohol-dependent patients
 Consider depot formulation for added adherence
Consider Naltrexone as a Second Line
Treatment in Patients Who are:
 Pregnant
 Adolescent
 Experiencing Active Liver Disease
 Experiencing Severe Medical Problems
 Known to be Very Non-Compliant (start on depot)
 Requiring Opioid Medications
 About to have Surgery
Pretreatment Work-up
 Education - alcohol dependence as a disease
 Physical Exam
 Laboratory Testing
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Serum Transaminases
Total Bilirubin
Pregnancy Test
Urine Toxicology Test
 Medical History
 Substance Use/Abuse History
 Mental Health Status
Starting Naltrexone
 Education
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expected benefits
goals for treatment
importance of compliance
adverse effects
interactions with alcohol
safety card
Pharmacotherapy – a real option for
treatment
 Alcohol dependence
 Naltrexone
 Acamprosate
 Antabuse
 Opioids
 Buprenorphine
 Methadone
 Cocaine
 ?
 Nicotine
 Nicotine replacement
 Bupropion
Appropriateness for Buprenorphine
Consider these factors
1. Does the patient have a diagnosis of
opioid dependence?
2. Is the patient interested in
buprenorphine treatment?
3. Does the patient understand the
risks/benefits of buprenorphine
treatment?
Appropriateness for Buprenorphine
Consider these factors (continued)
4. Is he/she expected to be reasonably
compliant?
5. Is he/she expected to follow safety
procedures?
6. Is the patient sufficiently
psychiatrically stable?
Appropriateness for Buprenorphine
Consider these factors (continued)
7. Are the psychosocial circumstances of
the patient stable and supportive?
8. Can the clinic provide the needed
resources for the patient (either on or off
site)?
9. Is the patient taking other medications
that may interact with buprenorphine?
Appropriateness for Office-based Buprenorphine
Patient is less likely to be an appropriate
candidate for office-based buprenorphine
treatment
1. Dependence on high doses of
benzodiazepines, alcohol, or other CNS
depressants
2. Significant psychiatric co-morbidity
3. Active or chronic suicidal or homicidal
ideation or attempts
Appropriateness for Office-based Buprenorphine
Patient is less likely to be an appropriate
candidate for office-based buprenorphine
treatment (continued)
4. Multiple previous treatments and relapses
5. Non-response to buprenorphine in the
past
6. Patient needs cannot be addressed with
existing office-based resources
Appropriateness for Office-based Buprenorphine
Patient is less likely to be an appropriate
candidate for office-based buprenorphine
treatment (continued)
7. High risk for relapse
8. Pregnancy
9. Current medical condition(s) that could
complicate treatment
10. Poor support systems
Preparation for Induction
 Are all necessary assessments completed?
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H&P
ECG
Labs
Psychosocial assessment
Consent for treatment and, If necessary,
treatment contract
 Is patient education for induction completed?
Preparation for Induction
 Determine when, how and where you will start
medication
 Advise patient not to use opioids for an
appropriate amount of time prior to first dose
 Ensure that patient has arranged for
transportation home from appointment for first
dose
 Other contingency preparations?
Summary
 Buprenorphine and buprenorphine/naloxone
are effective for the treatment of opiate
dependence in the office setting.
 Physicians can easily become qualified to
prescribe buprenorphine.
 Managing patients within the office setting can
be done with existing resources and minimal
difficulty.
Administrative Issues
 Availability of physician
 Clinic Directive
 Malpractice
 Availability of lab support
 Monitoring (psychosocial platform)