Pharmacotherapy of Addictions

1
Pharmacotherapy of Addictions

• David W. Oslin, MD
• University of Pennsylvania, School of Medicine
• And
• Philadelphia, VAMC

Hazelden Research Co-Chair on Late Life
Addictions
2
Focus on Abuse and Dependence
Participating in Specialty Care
Problems / Abusive Drinking
Dependent
3
Pharmacotherapy a real option for treatment

• Alcohol dependence
• Naltrexone
• Acamprosate
• Antabuse
• Opioids
• Buprenorphine
• Methadone
• Cocaine
• ?
• Nicotine
• Nicotine replacement
• Bupropion
• Varenacline

4
Naltrexone

• FDA approved for the treatment of alcohol
  dependence
• Functions as an opioid receptor antagonist (mu gtgt
  delta or kappa)
• Development was an example of bench to bedside
  translational science (opioid effects on reward
  pathways)

5
Randomized Placebo Controlled Naltrexone Trials
Studies supporting efficacy Studies supporting efficacy Studies supporting efficacy Studies not supporting efficacy Studies not supporting efficacy Studies not supporting efficacy
Study Ss Notes Study Ss Notes
Volpicelli et al 1992 70 None Oslin et al 1997 44 Older
OMalley et al 1992 97 None Kranzler et al 2000 183 None
Volpicelli et al 1997 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
6
Acamprosate

• Mechanism of action is unknown GABA vs NMDA
• Low rate of adverse effects
• Usual dose 2 gm/d divided 4 times/day

7
SSRIs 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?

8
Treatment Algorithm
9
Appropriate Candidates for Treatment

• Adults with Alcohol Dependence
• No Liver Failure/Active Hepatitis
• No Current Opioid Use
• Not Pregnant

10
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

11
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

12
Pretreatment Work-up

• Education - alcohol dependence as a disease
• Physical Exam
• Laboratory Testing
• Serum Transaminases
• Total Bilirubin
• Pregnancy Test
• Urine Toxicology Test
• Medical History
• Substance Use/Abuse History
• Mental Health Status

13
Starting Naltrexone

• Education
• expected benefits
• goals for treatment
• importance of compliance
• adverse effects
• interactions with alcohol
• safety card

14
Pharmacotherapy a real option for treatment

• Alcohol dependence
• Naltrexone
• Acamprosate
• Antabuse
• Opioids
• Buprenorphine
• Methadone
• Cocaine
• ?
• Nicotine
• Nicotine replacement
• Bupropion

15
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?

16
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?

17
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?

18
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

19
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

20
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

21
Preparation for Induction

• Are all necessary assessments completed?
• H P
• ECG
• Labs
• Psychosocial assessment
• Consent for treatment and, If necessary,
  treatment contract
• Is patient education for induction completed?

22
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?

23
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.

24
Administrative Issues

• Availability of physician
• Clinic Directive
• Malpractice
• Availability of lab support
• Monitoring (psychosocial platform)