Buprenorphine: Introduction (and Induction)

Adam J. Gordon, MD, MPH, FACP, FASAMUniversity of Pittsburgh School of Medicine

VA Pittsburgh Healthcare Systemadam.gordon@va.gov

Drug Abuse Treatment Act (DATA) of 2000

• Allowed “Qualified” physicians to treat opioid dependence outside methadone facilities1. Addiction certification from approved organization, or2. Physician in clinical trial of qualifying medication, or3. Complete 8-hour course from approved organization

• DEA issues (free) to qualifying physicians a new DEA number to use medication for opioid dependence

• As of today, only one medication formulation is approved for this use

Opioid Treatment: Changing Approach

Methadone Clinic Office-Based treatments• Criteria:

Withdrawal12 months use

• Criteria:DSM IVNo time criteria

• Dose regulated • MD sets dose

• Age > 18 • Age > 16

• Limited take homes • Take homes (30 days)

• Services “required” • Services must be “available”

Gordon, Counterdetails, 2006

Buprenorphine Properties• Partial-agonist

• Less reinforcing than a full agonist-milder effects• Easier withdrawal• Safety – overdose ceiling effect

• High affinity to the opiate receptor• Long duration of action (24-72hr)• Strong safety profile

• Little respiratory depression• Little overdose potential

-10 -9 -8 -7 -6 -5 -40

10

20

30

40

50

60

70

80

90

100

“Activity” or “Response”

Log DOSE

Full Agonist(Methadone)

Partial Agonist(Buprenorphine)

Antagonist (Naloxone)

Buprenorphine’s Properties:Partial Agonist

Gordon, Counterdetails 2006

Buprenorphine Properties:High Affinity

Gordon, Counterdetails, 2006

Buprenorphine Formulations• Formulations and routes

• BUPRENEX IV NOT for Opioid Dependence • Long history within Anesthesiology• History of use as mild analgesic

• SUBUTEX SL - Buprenorphine• 2 mg tablet• 8 mg tablet• Really one indication… (Pregnancy)

• SUBOXONE SL – Buprenorphine/Naloxone• 2mg/0.5mg tablet• 8mg/2mg tablet

• (Buprenorphine Transdermal)• (Buprenorphine Depot Injection)

Diversion potential: Buprenorphine/Subutex

Incorrect Incorrect CorrectRoute Oral IV (diversion) SublingualBuprenorphine Absorbed? NO YES YESNaloxone Absorbed? NO YES!!! NO !Outcome

(No Action)Pt:

MD: !

PO SLIV

Gordon, Counterdetails, 2006

Rationale for Naloxone+Buprenorphine(Suboxone)

Incorrect Incorrect CorrectRoute Oral IV (diversion) SublingualBuprenorphine Absorbed? NO YES YESNaloxone Absorbed? NO YES!!! NO !Outcome

(No Action)

(withdrawal)!

PO SLIV

Gordon, Counterdetails, 2006

Most often heard quote with Buprenorphine

“Doc, I feel normal”

• Treatment in normal medical settings:• Encourages continuity of medical/specialty care• Encourages relationship building with clinicians• Legitimize opioid dependence as a normal, treatable,

chronic illness

Buprenorphine: Treatment RetentionPe

rcen

t Ret

aine

d

0

20

40

60

80

100

1 2 3 4 5 6 7 8 9 1011121314151617

20% LO METH

58% BUP

73% HI METH

53% LAAM

Study Week

Johnson R, NEJM 2000

Buprenorphine: “Clean” UrinesM

ean

% N

egat

ive

Study Week

All Subjects

LO METH

BUPHI METH

LAAM

1 3 5 7 9 11 13 15 170

20

40

60

80100

19%

40%

39%

49%

Johnson R, NEJM 2000

Buprenorphine: Retention and Mortality

All Patients received group CBT Relapse Prevention, Weekly

Individual Counseling, 3x Weekly Urine Screens. n=20 per group

Treatment duration (days)

Remaining in treatment (nr)

0

5

10

15

20

0 50 100 150 200 250 300 350

Bup 6 day detoxBup Maintenance

4 deaths

0 deaths

Kakko J, Lancet 2003

Buprenorphine: Reduces Other Drug Use

Fudala, NEJM 2003

Opioid Dependence Treatment in Primary Care

Stein, JGIM 2005

At 24 weeks, 59% remained in treatment

Buprenorphine is not diverted

Cicero, NEJM 2005

OXYCODONE

METHADONE

BUPRENORPHINE

McLeod, SAMHSA 2005

Useful Websites

• Buprenorphine Information: www.buprenorphine.samhsa.gov

• NIAAA Web site: http://www.niaaa.nih.gov/• Medication information: http://www.suboxone.com• Physician Clinical Support System (PCSS)-

National Mentor for Physicians Treating Opiate Dependence. http://www.PCSSmentor.org