Buprenorphine and the NIDA CTN: Research to Practice

Walter Ling & Richard Rawson ISAP/UCLA

XIII World Congress of PsychiatrySeptember 14, 2005

Cairo, Egypt

rrawson@mednet.ucla.eduwww.uclaisap.org

Potentially lethal dosePositive effect

=

addictive

potential

Negative effect

Full agonist -morphine/heroin

hydromorphone

Antagonist - naltrexone

dose

Antagonist + agonist/partial agonist

Agonist + partial agonist

Super agonist -fentanyl

Partial agonist - buprenorphine

Mu efficacy and opiate addictionMu efficacy and opiate addiction

Buprenorphine: Clinical Pharmacology

Partial Agonist• high safety profile/ceiling effect• low dependence

Tight Receptor Binding• long duration of action• slow onset mild abstinence

Good Effect

0

20

40

60

80

100

p 0.5 2 8 16 32

Buprenorphine (mg)

Pea

k S

core

3.75 15 60

Methadone (mg)

Respiration

02468

1012141618

p 1 2 4 8 16 32

Buprenorphine (mg)

Bre

ath

s/m

inu

te

Intensity of abstinence

60

50

40

30

20

10

0

Him

mel

sbac

h s

core

s

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Buprenorphine

Morphine

Days after drug withdrawal

Buprenorphine detoxificationin community clinics

Buprenorphine : Very brief pharmacologyCTN Protocols 0001 & 0002Buprenorphine vs clonidine:

Inpatient detoxificationOutpatient detoxificationTreatment success /Number needed to treat

Looking ahead:Implementation: Successes and barriers

The rest of the world

The First CTN Protocols

• Short term inpatient detoxification– Buprenorphine/naloxone vs clonidine– (CTN 0001)

• Short term outpatient detoxification– Buprenorphine/naloxone vs clonidine– (CTN 0002)

Study Design

Buprenorphine/Naloxone13 days detoxification

Open Randomized StudyBup/Nx:Clonidine = 2:1

Clonidine13 days detoxification

Joint Probability

N remaining in treatment

X

Total N of subjects

N giving drug free urines

N remaining in treatment

Demographics 0001 (Inpatient)Bup/Nx Clonidine Total

Sex No. (%)

Male

Female

47 (61)

30 (39)

21 (58)

15 (42)

68 (60)

45 (40)Race No. (%)

White

Black

Hispanic

Other

43 (56)

15 (19)

12 (16)

7 (9)

20 (56)

7 (19)

6 (17)

3 (8)

63 (56)

22 (19)

18 (16)

10 (9)

Age in Years: Mean(Range 21-61)

35.6 37.4 -

Employment % (full/part time) - - 66

Mean Education in Years (SD) - - 12.8 (1.7)

Mean Years of Heroin Use (SD) - - 6.6 (8.1)

Present and Clean0001 (Inpatient)

Present and Opiate Clean

Bup/Nx % Clonidine %

N 77 36

Day 3 or 4 52 67.5 16 44.4

Day 7 or 8 63 81.8 13 36.1

Day 10 or 11 56 72.7 10 27.8

Day 13 or 14 59 76.6 8 22.2

Percent Present and Clean0001 (Inpatient)

0

10

20

30

40

50

60

70

80

90

100

Day 3 or 4 Day 7 or 8 Day 10 or 11 Day 13 or 14

ClonidineBup/Nx

Demographics 0002 (Outpatient)Bup/Nx Clonidine Total

Sex No. (%)

Male

Female

115 (73)

42 (27)

51 (69))

23 (31)

166 (72)

65 (28)

Race No. (%)

White

Black

Hispanic

Other

62 (40)

57 (36)

33 (21)

5 (3)

30 (40)

28 (38)

13 (18)

3 (4)

92 (40)

85 (37)

46 (20)

8 (3)

Age in Years: Mean(Range 21-61)

38.3 40.0 -

Employment % (full/part time) - - 56.8

Mean Education in Years (SD) - - 12.4 (2.1)

Mean Years of Heroin Use (SD) - - 9.42 (9.6)

Present and Clean0002 (Outpatient)

Present and Opiate Clean

Bup/Nx % Clonidine %

N 157 74

Day 3 or 4 37 23.6 5 6.8

Day 7 or 8 56 35.7 6 8.1

Day 10 or 11 52 33.1 5 6.8

Day 13 or 14 46 29.3 4 5.4

Percent Present and Clean0002 (Outpatient)

0

5

10

15

20

25

30

35

40

45

50

Day 3 or 4 Day 7 or 8 Day 10 or 11 Day 13 or 14

ClonidineBup/Nx

NNT: Number Needed to TreatCTN 0001 (Inpatient)

• NNT for Bup/Nx 77/59 = 1.31 • NNT for Clonidine 36/8 = 4.5

NNT Clonidine : BupNx = 3.44

CTN 0002 (Outpatient)• NNT for Bup/Nx: 157/46 = 3.4 • NNT for Clonidine: 74/4 = 18.5

NNT Clonidine : Bup/Nx = 5.44

  NNT= Number of patients needed to treat to achieve 1 treatment success

Buprenorphine: what does it really mean?

• The great social experiment: return of opioid addiction treatment to medicine

• Slow progress in implementation: – External barriers: legislative compromises– Inertia and resistance: medication and

recovery

• Application to the world and the region

Pharmacotherapy and Recovery

• Medications and recovery: incompatible?

• “Medication is not recovery”

• The great chemistry paradox– Addiction: chemistry went wrong– Role of “chemistry” (medicine) in recovery

You Can Change the Brain with You Can Change the Brain with Either Biological or Behavioral Either Biological or Behavioral

TreatmentsTreatments

Remember….Remember….

Alan Leshner

How People Change

• “You can change some one’s life by altering his genes; but you can also do that by paying off his credit card”

James Watson

Thanks to

XIII Congress of Psychiatry: symposia organizing committee

National Institute on Drug Abuse

NIDA Clinical Trials Network Staff

CTN Publications Committee

Participating CTN Nodes and CTPs

Reckitt Benckiser: supplier of study med

Participating Patients

You the audience