Buprenorphine and the NIDA CTN: Research to Practice
Walter Ling & Richard Rawson ISAP/UCLA
XIII World Congress of PsychiatrySeptember 14, 2005
Cairo, Egypt
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