Amphetamine Addiction in Iceland and efficacy of pharmacotherapy

Report
Amphetamine Addiction in Iceland
and efficacy of pharmacotherapy
Symposium on Emerging Data on Efficacy and Clinical Applications of Extended
Release Naltrexone Formulations, presented at 75th Annual Meeting - College on
Problems of Drug Dependence - June 15-20, 2013, San Diego, CA
Valgerður Rúnarsdóttir, M.D.,
Vogur Hospital Iceland
SAA National Center of Addiction Medicine
Ingunn Hansdóttir, PhD,
Assistant Professor University of Iceland
Research Counsil Member SAA National Center of Addiction
Medicine
1
Disclosure of relevant
financial relationships
• Extended Release Naltrexone for Treating
Amphetamine Dependence in Iceland
• NIDA research grant (2P50-DA012756-11)
• Alkermes provided study drug
Naltrexone/placebo extended release
formulation
2
Investigators
Lead investigators
University of Pennsylvania:
• George Woody, M.D
• Helen Pettinati, PhD
Vogur Hospital:
• Thor Tyrfingsson, M.D.
• Val Runarsdottir, M.D.
Project co-ordinators
• Charlotte Royer-Malvestuto
• Biostatistician:
Kevin Lynch, PhD
• Ingunn Hansdottir, PhD
Data analysis
• Data Manager:
Magnus Einarsson
Other collaborators
NIDA project Manager
Jamie Biswas, MD
Alkermes
Brown University
Avani Desai, PharmD Milunka Kojic, MD
3
Background
• Amphetamine addiction is a growing problem
– Number of patients seeking treatment for amphetamine
addiction has almost tripled over the past two decades
– Proportion of patients has risen, gone from <10% in 1984
to a current rate around 36%
• Amphetamines used intravenously, increased risk of
HIV and Hepatitis
• Increased use among youth
• No medications approved for treating amphetamine
addiction
• Several suggestions that Naltrexone might be effective.
4
Swedish studies
• Jayaram-Lindstrom et al Am.J. Psychiatry, 2008
• Significant effect using oral naltrexone in
ramdomized, placebo-controlled 12 week trial
of 80 amphetmine dependent outpatients.
5
6
Rationale
• Can these results be replicated with extended
release formula?
• Study proposed in Iceland – why Iceland?
7
Icelandic setting
•
•
•
•
•
•
Centralized addiction treatment
Good access to treatment, free or minimal fee
Vogur hospital lynchpin in addiction trmt
Population endorses disease concept
Well trained staff
Evidence based practice
8
Icelandic setting - Treatment as usual:
Detox
• Hospitalization 7-10 days
Residential:
• 4 weeks
Intensive outpatient
• 5x week for 1 mo (60 hrs)
• 1x week for 3 mo (12 hrs)
Outpatient follow-up
• 2x week for 3 mo (24 hrs)
• 1x week for 9 mo (36 hrs)
Detox
7-10 days
Residential
4 weeks
Outpatient
intensive
Outpatient
follow-up
9
Study Design -I
• 100 amphetamine dependent treatment seeking
patients at Vogur Hospital
• Randomized, double blind trial and 6 month trmt
with VIVITROL® or VIVITROL®placebo and
Treatment as usual
• Stratified by gender and IV status.
• All participants detoxed at Vogur Hospital and
consented.
• Randomized before going to outpatient status.
10
Study Design-II
Detox
baseline
N=100
First study injection
First study injection
Intensive
Outpatient
N=39
Residential
treatment
N=61
Treatment
n=23
Treatment
n=28
Placebo
n=16
Placebo
n=33
11
Screening and randomization
169 assessed for eligibility
69 excluded
27 did not complete detox
7 refused participation
7 did not start trmt
28 other reasons
100
Randomized
51 assigned to receive Vivitrol
49 assigned to receive placebo
11 lost to follow-up
7 lost to follow-up
10 completed
assessments
13 completed
assessment
6 withdrew consent
4 withdrew consent
24 completed study
25 completed study
12
Study design - III
Wk 1
Wk 8
Wk 4
Wk 24
Wk 16
Wk 12
Wk 20
• Repeat injections weeks 4, 8, 12, 16, 20
• Baseline assessments:
Medical & social history, liver panel (wk3, 11, 23), HepC
& HIV (wk24), ASI (wk 12, 24), Fagerström (wk 12, 24)
RAB (wk 24), AUDIT (wk 24), Blood for genetics
• Brief weekly assessments
urine, alcohol breath, AE‘s, TLFB, TSR, Craving
• Monthly assessments
relapse, pregnancy, BDI, EuroQol,
• Month 12, mail-in assessment
13
Study Design- outcomes
Primary outcome
• Proportion of amphetamine negative urines
during weeks 1-24 of outpatient treatment
Secondary outcomes
Time to relapse
HIV risk behavior
Treatment retention
Amphetamine craving
Drug use
Criminal activity
Depression
Quality of Life
14
Inclusion criteria
• Aged 18 or above.
• Primary diagnosis of current amphetamine
dependence as defined by DSM-IV-TR with
=>10 days of amphetamine use in past month.
• Successfully complete 7-10 day assessment and
study baseline measures at Vogur.
• Abstinent from substances for at least 7 days
• Provision of contacts of 3 people
• Written consent
15
Exclusion criteria
• AST or ALT >5 times the top limit of normal.
• Physiologically dependent on opioids or other
substances (nicotine excepted) or known
concomitant or planned use of opioid
analgesics, positive opioid urine drug test or
positive naloxone challenge,
• No severe psychiatric, cognitive, or medical
problems and no known hypersensitivity to
naltrexone
16
Sample characteristics
• No significant differences between treatment
grps on sample characteristics.
• Males
75%
• Caucasian
100%
• Average age 31 years
– (19-30 years 49%; 30-40 36%; 40-58 15%)
• IV injecting
• HIV +
• HEP C
20
0
9
17
Baseline demographics
• No significant differences between treatment grps on
baseline demographics.
• Stable housing
• Never married
• Living with partner (>1year)
88%
37%
14%
• Education completed 10th grade
59%
• Not completed 13%
• Employment (>11 days past mo)
12%
18
Baseline diagnosis
DSM-IV checklist
physician diagnosis
Amphetamine dependence
Alcohol dependence
Cannabis dependence
Cocaine dependence
Methylphenidate dependence
Sedative dependence
Opiate dependence
N (%)
100
75
69
26
15
30
0
19
Baseline
Placebo Treatment
(N = 49) (N = 51)
•
•
•
•
•
Prior admissions, mean #
BDI score
RAB drug risk
RAB sex risk
Amphetamine craving
3
13
0.8
5.2
47
3
14
1.5
5.7
41
(VAS 0-100)
20
Self-reported amphetamine use 4
weeks prior to study
TLFB
Amphetamine use past month
Methylphenidate use past motnh
Craving – VAS
mean
18 days
0,6
44 (0-100)
No difference at baseline between trmt grps
21
Missing data and retention
• 53% of treatment grp provided UDS at wk 24
• 47% of placebo grp provided UDS at wk 24
• No differences in distributions of time to drop
out between the trmt grps (log-rank test)
22
Retention
Number of subjects receiving study treatment
100
100
Four or more injections:
22 treatment (29<4)
28 placebo (21<4)
90
80
72
70
60
50
40
56
47
Total
46
37
Treatment
Placebo
30
20
10
0
injection 1 injection 2 injection 3 injection 4 injection 5 injection 6
23
Negative urines;%
1247 urines collected (1194-/53+) 2400 urines target
100%
90%
80%
Observed
Treatment
70%
60%
Observed
Placebo
50%
40%
Imputed
Treatment
30%
Imputed
Placebo
20%
10%
0%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
% Drug Positive Urines
(N=1257)
•
•
•
•
•
Amphetamine:
Benzodiazepines:
Marijuana:
Cocaine:
Opioids:
4.25
8.26
6.98
1.44
0.96
25
Ampetamine Craving Scale by trmt grp
Treatment Placebo
50
45
Amphetamine craving score
40
35
30
25
20
15
10
5
0
1
2
3
4
5
6
7
8
9
10
11
12
13
Weeks 0-24
14
15
16
17
18
19
20
21
22
23
24
Relapse
• 29 subjects self-reported amphetamine
relapse (3 days or more) over 6 months
– Treatment group: 14
– Placebo group:
15
• 32 subjects self-reported alcohol
relapse (3 days or more) over 6 months
– Treatment group: 19
– Placebo group:
13
27
SAE
•
•
•
•
•
15 participants had a SAE with 20 events
17 hospitalization due to relapse
1 pneumothorax
1 abdominal pain, elevated liver enzymes
1 potential suicide attempt with relapse
28
AE severity
mild, moderate, severe
Treatment
Severe; 5%
Treatment
Total AE reports 188
Placebo
Total AE reports 194
Placebo Severe 2%
Placebo
Moderate 16%
Treatment
Moderate 28%
Treatment
Mild 67%
Placebo Mild 82%
Adverse Events (total)
64 subjects reported an adverse event
38 subjects reported pain/swelling injection
site
30
Secondary outcomes
Placebo Placebo Treatm Treatm
BSL
W24
BSL
W24
BDI score
RAB drug risk
RAB sex risk
Amphetamine
craving
n=49
n=28
n=51
n=24
14.8
0.8
5.2
47
8
0.15
4.5
16
15
1.5
5.7
41
6
1.0
4.0
12
31
Conclusions
• Robust response to treatment as usual for those
who stayed in trmt with no additional benefit
from Naltrexone.
• Results did not replicate previous findings
• Similarties to other studies: in regards to severity
of dependence BSL and retention
• Difference in amount of treatment received, start
off in detox and 61% residential trmt before
getting study drug.
• Trend towards worse outcome for those going
directly to outpatient (37% /56% +UDS res/out)
32
Thanks for your attention
• Thank you!
33

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