Transcript Ross Colquhoun - GP Laboratories Ltd

10th Stapleford
International Addiction
Conference
Long Acting Chinese NTX
Implant Trial D H Sc, M AppRossSc,Colquhoun
B Sc Hons
Addiction Treatment and Psychology Services
67 Macarthur St, Ultimo NSW 2007
Phone Number: (612) 9280 2070
Email: [email protected]
www.addictiontreatment.com.au
Introduction
 Since early 2000, naltrexone implants have been
manufactured or imported and used in Australia.
 Naltrexone (NTX) implants, especially long-acting
ones, seem to offer a solution to the problem of
compliance with oral NTX and may appear to improve
long-term outcomes.
 Most available implants are still unregistered and
unlicensed and concerns have been raised about their
pharmacokinetics, safety and effectiveness.
Introduction
 The present trial was designed to test the serum blood
levels of naltrexone (NTX) and 6-β-naltrexol (NTL)
over the 6 mths of the claimed effectiveness of the
“Chinese” naltrexone implant manufactured by
Shenzhen Civil Life Scientific of Shenzhen, China
 Serum blood levels were compared to other outcomes
of interest including drug use, changes in liver
function and social functioning
Naltrexone Treatment and
Implants- Context
 Naltrexone is non-toxic, non-addictive and with few
and no serious side-effects
 Naltrexone has never caused anyone to die
 Naltrexone does not cause depression
 Naltrexone was never a ‘miracle cure’.
 Good outcomes can be achieved using Naltrexone
Implants combined with counselling
 It is a valuable adjunct to treatment. Addicts know
this; so do experts
Naltrexone Treatment and
Implants- Context
 Three stage treatment program for Methadone and
Heroin Treatment
1. Assessment and Pre-detox Counselling and Preparation
– family involvement
2. Detoxification - Rapid One-day, Accelerated and Home
Detoxification
3. Aftercare Counselling and Structured Rehabilitation,
Naltrexone Implant
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Psychological and Medical Assessment
Inclusion of Families
Pre-detox Counselling and Preparation
Treatment Planning
Naltrexone Treatment and
Implants- Context
 The form of detoxification does not predict long-term
outcomes (Colquhoun, 1999; Currie, 1999) only the
number who complete the process and therefore, the
number who are able to commence the after-care
program.
 After-care protocol of implant naltrexone, 6 months outpatient counselling and family support is recommended
 Far superior results to traditional after-care programs,
including in-patient rehabs.
Naltrexone Treatment and
Implants - Context
 Provide blockage of opiates for 6 to 10 months
 Readily re-inserted for much longer protection.
 Very cost effective compared to long-term
maintenance.
 Ideally suited for
 stable methadone patients
 motivated heroin addicts who have invested much in
getting clean
 chronic pain patients dependent on opiates
 Unsupported addicts, eg leaving jail
Naltrexone Treatment and
Implants - Context
 Oral vs Implant Naltrexone Study*
 Concord Seminar Series 2010**
*Colquhoun, R. M., Tan, D. Y. K & Hull, S. (2005). Comparison of oral and
implant naltrexone at 12 months. Journal of Opioid Management, 1(5),
pp. 426-439.
**Colquhoun, R. M. Paper delivered at the Concord Hospital D&A
Seminar Series, 2010
Oral vs Implant Naltrexone Study
 42 oral ntx, 41 implant ntx.
 Assessments pre-detox found the groups were
comparable in terms of sex (63% male), age (mean
28yrs approx) years using opiates (mean 8yrs approx),
and psychopathology (BDI-II and SCL-90-R)
 Patients and their support persons were routinely
contacted via telephone for a period of around 6
months, and compared on a number of outcomes.
Oral vs Implant Naltrexone Study
 Based on the reports of patients and their support
persons at the end of 6 months, it was found that 17 of
the 42 people in the oral group had relapsed (60%
abstinent). By 12 months 25 had relapsed (41% abst),
including 8 who could not be contacted
 Only 8 of the 41 people in the implant group were
regularly using opiates at 6 months (80% abst), while
at 12 months 16 had relapsed (60% abst), including
another 8 people who could not be contacted.
Oral vs Implant Naltrexone Study
 At the end of the follow-up period, patients
gave a rating of self-esteem and general
relationship quality both before detox and at
present on a 0-10 scale (0 = disastrous, 10 =
excellent).
 The means for the two groups were found to
indicate significant improvement in social
outcomes as measured by self reports of selfesteem and quality of closest relationships
Oral vs Implant Naltrexone Study
Self-esteem and general relationship quality pre-detox and 12months post-detox, compared for oral and implant naltrexone
groups (means reported)
SE pre
detox
SE post
detox
RQ pre
detox
RQ post
detox
Oral group
3.8
8.3
2.2
8.8
Implant
group
3.9
8.7
2.4
8.1
Concord Seminar Series 2010
Treatments: 295 patients treated in 2009#
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
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

Gender: 178 (60.2%) males; 117 females
Mean age: 30.33 yrs
Age commenced opiates: 20.8 years old
Mean Years Using: 8.9
Mean score on SCL-90-R GSI scale at start of program: 74.5
Mean score on SCL-90-R GSI scale at 6 months: 47
# Study and counselling program funded by Commonwealth Dept of Health
and Ageing and Attorney Generals Dept (Proceeds of Crime)
Concord Seminar Series 2010
Naltrexone Implants
Of 295 patients 177 ROD (60%)
 118 did not a have ROD: 78 Home or in-patient detox






(66%); 61 second or more implant
Implants: 275 (93%); Oral Ntx; 20
Poly Drug in the past: 258 (87.5%)
Poly Drug use at time of entering program: 112 (38%)
Heroin: 177 (60%), Methadone: 77 (26%) (heroin/meth
12%); Bup: 18 (6%) (her/bup 3%); Morphine: 12 (4%); 18
Alc: 6% (implants)
Tissue reactions : 21 (7.6%)
Extrusions: 5 (1.8%)
Concord Seminar Series 2010
Adverse Events Related to Implants
 Specific problems related to implants (only 1 out of 12
reported had implant related adverse evetns -local
infection/abscess in Lintzeros Report*)
 Rates of infection (very rare); more often
inflammatory tissue reaction comparable to the use of
testosterone implants**
 Rapid detoxification, and naltrexone implants to
prevent early relapse, are two different phases of
treatment.
*Lintzeros, N., Lee,S., Scopelliti, L., Mabbutt, J. and Haber, P. S. Unplanned Admissions
toTwo Sydney Public Hospitals after Naltrexone Implants, Medical Journal of Australia,
Vol 188 (8) 441-444
**Handelsman, D. J., Mackey, M., Howe, C., Turner l. and Conway, A. J. An analysis of
testosterone implants for androgren replacement therapy. Clinical Endocrinolgoy, Vol
47(30), Sept 1997, 311-316
Concord Seminar Series 2010
Adverse Events Related to Implants
 Infection:
 Remedy
 Use of antibiotics
 Rejection:
 Remedy
 Use of steroid anti-inflammatories (Prednisone)
 Very often mistaken for infection
 Fibrotic Encapsualtion:
 Remedy
 Surgical removal of tissue
Concord Seminar Series 2010
Adverse Events Related to Implants
 Overdose:
 Nearly impossible while the implant is active
 Remedy
 Warn about reduction in tolerance to opiates and possibility of overdose
even with greatly reduced amounts when implant blocking effect ceases
 Very rare – similar rates to those leaving jail or rehabs – good reason to
have an implant when leaving jail
 Analgesia:
 Use of other medications and pain management strategies
 Use of non-opoid analgesics
 Hyperalgesic effects in chronic pain patients
Long Acting Civil Life NTX
Implant Trial
 41 participants who had been implanted after
detoxification in Sydney as at 23 Feb 2011.
 Mean age 29.56 years,
 92% male
 60% employed full-time
 95% using heroin
 Mean 9.6 years using
 60% drug related convictions
 17 tests completed at one month, 10 at three months, 4
at six months
Long Acting Civil Life NTX
Implant Trial
Mean self ratings of self-esteem and general relationship
quality pre-detox and at 1 and 3 months post-detox (range)
Self Esteem
Relationships
Pre-detox
3.36 (2-5)
5.1 (0-10)
One months
7.25 (4-10)
9.2 (7-10)
Three months
6 (4-8)
9.5 (9-10)
Long Acting Civil Life NTX
Implant Trial
 Mean self rating of craving while using, during
detoxification and 1 month post implant (range)
Craving while
Using
Craving during
detox
Craving at 1
month post
implant
5.8 (3-10)
7.36 (5-10)
0.81 (0-6)
Long Acting Civil Life NTX
Implant Trial
 Mean Liver Function Index pre-implant and one
month post implant (range)
LFI Pre-implant LFI one month
Post-implant
T-test
0.66 (o.365-1.202) 0.69 (.45- 0.895)
P= 0.78 non sign
Serum Blood Levels at 1 month
Days









55
26
48
49
55
53
29
26
31
Ntx
Ntl
6.1
5.9
9.1
4.6
6.6
3.7
3.9
12.1
19.5
7.9
6.3
9.1
5.9
6.6
3.3
6.4
9.1
21.3
Serum Blood Levels at 1 month (cont)
Days
36
 38
 33
 42
 29
 29
 30
 30
 Mean 37.58
 STD 12.31

Ntx
Ntl
5.9
2.5
0
10.1
5.4
13.2
6.1
8
7.22
4.72
6.7
2.7
9.6
9
7.8
25.1
7.9
10.4
9.12
5.74
Serum Blood Levels at 3 months
Days
 80
 102
 99
 88
 70
 80
 66
 70
 68
 53
 Mean 77.6
 STD 27.48

Ntx
4.6
4.6
9.1
0
6.1
0
5.9
0
3.9
2.5
3.67
1.81
Ntl
6.5
6.9
9.1
5.1
6.5
4.3
6.7
6.2
6.4
2.7
6.04
1.45
Serum Blood Levels at 6 months
Days
 212
 170
 222
Mean 201.3
STD 101.69

Ntx
0
0
0
0
0
Ntl
0
6.6
0
2.2
3.14
NTX Blood Serum levels ng/ml
25
20
15
Series1
10
5
0
0
50
100
150
200
250
NTL Blood Serum levels ng/ml
40
35
30
25
20
Series1
15
10
5
0
0
50
100
150
200
250
Blood serum levels at 1 month
and LD enzyme levels
AC
HN
MN
SC
MB
DA
BB
NTX
2.5
3.9
4.4
3.7
10.1
12.1
6.1
NTL
2.7
6.4
5.9
3.3
9.0
9.1
6.5
LD Pre
137
174
167
172
176
136
156
LD Post
293
462
278
421
270
527
323
Discussion
 Of the 41 subjects who started the trial only 31 samples
had been analysed to date. Of these four had tried
using heroin in the first month and all reported that
there was no subjective effect.
 One started using heroin at 5 months, but reported
little effect, but some withdrawal. He has returned to
being abstinent and has continued counselling
 One subject relapsed to heavy cocaine use after one
month, his implant extruded and he relapsed.
 Another whose implant extruded after 3 months
relapsed to heroin
Discussion
 There were five tissue reactions and three implants
extruded (12% and 7% resp)
 Much higher level compared to the earlier Concord
study of 275 patients (7.6% and 1.8%)
 Management with Cortosteroids recommended
 While changes in Liver Function were not significant it
was noted that LD levels became markedly elevated in
7 patients. Ethics committee notified and patients
being monitored. – early indications show reduction in
liver enzyme levels at 3 months
Discussion
 Research has consistently shown that:
 ROD under sedation is a highly effective form of
detoxification from heroin and is cost effective;
 it is probably more cost effective than methadone;
 Slow methadone reduction has a 20% completion rate
at 6 moths at an average cost of $100,000 per patient*
 ROD has a 100% completion rate and 80% abstinence
rate at $8100 per patient when combined with an
implant
 Other factors effecting long-term outcomes include:
 Positive therapeutic relationship, counselling and
monitoring of medication compliance (World Health
Organisation, 2004).
*Roberts, L. MTAR Research, APSAD Conference 2006
Acknowledgement
 Shenzhen Civil Life Scientific Co and Dr
Wayne Moran– supply of naltrexone
implants for the trial
 www.ntximp.com
 Royal Prince Alfred Hospital, Chemistry
Laboratory, Sydney analysing blood serum
levels
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presented at New Horizons: Reducing Drug Harm in the New Millennium, Alcohol and Drug
Foundation (Qld), Brisbane.
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273-280.
Currie, J., Collins, L., Mudaliar, Y., Cox, P., Guant, L., Lutz, P., & Ward, H. (1999). Rapid induction
onto naltrexone: A randomised clinical trial of anaesthesia-assisted and sedation-assisted techniques
and a comparison with conventional detoxification. Presented at the Western Area Health Service,
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efficacy of naltrexone in preventing re-abuse of heroin after detoxification. Biological Psychiatry, 35,
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the art. Journal of Addictive Diseases, 16, pp. 103 – 121.
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Washton, A.M., Pottash, A.C., & Gold, M.S. (1984). Naltrexone in addicted business executives and
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Geneva: World Health Organisation Library.