Issues around Naltrexone
Implants
Dr Lucy Cockayne
Consultant Addiction Psychiatrist.
Maintenance with antagonists?
“the great disproportion seen in favour
of programmes with agonists… is not
actually due to major advantages with
the former but rather to… limitations of
the latter”
treatment should be in the “least
restrictive context possible”
Heroin Addiction
The UNODC estimated that in 2001 over
15million people globally were using heroin.
Opioid drug addiction affects over 250 000
people in the UK.
Heroin use poses the greatest threat to the
health of drug misusers compared to other illicit substances, with 790 mentions on
Current Treatment for Heroin
Users
Methadone and subutex maintenance
therapy the standard treatments.
Drawbacks include:
High drop-out rate
Indefinite duration of treatment Most users continue to use illegal
substances
Naltrexone
Currently available on NHS as oral
treatment.
Opiate antagonist: blocks µ receptors.
“Therapeutic” blood levels of 2ng/ml
override high dose diamorphine.
Shown to be successful in treating
highly motivated patients (Washton,
1984).
Problems with oral naltrexone
Washout period required before initiation
of treatment.
Treatment must last at least 12 months.
Compliance is poor due to:
Possible adverse effects e.g.dysphoria Absence of opiate induced reinforcement
Enhancing naltrexone compliance –
do we try hard enough?
Entrusting administration to a
relative or carer (Anton, 1981)
Contingency contracting (Preston,
1999)
Naltrexone administered by
probation officers (Chan 1996,
Cornish, 1997)
Chan and Cornish studies
Chan, Singapore
Jail release programme Highly structured
NTX 100:100:150 weekly
75% c.w. 25% opiate free at 12 months
Cornish, USA
NTX twice weekly 100:150
Halves re-incarceration rates, reduced positive
First do no harm?
Is there increased risk of fatal overdose?
“findings do not support the hypotheses that
prior exposure to naltrexone increases
sensitivity to heroin toxicity”
Arnold-Reed 2003
overdose fatalities more likely after periods of
abstinence or reduced use of opiates
through a lowering of tolerance
opiate antagonists MAY exaccerbate this
NTX exposed and non-NTX exposed fatal
heroin overdoses
Arnold-Reed 2003
Methods
Reviewed toxicology reports 97-99 Compared 21 NTX with 71 non NTX
Results
No difference in proportion of deaths related to
heroin
Blood total morphine levels NOT less
“New” on the market
1. 2 implants:
1. Marlburg, “Wedgewood” 1G NTX average
blockade 6 -7 weeks
2. O’Neil, “Go-medical” more sophisticated last up
to 12 months depending on number of implants inserted (single 1.7g, double 3.4g, triple 5.1g)
Single maintains blood level above 2ng/ml for 80 days. Double 165+ days.
Implantation Procedure
Lower abdomen locally anaesthetised
with Xylocaine 2%.
Using aseptic techniques a 3-5cm
abdominal incision will be made.
An initial 6 week implant will be
inserted.
Incision will be sutured up with 2 or 3
stitches which are removed after 7
days.
Implantation Procedure cont…
Patients are given prophylactic
flucloxacillin and cephalexin (5 days).
Volunteers are reassessed 7-14 days
later.
Subsequent implants will last 10 and
then 12 months and be inserted on
alternate sides of the abdomen.
Known use of implants
Western australia 582 patients with Go
Medical implants since 2000 (Hulse 2003)
Use in private sector in UK and USA
USA deaths associated with NIMROD
Use in NHS setting in England
Sheffield GP
Some Stapleford clinic patients NHS funded NW GP over 150 implants
Potential problems with
implants
Psychological
“wonder cure”
coping with being drug free taking away freedom of choice
Physical
implant site – reactions
“rare” Carreno et al 2003
trying to over-ride implant
WHAT IT IS
WHAT IT IS
NOT
NOT
A WONDER CURE
A CHEMICAL STRAIT JACKET
What it CAN do
Provide respite from opiate use
give the opportunity for other
interventions to work
act as a “response prevention” measure
Maintenance Treatment?
Carreno et al 2003
156 patients on naltrexone implants for 12
months
Retention 80% at 6 months, 65 at 12 Retention 55.4 at 18 months 20.8 at 24
High risk adolescents
Hulse 2003, Australia
8 adolescents with multiple overdoses
requiring hospital treatmentwho had tried oral NTX
Retrospective comparison pre and post
implant
Small reduction in overdose with oral NTX “dramatic reduction…. ass w. implant”
Prevention of relapse
Foster et al 2003
101 British patient in 2 cohorts 6 week implant
86 - 89% opiate free at 12 weeks
30% tested out implant in first week
Typical blood levels 3-5ng/ml at week 4,
Kenyon House pilot study – take
home messages
Surgical procedure requires suitable set
up, skills and continuity of follow up
Preferable to be provided by local
services
Reductions in MAP scores and opiate
use promising
No “swapping” of addiction
Client demand demonstrated
Where will implants be particularly
helpful? For debate………
Young starters - where emotional
development has been blocked by
addiction
experienced users who have had
multiple detoxes
Proposed Study Designs
Small randomised controlled trials at single
sites : Dr Carnwath and Scottish equivalent
Naturalistic study of larger group, possibly
Research Questions
What is the effect of two years of opiate receptor
blockade on opiate seeking behaviour and opiate addiction, both during and for one year after
treatment?
How does patient compliance to naltrexone
implant treatment compare with oral naltrexone therapy?
What are and how frequent are adverse reactions
to naltrexone implants (allergic reactions, local infections, liver dysfunction etc.)?
Research Questions cont…
How do patients subjectively rate their
experience of naltrexone implants in
comparison to other treatments they
have received?
Is treatment with naltrexone implants
cost-effective and feasible in a publicly
funded setting?
Cost Analysis – Oral
naltrexone
24 months supply of oral naltrexone
= £1020.24
Liver Function tests (£10 x 13)
= £ 130.00
Urinary Drug Screen test (£7 x 13)=£ 91.00
Pregnancy test (£4 x 13 per female)= £52.00
Naltrexone plasma levels (£ x 12)= £ n/k
Cost Analysis – Per Implant Pt
1 x 6wk naltrexone implant = £125.00 2 x 12month naltrexone implant = £1800.00 1 week supply of oral naltrexone= £10.63 2 courses flucloxacillin = £6.76 2 courses cephalexin = £3.33 Xylocaine 2% (x 3) = £1.95 Iodine (Betadine) Solution = £1.75
Cost per Implant pt cont…
Liver Function tests (£10 x 13) = £130.00 Urinary Drug Screen test (£7 x 13) = £91.00 Pregnancy test (£4 x 13 per female)= £52.00 Naltrexone plasma levels (£ x 12) = £ n/k
References
Report of the Office on Drugs and Crime of the United
Nations Secretariat – United Nations Economic and Social Council, March 2004.
Ward J, Mattick R, Hall W – Methadone Maintenance
Treatment and Other Opioid Replacement Therapies. 1998, Harwood Academic Publishers.
Washton A M, Pottash A C, Gold M S – Naltrexone in
Addicted Business Executives and Physicians. Journal of Clinical Psychiatry 1984; 45:4-6
Kirchmayer U, Davoli M, Verster A – Naltrexone
Maintenance Treatment for Opioid Dependence (Cochrane Review). In: The Cochrane Library Issue 1, 2004.
References cont…
Anton R E, Hogan I, Jalali B, Riordan C E, Kleber H D – Multiple
Family Therapy and Naltrexone in the Treatment of Opiate Dependence. Drug & Alcohol Dependence, 1981; 8 : 157-68
Preston K L, Silverman K, Umbricht A et al – Improvement in
naltrexone treatment compliance with contingency management. Drug & Alcohol Dependence 1999; 54 :127-135
Cornish J W, Metzger D, Woody G et al – Naltrexone
Pharmacotherapy for Opioid Dependent Federal Probationers. Journal of Substance Abuse, 1997; 14: 529-534
Gessner P, Gessner T – Disulfiram and its metabolite
Diethyldithiocarbamate. 1992, Chapman & Hall, London. p245
Comer S D, Collins E D, Kleber H D et al – Depot Naltrexone: Long
Lasting Antagonism of the Effects of Heroin in Humans. Psychopharmacology 2002: 159: 351-360
