Issues around Naltrexone Implants

Transcription

1 Issues around Naltrexone Implants Dr Lucy Cockayne Consultant Addiction Psychiatrist. Lanarkshire Primary Care Trust

2 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 Carreno 2003

3 Heroin Addiction The UNODC estimated that in 2001 over 15million people globally were using heroin. Opioid drug addiction affects over 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 death certificates in 2002 (ONS, 2004)

4 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 unattractive to some GPs and users

5 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).

6 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 No adverse effects on treatment withdrawal

7 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)

8 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 urines

9 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 White 99, Darke 2000, Seaman 98

10 NTX exposed and non-ntx exposed fatal heroin overdoses Arnold-Reed 2003 Methods Reviewed toxicology reports Compared 21 NTX with 71 non NTX Results No difference in proportion of deaths related to heroin Blood total morphine levels NOT less Possible increased risk of rapid death - NS

11 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. 2. BUT device NOT licensed for human use

12 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.

13 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.

14 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 DNW pilot study

15 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 30% test out in first week Carreno et al 2003

16 WHAT IT IS NOT A WONDER CURE A CHEMICAL STRAIT JACKET A TOOL FOR ENFORCEMENT

17 What it CAN do Provide respite from opiate use give the opportunity for other interventions to work act as a response prevention measure to allow alternate coping strategies

18 Maintenance Treatment? Carreno et al 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 All opiate free

19 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

20 Prevention of relapse Foster et al 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, blockin up to 500mg diamorphine

21 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

22 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 early intervention to prevent escalation

23 Proposed Study Designs Small randomised controlled trials at single sites : Dr Carnwath and Scottish equivalent Naturalistic study of larger group, possibly with a matched control group

24 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.)?

25 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?

26 Cost Analysis Oral naltrexone 24 months supply of oral naltrexone = Liver Function tests ( 10 x 13) = Urinary Drug Screen test ( 7 x 13)= Pregnancy test ( 4 x 13 per female)= Naltrexone plasma levels ( x 12)= n/k TOTAL :

27 Cost Analysis Per Implant Pt 1 x 6wk naltrexone implant = x 12month naltrexone implant = week supply of oral naltrexone= courses flucloxacillin = courses cephalexin = 3.33 Xylocaine 2% (x 3) = 1.95 Iodine (Betadine) Solution = 1.75

28 Cost per Implant pt cont Liver Function tests ( 10 x 13) = Urinary Drug Screen test ( 7 x 13) = Pregnancy test ( 4 x 13 per female)= Naltrexone plasma levels ( x 12) = n/k TOTAL COST =

29 References Report of the Office on Drugs and Crime of the United Nations Secretariat United Nations Economic and Social Council, March 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, Chichester, UK : John Wiley & Sons Ltd.

30 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 : Preston K L, Silverman K, Umbricht A et al Improvement in naltrexone treatment compliance with contingency management. Drug & Alcohol Dependence 1999; 54 : Cornish J W, Metzger D, Woody G et al Naltrexone Pharmacotherapy for Opioid Dependent Federal Probationers. Journal of Substance Abuse, 1997; 14: 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: