1. AGONIST/PARTIAL AGONIST Heroin: DSM IV THE SIREN EFFECT (HOMER & THE ODYSSEY)

2. ORAL NALTREXONE  Good pharmacological efficacy  Poor Compliance

4. Pharmacotherapy Works  PHARMACOTHERAPY WORKS But only if you actually get the right medication the right medication into the right patient most of the time

6. DEPOT NALTREXONE Therapeutic naltrexone blood levels above 1-2 ng/ml suggested Remove onus for oral compliance Objective: facilitate stable opiate-based abstinent lifestyle Available Depot Preparations 4-6 weeks Biotek, Inc. (Depotrex®) {Comer, 2002}; Drug Abuse Sciences (Naltrel®) {Kranzler, 2004}; Alkermes, Inc. (Vivitrol®) {Garbutt, 2005} FDA Approved

7. Randomised (70 DSM IV Heroin Dependent Persons) double-blind placebo controlled clinical trial compared to oral naltrexone Hulse, GK; Tait, RJ; Ngo, HT; Morris N; Arnold-Reed D Funded: National Health & Medical Research Council

9. Belt line V shaped insertion lateral to the iliac crest

10. Clinical Efficacy  Survival –– return to regular (most days / daily) heroin use  Patterns of heroin use –cumulative

11. Implant v Oral (compliant) Relationship Between:  Blood Naltrexone levels  Craving  Return to opioid use

12. ADVERSE AND SERIOUS ADVERSE EVENTS

13. Return to regular (most days/daily) heroin use

14. Return to regular (most days/daily) heroin use versus > 1-3 times / month

15. Return to regular (most days/daily) heroin use or lost to follow-up Hulse, G.K., Morris, N., Arnold-Reed, D., Tait R.J. (2009). Treating heroin dependence: Randomised Trial of oral or implant naltrexone. Archives of General Psychiatry Manuscript 66(10): 1-8 (impact factor 14.2)

16. Cumulative (worst) heroin use outcomes over the study NB 4 lost to follow-up 5 new treatment NB 4 lost to follow-up 2 new treatment

17. 1.Blood Naltrexone 2.CRAVING 3. HEROIN USE INTERRELATIONSHIP

18. Findings from Challenge studies:  2.8ng/ml blocks 500mg of diamorphine (Brewer 2002)  ≥ 2ng/ml blocks 25mg IV heroin (Navaratnam, 1994, Verebey, 1976)  1 ng/ml blocks15mg morphine (Chiang, 1985) Identifying the Therapeutic Blood Naltrexone Level for the Management of Heroin Dependence

19. NALTREXONE BLOOD LEVEL RISK FOR ≥ WEEKLY HEROIN USE  2.5 risk below 0.5 ng/ml  Each 1ng/ml increase = 35% decrease risk heroin use  Above 3ng/ml can be confident of absence or low level use Data Suggest: Minimum Therapeutic Blood Naltrexone level =1ng/ml No need to exceed 3ng/ml

20. IMPLANT COMPARED TO COMPLIANT ORAL NALTREXONE

21. INCREASED RISK ≥ WEEKLY HEROIN USE  NON COMPLIANT ORAL THAN ALL OTHERS  GREATER IN COMPLIANT ORAL THAN IMPLANT

22. Heroin Craving Craving assessed with 10 item survey scale scored 1 to 7 (Tiffany, 1993)  Implant significantly lower craving at month 5  Overall, implant show less craving than oral Naltrexone

23. IMPLANT COMPARED TO COMPLIANT ORAL NALTREXONE

24. CRAVING ASSERSSED MONTHLY IMPANT & COMPLIANT ORAL HAD LOW CRAVING NON COMPLIANT ORAL HAD INCREASED CRAVING

25. OTHER STUDY CRAVING PREDICTORS i.High craving at baseline ii.Increased years of heroin use iii.Being Female iv.Being Younger Older Persons Have Lower Craving

26. ? Clinically: why is craving so important?

27. CRAVING  Previous month craving Predictor of subsequent heroin use

28. Study Adverse & Serious Adverse Events Independent monitoring Committee: Professor of Psychiatry, Professor of Public Health, Two Addiction Specialists (Fellows of the Australasian College of Addiction Medicine) Events were classified as: "unexpected" (but probably related to the device/procedure), "expected" (and probably related to the device/procedure), "pre-existing" (i.e. present at the time of enrolment), or "unrelated". TGA guidelines based on International Conference on Harmonization policies.

29. TreatmentCategoryDaysSummary ImplantRelated expected0Wound hematoma - bleeding, swelling, pain proximal to implant site ImplantPre-existing108Psychotic episode ImplantPre-existing110Substance abuse (‘alcoholic binge’) ImplantPre-existing128Psychosis ImplantPre-existing131Suicide attempt ImplantPre-existing141Depression ImplantUnrelated0Bradycardia and collapse – allergic reaction to clonidine ImplantUnrelated28Drug overdose (Risperadone) requiring hospital admission ImplantUnrelated35Abscess on neck ImplantUnrelated161Miscarriage (septic abortion) at 7 weeks gestation TabletPre-existing0patient had commenced opioid withdrawal days prior to presentation TabletPre-existing6Depression and suicide ideation TabletUnrelated19Possible spinal nerve damage referred right leg and ankle TabletUnrelated56Poly drug overdose (Buprenorphine, Serepax) hospital admission † TabletUnrelated61Poly drug overdose (Buprenorphine, Serepax) hospital admission † TabletUnrelated84Pneumonia (left basal) and pleurisy Summaries of all the serious adverse events

30. Classification of Implant Reaction Three Dimensions REDNESS, SWELLING and TENDERNESS. Each rated on a 4-point scale ZERO(no reaction) to THREE (severe).

34. THANKYOU