Opiate Dependency bka Opioid Addiction

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Opiate Dependency bka Opioid Addiction GP CME Dunedin July 2012 Doug Sellman Professor of Psychiatry and Addiction Medicine Director, National Addiction Centre University of Otago, Christchurch

What this talk is about Therapeutic communities No Ibogaine or other entheogenic treatment No Opioid substitution treatment Yes - objectives of OST - brief history - waiting lists and interim prescribing - buprenorphine - oxycodone - primary care taking a primary role in OST

OST Objectives Clinical practice guidelines (2008) Contribute to the health, psychological and social functioning and wellbeing of clients/tangata whai ora and their families Reduce the spread of infectious diseases associated with injecting drug use, especially hepatitis B and C and HIV/AIDS Reduce the mortality and morbidity resulting from the misuse of opioid drugs Assist individuals to achieve a successful withdrawal from opioids Reduce episodes of other harmful drug use Reduce crime associated with opioid use Assist with recovery from opioid dependence and withdrawal from methadone, or other opioid substitute medicine, if appropriate and desired by the client/tangata whaiora.

Dr Vincent Dole (1913-2006) Dr Marie Nyswander (1919-1986)

Dole & Nyswander Model (1964/65) Metabolic disorder like diabetes Blockade dose of methadone to prevent narcotic hunger, typically 80 120mg A comprehensive, individualised programme of rehabilitation Prescription for as long as the patient is benefiting

New Zealand pioneers Dr Fraser MacDonald Auckland Dr John Dobson Christchurch Dr Derry Seddon Tauranga Mr John Hannifin Palmerston North - First methadone conference 1979 - National Protocol 1992

New Zealand issues: first 20 years Opioid dependence: a disorder of the endogenous opioid system Methadone for opioid dependence in conflict with the abstinence model - its like giving gin to alcoholics HIV/AIDS: more life threatening than opioid dependence Opioid dependence and co-morbidity Determining an optimal dose of methadone (Sellman, Deering, Robinson 1995)

Methadone maintenance treatment: Coming of age in New Zealand - Stabilisation, Rehabilitation, Community Reintegration, Withdrawal - Total time about five to six years if all goes smoothly

1996 NAC Report (waiting lists, health costs and liquid handcuffs ) 1340 OST patients (1992) 2500 OST patients (1995) $4,400 MMT compared with $50,000+ prison Five models for MMT cost-effectiveness analysis Recommendation Integrated model (80/20) recommended Pharmacological alternatives to methadone

2001 NAC Report (continuing waiting lists) 2500 OST patients (1995) 3800 OST patients (1996) but waiting lists continued to grow Majority of programmes (SI) had a waiting time of at least nine months Recommendation Interim methadone programmes, to reduce waiting time to no more than two weeks

Perhaps the greatest problem facing those working in the field of methadone maintenance treatment (MMT) in New Zealand, is that of waiting lists for treatment. Delay in starting treatment is contrary to the harm reduction principles on which MMT is founded, and exposes clients to ongoing harm Dr Alistair Dunn (2002)

The NZ Experience of IMP 2005 Whangarei Alistair Dunn Wanganui Tracey Fear Palmerston North Martin Schroder Nelson Lee Nixon Christchurch Elle King Dunedin David Mellor

Ministry of Health National Guidelines: Interim methadone prescribing 2007 When there is a longer than two-week waiting list, that patients with established opioid dependence be given the choice of undertaking an interim methadone-prescribing programme, ideally by the patient s own general practitioner, up to a maximum of 60mg.

2008 NAC report (review of MMT in light of P epidemic) Interim prescribing not being widely utilized Majority of programmes with waiting times > two weeks Not ready a new waiting list category in some jurisdictions 3800 OST patients (1996) 4608 OST patients (2008) 25% GP (2008) - MOH goal of 50% - NAC recommendation 80% Barriers identified to accessing OST Buprenorphine recommended

The barriers to accessing OST * OST staff and opioid users agreed: - Having to go on a waiting list - Restricted takeaways - Being tied to staying in one place - Having to go to a chemist every/most days * Almost all services reported significant resource issues and barriers to the transfer of stable patients to primary care

The last four years Interim prescribing not widely utilized Many programmes still have waiting times > two weeks But increase in GP liaison, co-existing disorder competence, national collegiality (NAOTP) 4608 OST patients (2008) 5018 OST patients (2012) 25% GP (2008) up to 29% (2012) Advocating for buprenorphine continued And now, Suboxone appears

With Suboxone A new era in OST is beginning No more opioid deaths No more medication diversion Co-existing disorders including antisocial personality disorder will virtually disappear Stigma will be quickly become a thing of the past and a new opioid addiction units will likely be built adjacent to all regional hospitals in New Zealand The government will soon be announcing a new stream of $500,000,000 funding for opioid service development to compensate for its underfunding of opioid addiction treatment over the past 40 years

With Suboxone A new era in OST is beginning OST for those who can t tolerate methadone Medication alternative will help normalize clinical practice (discussion, choice) Safety profile should facilitate interim prescribing waiting times could easily become the same as for Tb (< two weeks) Greater flexibility possible doubled up doses, more takeaway doses

Suboxone (buprenorphine/naloxone) Registered with Med Safe in 2005 Listed 1 st July 2012 on the Pharmaceutical Schedule Fully funded for detoxification and maintenance treatment in opiate dependent patients

Agonist or Antagonist? Full Agonist - binds to the receptor producing an almost linear increase in physiological effect eg Heroin, Methadone, Morphine Partial Agonist - binds to the receptor but has a ceiling effect on receptor activation eg Buprenorphine Antagonist - binds to the receptor but does not produce a biological response and is able to block agonist effects eg Naltrexone

Suboxone Combination sublingual tablet comprising of buprenorphine and naloxone in a 4:1 ratio Available as 2mg/0.5mg and 8mg/2mg sublingual tablets

Buprenorphine Pharmacology Semi synthetic opioid Agonist (partial) for the mu (μ) opioid receptor and antagonist for the kappa (κ) receptor High affinity for the mu opiate receptor Binds more tightly to the receptor than most other opiate agonists or antagonists Slow association and dissociation rate from the receptor Long duration of action, low physical dependence liability, milder withdrawal Highly lipophilic

Breaths/Minute Score Ceiling Effect Walsh et al (1994) demonstrated that buprenorphine has a ceiling effect for subjective drug liking effects and respiratory depression, consistent with its partial agonist classification Ceiling effect on respiratory depression Subjective effects: plateau 17 16 15 Human respiratory rate 50 40 Drug effect 14 13 12 11 30 20 10 10 0 1 2 4 8 16 32 PL Buprenorphine (mg, sl) 0 P 1 2 4 8 16 32 Buprenorphine dose Adapted from Walsh et al., 1994 Adapted from Walsh et al., 1994

Oxycodone

Kg/million population Per capita oxycodone base supply USA, Canada, Australia (1997-2008) 160 140 120 100 80 60 40 20 0 USA Canada Australia 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 60 kg/million population Source: INCB Tables of Reported Statistics, 2009, US Census Bureau int l database

New Zealand (2006 2009) Number of oxycodone prescriptions in NZ (Pharmaceutical Warehouse data)

Medicines Control Ministry of Health This dramatic increase is difficult to explain on any grounds other than successful marketing by the drug companies. It has no clinical advantage over other agents already available in NZ. Oxycodone should be considered a second line potent analgesic, for use only when morphine is not tolerated. The abuse potential is high: oxycodone is a potent analgesic with high dependence potential and is easily extracted from the longacting formulation for intravenous use. Dr Adrian Gray

M Eslon 160mg $1.49 LA Morphine 160mg $1.57 Oxycontin 80mg $2.49

Opioid addiction treatment Where are we going? 1990s Primary Care (20%) 32x Specialist Care 2x (80%) 2020s (20%) (80%)