Welcome to today’s Insight APSAD webinar. • Use the chat icon for all questions and comments – select All panelists and attendees. • If you are on a computer and Zoom enters full screen mode – you can press the escape button or visit “View Options” at the top of the screen to change the layout. • If you are experiencing other problems or require further technical assistance call Zoom on 1800 768 027 – the webinar ID is 973-118-396-68. • A pdf version of today’s presentation will be available soon in the chat window. • A recording of this webinar will be available on our YouTube channel in the coming weeks. We’ll be starting a little after 10am (QLD time).
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Welcome to today’s Insight APSAD webinar.
• Use the chat icon for all questions and comments – select All panelists and attendees.
• If you are on a computer and Zoom enters full screen mode – you can press the escape
button or visit “View Options” at the top of the screen to change the layout.
• If you are experiencing other problems or require further technical assistance call Zoom on
1800 768 027 – the webinar ID is 973-118-396-68.• A pdf version of today’s presentation will be available soon in the chat window.
• A recording of this webinar will be available on our YouTube channel in the coming weeks.
Codeine dependence with buprenorphine: A presentation on
two local studiesDr Sarah Reilly with thanks to co-researchers & supervisors:
- Dr Mark Daglish & Dr Jeremy Hayllar
Definitions u ADS: Alcohol and Drug Services (usually refers to public)
u CACC: Combination analgesics containing codeine
u OTP: Opioid treatment program –
u including treatment with buprenorphine and methadone
u MATOD: Medication Assisted Treatment of Opioid Dependence
u OTP + holistic psychosocial support
Talk outline 1. Background on codeine dependence 2. Review outcomes of a retrospective study on treatment of codeine dependence with buprenorphine 3. Discuss second trial, recruitment underway. No results yet!
The opioid crisis: >70 000 deaths in the US last year from overdose (predominantly opioid)
Codeine use in Queensland MATOD clinics
Codeine dependence pre 2018
u Codeine – the ‘weak’, ‘socially acceptable’ opioid
u Limited evidence of analgesic superiority
u In 2016 3.6% of Australians had recently used pharmaceutical analgesics for non medical purposes (1)
u 75% had used CACC (Likely to be >500 000 Australians).
u Morbidity and mortality associated with codeine over-use is significant
u “For every two S8 opioid deaths in 2009, there was one codeine-related death”. 3
u Ibuprofen:
u Renal tubular acidosis
u Hypokalaemia
u GI bleeding: ulcers/perforation/anaemia
u Paracetamol:
u hepatotoxicity 1) National Drug Strategy Household Survey (2016/2019)2) The extent and correlates of community-based pharmaceutical
opioid utilisation in Australia3) Roxburgh et al: Trends and characteristics of accidental and
intentional codeine overdose deaths in Australia. 2015
Codeine… an unpredictable drug
u Morphine is converted to codeine by the P450 2D6 isoenzyme systemu 2D6 efficiency varies leading to
unpredictable morphine levels
u Poor metabolisrs (PM) = no analgesia
u Ultra-rapid (UM) metabolisers produce greater morphine than expected
u Risks include unintentional overdose by respiratory depression – especially in breast-fed babies, children and polysubstance users.
u Insidious tolerance and dependence in ultra-rapid metabolisers.
“Prepare for the Influx”u Between 2007 and 2016, the
number of treatment episodes for codeine dependence rose from 5.9% to 14.1% (1)
u In 2016, 17.1% of people on OTP listed codeine as their primary drug of concern (2)
u ADS prepared for an increase in codeine related presentations post rescheduling
1) Non-Medical use of pharmaceuticals: Trends, harms and treatments (2006-2007 to 2015-2016)
2) NOPSAD – 2019 data
Research Opportunities
u 1. How did presentations change
u 2. Literature review of treatment of codeine dependence
u 3. Retrospective chart review of two metro north ADS
u Patients initiated on OTP for codeine dependence
u What led to their dependence
u How were they treated
u Recently completed for a scholarly project
u 4. Cross sectional genetic study looking at the frequency of ultra-rapid metabolisers in patients on OTP for codeine dependence
u Pharmacogenomics study – ongoing
Changes in type and number of ADS presentations at Biala
2. Literature review: Identifying and managing codeine dependence
Literature review Nielsen (up to 2016) Repeated literature review (2018-2020)
* Nielsen S et al. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database of Systematic Reviews 2016
Describing people with codeine dependence
Compared to illicit substance users: u More women (50/50 v 30/70)
u Higher rates of
u Employment/positive social supports
u Chronic pain
u Psychiatric comorbidity
u Lower rates of
u criminal activity/substance diversion
u Homelessness
u IVDU
Two main reasons for codeine use: u Pain – “legitimate”, “chronic pain issue not an addiction issue”,
u Other – “secret solace”, “mood elevator”, “Social confidence”, “stress relief”, “use associated with shame”,
u Both groups had insidious escalation. Group 1 overlaps with group 2
Most users were hesitant to access ADS treatment. u Most had never sought help due to:
u “Stigma”, “lack of knowledge about pain”, “OTP being restrictive and demeaning”
Applying general guidelines to the codeine using population
u Stepped care approach
u Withdrawal verse maintenance treatment
u Maintenance has better outcomes
u Queensland OTP retention goal of 40% at 12 months
u Maintenance OTP: Bup v Methadone
u Based off patient preference, previous treatment, pattern of opioid use, comorbid conditions and other medications
u Cochrane review on pharmaceutical opioid dependence
u Equal efficacy, buprenorphine slightly better tolerated (small number of studies).
u Buprenorphine Dose range of 12-24mg
u Receptors saturated at 16mg
u Methadone: >60mg
Treatment of codeine dependence at two Metro North ADS (study 1)Retrospective chart review• Convenience sample of patients initiated on OTP for codeine dependence
• Jan 2016 and July 2018• Codeine must have been the PRIMARY drug of concern• OTP dose must have been available• Must have been initiated on buprenorphine
Aims: 1. Describe demographics and comorbid conditions of codeine dependent patients2. Describe buprenorphine prescribing patterns 3. Assess the association between codeine and buprenorphine doses
Flow of included patients
u 112 OTP episodes for codeine codeinedependence (11% of OTP registrations. Higher numbers at melaleuca)
Association between codeine and buprenorphine doses
Limitations
u Accuracy of data
u Recall bias
u Researcher’s were not blind
u Comorbid diagnosis was based off self disclosure rather than formal assessment
u Likely to under-report personality disorder and trauma history
u Potentially will under-report other substance use due to fear of stigma
u Limited to treatment of severe codeine dependence
u Ideally results would be replicated in a larger, prospective study
Conclusions of study 1
u Small statistically significant association between maximum codeine and buprenorphine dose – PROBABLY not clinically significant
u Codeine using patients required a median buprenorphine dose of 18mg
u Within the 12-24mg recommended in OTP guidelines
u Buprenorphine favoured over methadone ++
u The service achieved 40% retention in this group!
2nd study : Phrmacogenomics: Are UM at greater risk of opioid use disorder?
u Currently underway across our two clinics - 43 patients recruited at present – hoping to at least double that
u Aim: determine whether patients who are codeine “normal” metabolisers (NM) and “ultra-rapid” metabolsiers (UM) are overrepresented among those who have commenced opioid treatment for a codeine use disorder.
Hypothesis
u 1. Higher prevalence of efficient metabolisers in patients with codeine use disorder, compared to the general population
u 2. UM will require higher doses of buprenorphine proportionate to their stated codeine intake
Methods
u A specific CYP2D6 assay previously validated in an Australian population (Moustafa et al) is being used – samples sent to Melbourne
u Clinicians are encouraged to continue to recruit patients who are receiving OTP. Simple buccal swab. Patients are able to find out their results
u $30 coles voucher available
Thoughts for the future
u Possibly CYP2D6 genotyping prior to prescription of codeine (and maybe anti-depressants)
u Need to be aware of the overdose risk associated with Codeine
u Consider Naloxone scripts
u Focus on multi-disciplinary, non pharmacological measures for chronic pain:
u Chronic disease model approach
u Allied health: Physio, psychology and OT
u Psychiatrist and or addiction specialist
u Pain specialist
u General practitioner
Thanks for joining us today!
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