Colorado Opioid Synergy Larimer and Weld
Buprenorphine Induction Continued:
MicrodosingNORTHERN COLORADO MAT LEARNING FORUM
Lesley Brooks, MD
Thursday, April 4, 2019
Colorado Opioid Synergy Larimer and Weld
To Review… Bupe induction and
maintenance checklist
Need for withdrawal prior to induction
Home vs Office Induction
Microdosing
Ref: https://www.btodrems.com/Portal/Content%20Library/Appropriate%20Use%20Checklist.pdf
Short acting opioids• Most patients dependent on short-acting opioids.
Heroin and many Rx narcotics = short acting.• Abstinence timing for short-acting is 12-16 hours;
for intermediate-acting is 17-24 hours
Long acting opioids • Due to longer action, patients must abstain longer
before induction.• May need "comfort" medicine (e.g., non-opioid
analgesics, non-benzo anxiolytic, antidiarrheal agents, antiemetics, antispasmodics) for withdrawal after the first day until a stable dose
• Treat induction for long-acting opioids with care, as precipitated withdrawal more likely.
• Methadone (MTD) = long-acting. Transferring from MTD requires additional steps: taper to 30-40mg daily, then abstain for 36hrs after last dose.
Colorado Opioid Synergy Larimer and Weld
“In-House” / Office Induction – J. Dubin
COWS score 12-15 1st dose 2-4 mg under observation in office or inpatient setting. Observe in office for at least 1 hr, document effect. Repeat dose to
comfort. 1st day’s dose may range from 2-16 mg. Lower doses required in those with
lower level of physical dependence. If withdrawal occurs after patient leaves the office, request patient return
to clinic. Avoid this complication by taking the time to assure moderate withdrawal discomfort prior to the first dose. Remain in contact with patient by phone during 1st 1-2 days; adjust dose as
needed over next 5-7d Give sufficient medication only until the next visit, within 3-7 days
Colorado Opioid Synergy Larimer and Weld
Home Inductions – J. Dubin
Good candidate:– Pt who has had patient education– Previously treated patients known to be reliable– patients who demonstrate knowledge of the risks of unobserved induction, willing to
come to the office in the event of problems.
Suboptimal candidate:– patient has expressed significant fear of withdrawal– May starting buprenorphine too early and causing a precipitated withdrawal.
Provide explicit written instructions and SOWS/COWSMaintain close telephone/office contact with patient during course of
induction Have patient return within 2-7 days of starting buprenorphine.
Colorado Opioid Synergy Larimer and Weld
Home Induction: Education Handout Example Educate pt on when to start bupe
(in AM)- # hrs since last dose, - sx they should have prior to
starting
Describe what dose to take, how to take it
- 4-8 mg under tongue
Explain- when they will feel better- what to do if they don’t (another
dose in 1-3 hrs)- Max dose on 1st day- when to call the clinic- when to return for follow up
Colorado Opioid Synergy Larimer and Weld
Microdosing
Methadone (MTD)– Works well for many, improved retention in treatment over bupe
– requires no abstinence period
– Limitations include daily dosing, geographic location, drug-drug interactions, careful titration to avoid side effects
Buprenorphine (bupe)– Also works well for many; slightly less effective at retention in
treatment vs MTD
– Improved side effect profile, few drug-drug interactions
– requires presence of withdrawal; can itself precipitate w/d if abstinence timing insufficient
Colorado Opioid Synergy Larimer and Weld
Induction Challenges
Conventional Bupe Induction– Despite precautions, can lead to precipitated w/d
– Can be a difficult experience for the person with OUD
– Can lead to risk of relapse to illicit opioid use
Hammig et al (University of Basel Psychiatric Hospital, Switzerland)– Published “Use of microdoses for induction of buprenorphine treatment with
overlapping full opioid agonist use: the Bernese method”, Substance Use and Rehabilitation, 2016
– Will review this method today
Colorado Opioid Synergy Larimer and Weld
Hammig et al: Microdosing Hypotheses
Based on slow bupe kinetics, observation that small doses of IV bupe did not produce w/d in MTD patients…
– Repetitive admin of small bupe doses w/ short (12hr) intervals should not w/d
– Bupe will accumulate at the receptor– Over time, increasing amounts of full agonist will be replaced by
bupe at receptor
Proposed: overlapping induction of bupe in persons with ongoing use of street heroin or high-dose full agonist (MTD) w/o severe w/d sx
Colorado Opioid Synergy Larimer and Weld
Hammig: Case 1
F, middle-class, Swiss family– Hx of…sexual abuse, PTSD, poly-SUD (cocaine, psilocybin, MDMA, cannabis,
heroin), MDD w/ suicide attempt, bulimia…all b/w 12-18yrs– Mult attempts at bupe maintenance; bupe mono as bup/ntx not avail in SZ– 30yrs of age at time of presentation to Univ Basel, 3g/day street heroin
Conventional induction severe w/d, trauma-related flashbacks, anxiety
– Returned to heroin use after 2 weeks– Again returned to program for re-induction but nervous about tolerability of
process
Colorado Opioid Synergy Larimer and Weld
Hammig: Case 1
Implemented Bernese Method/Microdose Induction– Started with low dose bupe – 0.2mg
– overlapping with heroin use
– small daily dose increases
– abrupt cessation of heroin/full agonist when target dose reached
Case 1 stabilized at 12mg/d bupe– Has relapsed several times w/ heroin, re-initiated bupe with Bernese method
– Experienced another episode of MDD, tx’d with escitalopram & therapy
– Stable off heroin x 2.5yrs
Colorado Opioid Synergy Larimer and Weld
MicrodosingProtocol Hammig group asked
pharmacy to cut tablets into quarters
Pharmacy board does not allow pharmacists to cut
- Ask for guidance
Colorado Opioid Synergy Larimer and Weld
Hammig: Naltrexone Microdosing Protocol
Case 1 desired complete abstinence; wanted to initiate NTX for craving
– Hammig et al. assumed NTX could be started similar to overlapping bupeinduction
Case 1 tapered off bupe to 2mg/d then– Used small amounts of NTX (“scratched off from 50mg tablet”) with daily
increases– Did not develop w/d sx or cravings– Stopped bupe, increased NTX to 25mg/d– After several months, stopped NTX 3yrs 3mos abstinent at publication
Colorado Opioid Synergy Larimer and Weld
Naltrexone Microdosing
Here is another microdosingexample that might be slightly easier to reproduce
Oral naltrexone comes in 50mg tablets
Microdosing of 0.125, 0.250, 1mg, etc requires compounding pharmacy
Local solution for microdosing…??
Day # NTX Dose Methadone Dose
1 0.125/0.250mg 30mg
2 0.125/0.250mg 25mg
3 0.125/0.250mg 20mg
4 0.125/0.250mg 15mg
5 0.125/0.250mg 10mg
6 0.125/0.250mg 5mg (last day)
2008, Mannelli et al
Colorado Opioid Synergy Larimer and Weld
No clearly established criteria. Venue as important as Rx.
Some things to consider…
- What is your patient’s preference?
- How stable is your patient?
- Is the person pregnant?
- What is their treatment history?
- How severe is their use disorder?
- Are there co-occurring disorders?
- How strong is their support system?
- What kind of and how much structure do they need?
- Can the person stop using long enough for induction?
MAT – Which MAT is best for my patient?
Colorado Opioid Synergy Larimer and Weld
References
1. Hämmig, Robert et al. “Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method.” Substance abuse and rehabilitation vol. 7 99-105. 20 Jul. 2016, doi:10.2147/SAR.S109919
2. Mannelli, Paolo et al. “Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial.” Addiction biology vol. 14,2 (2008): 204-13. doi:10.1111/j.1369-1600.2008.00119.x
Colorado Opioid Synergy Larimer and Weld
Thank you!
Who’s got a case?
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