buprenorphine induction continued:...

Colorado Opioid Synergy Larimer and Weld

Buprenorphine Induction Continued:

MicrodosingNORTHERN COLORADO MAT LEARNING FORUM

Lesley Brooks, MD

Thursday, April 4, 2019


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.

https://www.btodrems.com/Portal/Content Library/Appropriate Use Checklist.pdf


“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


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.


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


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


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


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


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


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


MicrodosingProtocol Hammig group asked

pharmacy to cut tablets into quarters

Pharmacy board does not allow pharmacists to cut

- Ask for guidance


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


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


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?


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


Thank you!

Who’s got a case?

buprenorphine induction continued:...

Documents