Opioid And Benzodiazepine Reduction Strategies
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Transcript Opioid And Benzodiazepine Reduction Strategies
Opioid and
Benzodiazepine
Reduction
Strategies
Launette Rieb
MD, MSc, CCFP, FCFP, dip. ABAM
Clinical Associate Professor,, Department of
Family Practice, University of British Columbia
Disclosures
No
commercial interests
Objectives
Clarify
the pharmacology of opioid and
benzodiazepine use and withdrawal
Increase skill at detoxifying patients from
opioids and benzodiazepines using the
following techniques:
Opioid withdrawal symptom management
Opioid tapering
Opioid substitution
Papaver Somniferum
Opioids
Bind to opioid receptors
Relieving pain (psychological and physical)
dopamine (DA) in pleasure centres (ventral
tegmental area nucleus accumbens)
noradrenalin (NOR) in the fight or flight centres
(locus coeruleus and amygdala), calming
Affects brainstem (OD from respiratory depr.)
Can produce dysphoria, sedation, impaired
judgment, constipation, weight gain, erectile
dysfunction (from decreased testosterone)
Opioids – Higher Doses
Can increase the risk of…
Unintentional
OD
Substance misuse and addiction
Tolerance
Via NMDA pathway activation
Opioid receptor desensitization, internalization
Opioid Induced Hyperalgesia
Via NMDA pathway activation
Suppression or even cell death among
descending pain control neurons
Dose-related risk of opioid
overdose Risk of adverse event
10
9
8
7
6
Dunn 2010
Risk Ratio 5
Bohnert 2011
Gomes 2011
4
Zedler 2014
3
2
1
0
<20 mg/day
20-49 mg/day
50-99 mg/day
Dose in mg MED
>=100 mg/day
Courtesy
Gary Franklin
Prescription Opioids
“Watchful
Dose”
in
morphine equivalent daily dose (MEDD)
120 mg Washington
120 mg Worksafe BC
200 mg Canadian Opioid Use Guidelines
only 20-30% with LOT –Yet we chase
the fantasy of perfect analgesic control
Analgesia
Withdrawal
can be very painful (especially at
sites of old injury) drive further use
Opioid Withdrawal
Withdrawal is not life threatening
Unless
patient has a history of seizures, is
dehydrated, suicidal or pregnant
Warn patients of OD risk post detox
Opioid Withdrawal
DSM-5…3+
within minutes to days of stopping:
Dysphoria
N or V
muscle aches
lacrimation or rhinorrhea
diarrhea
yawning
fever
insomnia
Pupillary dilitation, piloerection or sweating
When to Suggest Opioid Taper?
Patient on opioids without significant
improvement in pain and function
Safety sensitive position
Spread of pain in the absence of disease
progression
allodynia and hyperalgesia
Active substance abuse/dependence where
harm reduction not viable
Patient requests to come off
Where to start?
First
make a diagnosis
Use? Substance Use Disorder? Pseudoaddiction?
Is
there physiologic dependence?
Is a withdrawal syndrome present?
How severe? Life threatening?
What
is the patient’s circumstance?
Support setting? Mental and physical
health?
Opioid w/d Management
Protocol
for short acting opioids like morphine,
oxycodone or heroin
For use when you cannot or will not prescribe
opioids, eg street opioid use
A
caregiver should accompany patient to
appointments, agree to attend & dispense then you can give 1 week’s worth of meds
Daily dispensed from the pharmacy if reliability
of the caregiver an issue
Opioid w/d Management
Environment:
Reliable support person, safe, no
caffeine, mild food, min exercise, avoid hot
bath/shower/sauna
Clonidine
0.1mg qid x4d, tid x1d, bid x1d, hs x1d
all prn
Test dose 0.1mg, BP pre & 1-4h post in the
office can be done (eg. For young women)
BP >90/60, if lower - give clonidine 0.05 mg
tabs
Decreases temperature dys-regulation
(hot/cold flashes) and NOR (insomnia &
anxiety)
Warn pts of postural hypotension
Opioid w/d Management,
Diazepam*
5 mg qidx4d, tidx1d, bidx1d
Decreases anxiety, insomnia
If benzo tolerant: 10mg dosing – close f/u
Trazodone*
50 mg 1-2 tabs hs for insomnia
Loperamide 2 mg after loose stool, 8/d max
Dimenhydrinate 25mg 1-2 tid N+V
Ibuprofen 400 mg q 6-8h for pain
Acetaminophen 500mg q6h for pain
* Nb quetiapine 25 mg tid and 100 hs can be
used instead of diazapam and trazadone
Opioid w/d Management,
Try
to start on a Monday (not Friday)
Try to start medicines after 1d off heroin/morph
Try to see or call in frequently
Adjust medications according to symptoms
If patient relapses, review symptoms (ask what
was the worst part of the w/d) and try again –
adjusting meds.
Make a backup plan in the beginning – eg. if
home detox fails x2 then residential detox or
methadone (often more effective than detox)
Opioid Tapering Options
Options to withdrawal from legally obtained
Rx opiates for pain (not addiction):
1.
2.
3.
Taper with current short acting
medication formulation
Convert short acting into long acting of
the same opioid, then taper
Substitute another type of opioid then
taper. AKA opioid rotation.
Opioid Tapering – Short
Acting
Sometimes
easiest to simply taper what
the patient is currently using – even if short
acting
E.g. Oxycodone/APAP 16-20/d, taken 6 tid
+/- 2/d
If
it is a dual agent first switch to eliminate
the ASA or acetaminophen (bloodwork?)
E.g. Oxycodone 5 mg 18/d
Next
spread out the daily dose evenly
based on the ½ life of the medication
E.g. Oxycodone 5 mg 5/4/4/5 spread q6h
Opioid Tapering – short
Next
taper the medication – depending on the
patient’s symptoms the drop can be ever 4 -14
days, always dropping nighttime dose last
Oxycodone 5 mg 4/4/4/5 spread q6h
Oxycodone 5 mg 4/4/4/4 spread q6h
Oxycodone 5 mg 4/3/4/4 spread q6h
Oxycodone 5 mg 4/3/3/4 spread q6h
Oxycodone 5 mg 3/3/3/4 spread q6h
Oxycodone 5 mg 3/3/3/3 spread q6h
Continue this pattern until 0/0/0/1, then off
Opioid Tapering – short
If
patient using a combination of short and long
acting – conventional wisdom is to taper short
first, but since often this is what patients “feel”
and are attached to you can taper it last
Oxycodone ER 80 mg q12 h plus oxycodone
10mg 1-2 prn 4/d max
Taper Oxycodone ER first by 10 mg every 4-14
days dropping morning dose, then evening dose
Hold the oxycodone short 10 mg at q6h until off
the Oxycodone ER then taper by 5 mg as per
previous schedule leaving the hs to be last off
Opioid Tapering - convert
Conventional
wisdom is to convert short acting
opioids to long acting then taper Sometimes
short is needed to add back in at the end due to
dose strength
Convert to long acting (same drug less 25% - 50%,
rest is given as short acting PRN at 1st)
If
changing opiates beware of conversion
Lack of cross tolerance with some opiates
Once on just long acting: Taper ~5-10% per wk
If the patient has lots of social support can try
tapering 10% q 4d
Opioid Tapering – Convert
Pt
taking hydromorphone (short) 200 mg/d
1st conversion: Hydromorphone (long) 75 mg q12
h plus hydromorphone (short) 4mg 1q4h prn –
warn about driving, sedation
2nd week: see if prn doses needed – if so add in as
long acting, e.g. 100 mg q12h
3rd week on…taper 5-10%, typically faster at first
and slower at the end of the taper
Taper until on lowest dose strength long 3q12h
Then re-introduce short to complete weekly
taper, e.g. hydromorphone (short) 2mg q8h; 1mg
q6h; 1mg q8h; 1mg am and hs;1mg hs;off
Risk of Addiction (or Relapse)
Those at highest risk:
Active SUD
Past Hx of SUD
Family Hx of SUD
Active psychiatric illness
Past Hx of chronic pains requiring opioids++
Tight contracts, follow-up, and collateral
In Patients at High Risk for SUD
Prescribe
only for well-defined somatic or
neuropathic pain conditions
Start with lower doses and titrate in small dose
increments
Monitor closely for signs of aberrant drug
related behaviors – send for assessment and
treatment if needed
Alcohol and benzodiazepine use is
incompatible with opioid prescribing
Opiate
Addiction
Abstinence
Counseling
Medications
Agonist
Peer Support
Methadone
Residential
Treatment
Buprenorphine
Antagonist
Naltrexone
Opioid Substitution Therapy
Methadone and buprenorphine/naloxone
(bup/nx) can be used for pts with an opioid use
disorders and pain
Dose
once daily to eliminate withdrawal and
block other opioids – may be sufficient
Methadone or bup/nx used for pain +/- SUD
can be dosed q6-8h
Bup/nx currently off label for pain alone though
can argue physiologic dependence, tolerance
Methadone and bup/nx are used for detox
METHADONE
Morphine to Methadone
Oral morphine to methadone
24 hour total oral morphine
conversion ratio
<30 mg
2:1
31-99 mg
4:1
100-299 mg
8:1
300-499 mg
12:1
500-999 mg
15:1
>1000 mg
20:1
Managing Cancer Pain in Skeel ed. Handbook of Cancer
Chemotherapy. 6th ed., Phil, Lippincott, 2003, p 663
Results
646/4183
sustained successful tapers = 13%
Younger, males, better tx adherence, lower
mean max weekly doses
Longer tapers better
12-52
weeks vs <12 weeks OR 3.58
>52 weeks vs <12 weeks OR 6.68
More
gradual, stepped tapering schedule
25-50%
vs <25% of taper weeks OR 1.61
Patterns of Methadone Dose Tapering
(Most successful checked)
Modified from Nosyk et al, Addiction 2012; 107(9):1621-9.
Precipitated Withdrawal
Buprenorphine/naloxone – bup/nx –
only a “partial agonist” in vitro, but is
really a full agonist at the mu opioid
receptor in vivo
slightly better than morphine for receptor
saturation and pain relief
Has higher AFFINITY for the mu opioid receptor
than anything but fentanyl thus will kick off
other opioids and put the person into
withdrawal until the buprenorphine is high
enough to relieve withdrawal
kappa receptor antagonist, may help mood
Bup/nx and Pain
Daitch D et al. Pain Medicine. 2014
Retrospective chart review of patients on over 200 MEDD converted to Suboxone
- pain scores dropped 51% on average, 8/10 to 4/10
Average 4 point drop!
Daitch D et al. Pain Medicine. 2014
Naltrexone – opioid antagonist
Post
detox use naltrexone 50mg/d po
for those with OUD
can block 0.5+ gm of heroin IV or equivalent
Start
1-2 wks after last short acting
opioid (3-4 wks post methadone)
¼ pill day 1; ½ pill day 2; 1 pill day 3 onwards
Witnessed ingestion is best
Contraindicated
cirrhosis, OD risk high once d/c
Use for first 6-12 months of sobriety from OUD
Analgesia with non-opioids or get consult
Naloxone Take Home Kits
Nasal
or injectable naloxone kits given to
people prescribed opioids for pain or
addiction
Train Pt and others living with them
Can save lives in OD situations
Sometimes Pt uses it on a friend
Find out what is available/allowable in
your area
Evidence for Use
Only real indication is for alcohol withdrawal
Poor evidence for Generalized Anxiety Disorder,
Obsessive Compulsive Disorder, Post Traumatic
Stress Disorder, Major Depressive Disorder
(including augmentation), or schizophrenia
May be indicated for short term therapy in
insomnia or acute anxiety short term (i.e. panic
disorder) but note that needs CBT alongside
and can create refractory anxiety – not a
monotherapy indication
Benzo - Adverse
Cognitive
Effects
Acute (sedation, impairment of learning, slowing,
anterograde amnesia)
Chronic (visuospatial impairment, reduced cognitive
functioning)
Increased Alzheimer’s OR 1.4 (Billioti BMJ Aug 2014)
Psychomotor
Effects
Driving ability
Falls, accidents and injuries
Mortality
– HR 3.6 – 5.3 (Kripke BMJ 2012)
Contraindicated with other sedatives e.g. ORT like
methadone, bup/nx, alcohol, muscle relaxations –
studies show increased mortality
Benzodiazepines
Binds
to GABA-BNZ receptors and allow chloride to enter
cell thus hyperpolarizing it
Withdrawal criteria same as for alcohol
Both use and w/d can be life threatening
Residential detox if both ETOH & benzo (polypharmacy)
W/d may last weeks, occasionally months
High dose, long duration, short acting benzos all risks for
difficult or prolonged w/d
Meta-analysis on tapering protocols inconclusive of the best
rate – best to engage patients, some promise with substitute
therapies
Benzodiazepine – withdrawal
Discuss
Anxiety symptoms – irritability, insomnia, panic
attacks, poor concentration
Neurological symptoms – ringing in the ears, blurred
vision, distorted perception, depersonalization
Let
with patients what to expect:
them know if they get shaky to stop taper
Tremor is clearest sign pre-seizure
Need to reassess, perhaps take extra dose
Benzodiazepines – w/d
Abrupt
Risk seizure, psychosis or delirium
Consider residential tx if abrupt cessation >80mg
Office
cessation of > = diazepam 50 mg/d
mngt: Convert to long acting benzo
Smooth blood level decreases symptoms
Diazepam can be used if young and healthy
Clonazepam good alternative for w/d from
alprazolam or triazolam
Lorazepam if cirrhosis or elderly
Benzodiazepines - Tapering
Give
75% diazepam equiv. - divided q8h
Plus breakthrough prn doses of the rest
Reassess
in 1 week or less, establish dose
Taper diazepam by 2–5 mg q1-2 wks (5%)
No regular breakthroughs
If short term use – faster, if long term – slower
Can initially drop faster if dose over 50 mg/d
Trazodone 50 hs or propranolol 10-20 tid may help decrease
prolonged w/d symptoms
Benzo tapering – another
approach
Alternatively
you can substitute in the diazepam
slowly while decreasing the other benzodiazepine
Since there may not be perfect cross tolerance
some find this more comfortable
Some find lorazepam more anxiolytic and
diazepam more sedating
Diazepam allows the dose to go lower before
discontinuing.
Benzodiazepine equivalences
Adapted from The Ashton Manual and The Clinical Handbook of
Psychotropic Drugs (19th Ed.)
Benzodiazepine
Comparative Dose (mg)
Alprazolam
0.25-0.5
Clonazepam
0.25
Lorazepam
0.5-1
Diazepam
5
Oxazepam
10-15
Temazepam
10
Ashton Protocol
Dr.
Heather Ashton from the UK
Protocol for very slow benzo conversion
and taper of diazepam (can apply the
same principle to opioid tapering if
needed)
Use for highly sensitive patients
Those on for many years
Elderly
Failed conventional tapering
Withdrawal from lorazepam1mg TID
Adapted with permission from slides of R. Chadha
Stage
Morning
Afternoon
Evening
Stage 1
(1/52)
Loraz. 1 mg
Loraz. 1 mg
Loraz. 0.5 mg 30 mg
Diaz. 5 mg
Stage 2
(1/52)
Loraz. 0.5 mg Loraz. 1 mg
Diaz. 5 mg
Loraz. 0.5 mg 30 mg
Diaz. 5 mg
Stage 3
(1/52)
Loraz. 0.5 mg Loraz. 0.5 mg Loraz. 0.5 mg 30 mg
Diaz. 5 mg
Diaz. 5 mg
Diaz. 5 mg
Stage 4
(1/52)
Loraz. 0.5 mg Loraz. 0.5 mg (Stop Loraz.)
Diaz. 5 mg
Diaz. 5 mg
Diaz. 10 mg
30 mg
Stage 5
(1/52)
(Stop Loraz.)
Diaz. 10 mg
30 mg
Loraz. 0.5 mg Diaz. 10 mg
Diaz. 5 mg
Diaz. Equiv.
Withdrawal from lorazepam
Stage
Morning
Afternoon
Evening
Diaz. Equiv.
Stage 6
(1/52)
Diaz. 10 mg Stop loraz.
Diaz. 10mg
Diaz. 10 mg
Stage 7
(1-2/52)
Diaz. 10 mg Diaz. 7 mg
Diaz. 10 mg 27 mg
Stage 8
(1-2/52)
Diaz. 7 mg
Diaz. 7 mg
Diaz. 10mg
Stage 9
(1-2/52)
Diaz. 7 mg
Diaz. 4 mg
Diaz. 10 mg 21 mg
Stage 10
(1-2/52)
Diaz. 5 mg
Diaz. 4mg
Diaz. 10 mg 19 mg
Stage 11
(1-2/52)
Diaz. 5 mg
Diaz. 2 mg
Diaz. 10mg
30 mg
24 mg
17 mg
Withdrawal from lorazepam
Stage
Morning
Afternoon
Evening
Stage 12
(1-2/52)
Diaz. 3 mg
Diaz. 2 mg
Diaz. 10 mg 15 mg
Stage 13
(1-2/52)
Diaz. 3 mg
(Stop Diaz.)
Diaz. 10mg
Stage 14
(1-2/52)
Diaz. 2 mg
----------------- Diaz. 10 mg 12 mg
Stage 15
(1-2/52)
(Stop Diaz.)
----------------- Diaz. 10 mg 10 mg
Stage 16----------------- ----------------- Reduce by
Completion
1 mg every
2/52
Diaz. Equiv.
13 mg
9 mg – 0
mg
Benzo withdrawal management
Some
other medications have been tried in
withdrawal for symptomatic therapy:
SSRI for depressive symptoms
TCAs, melatonin, trazodone for insomnia
Propranolol for severe palpitations, gastric upset
?Muscle relaxants
No
real good evidence for this but is clinically
relevant in engaging patients in withdrawal
Novel
studies being done with pregabalin,
gabapentin, and other anti-epileptics
Pharmacological assisted
benzodiazepine discontinuation
1st
line: Phenobarbital
Acts as a weak agonist at GABA receptor
Long t1/2, minimal withdrawal, generally
well-tolerated and effective
Dosing: 30 – 60 mg bid – qid
2nd
line:
Gabapentin 100 – 300 mg tid
Pregabalin
50 – 75 mg qhs – tid
(Dr Mark Weiner, Ann Arbor, Mich., Pain
Recovery Solutions)
Effects of pregabalin on subjective
sleep disturbance during withdrawal
from long term benzodiazepine use
N = 282
Pregabalin dose 315 mg/day (mean)
Decrease in insomnia scores (week 12)
Pregabalin 55.8 +/- 18.9
Placebo
25.1 +/- 18.0
Improvements in anxiety symptoms
(Rubio G et al, Eur Addict, Jun 2011)
Residential Detox
When to consider residential detox?
If
unsuccessful with out-patient detox
If out of control with meds
If other SUDs suspected
Patient requests to get w/d over with
faster
Significant psychiatric or physical
symptoms symptoms emerge
Mr. D.
47
year old married at home father, degree is psychology, no
family history of SUD
Age 19: L4-5 discectomy for prolapse
Post-op give Tylenol #3
He mixed these with ETOH to get high
years later – recurrent disc – surgery
Initially successful then increasing low back pain over the
next year
10
Mr. D, con’t
GP managed
Tried different medications, low dose at 1st
Hydromorphone short acting up to 80 mg/d
Would
run out early, would crush and smoke
Fluoxetine 60 mg/d
Lorazepam 4 mg/d
Pain still unmanageable on above regime
Referred on
Mr. D., con’t
Multidisciplinary hospital based pain clinic
Medications altered, various medications combined
Opioids were increased over time to the level below:
Fentanyl Patch 150 mcg/h q2 d (prescribed q3d)
+/- fentanyl solution 100 mcg/2ml vile 3-5/d
Fentanyl film 600 mcg bid = 1200 mcg/d
Tramadol (24h) 50 mg ii bid = 6 tabs/d = 300 mg/d
Methadone tablets 60 mg bid = 120 mg/d
Hydromorphone - short acting 80 mg/d (snorting)
Morphine equivalent dose = 1,830+ mg/d
Mr. D., con’t
Other
medications
Fluoxetine 80 mg/d (adverse rxn - duloxetine)
Diazepam 2.5 mg bid (+still using lorazepam)
Decongestant with pseudoefedrine 2 tabs/d
Caffeine pills and energy drinks
He
still felt pain, otherwise felt “Great!”
Function: ran triathlons, others see sedation
Total cost to wife’s insurance = $3,000/wk
Mr. D., con’t
Voluntary admission to a medically supervised
residential treatment facility: education, 12 step,
group, 1:1, CBT, etc.
Methadone and fluoxetine same dose at 1st
Stopped tramadol on admission
Stopped all fentanyl after 2 d taper
Added quetiapine 25 mg q6h
No withdrawal seen
Mr. D., con’t
Tapered
the methadone over 3 weeks to 5 mg tid
Dose held until in withdrawal
Switched to buprenorphine patch 10 mcg initially
– not quite enough
Then over to sublingual bup/nx titrated to 6 mg/d
where he has been maintained successfully
Mr. D., followup
Follow-up 12 months post admission to recovery
Meds
Bup/nx 6 mg/d
Fluoxetine 60 mg/d and tapering
Quetiapine 125 mg/d and tapering
Has
attended 12 step daily, has a sponsor
No relapses or slips, despite divorcing
No more pain issues
GAF 95/100
Mr. D., Reflections
Primary
pain disorder or substance use
disorder?
Opioid induced hyperalgesia?
How can the opioids besides methadone be
stopped abruptly without withdrawal?
How can bup/nx and 12 step combined
control both the pain and addiction issues?
Opioids - Highlights
Patients
with physiologic dependence
on opioids and/or benzodiazepines who
need to come down or off can be
assisted by a variety of approaches:
Symptom
management
Replacement and tapering
Agonist therapy
Antagonist therapy (naltrexone)
Education and non-pharmacologic options
Key References
Chou, R. et al. The Effectiveness and Risks of Long-Term
Opioid Therapy for Chronic Pain: A Systematic Review
for a National Institutes of Health Pathways to
Prevention Workshop. Ann Intern Med. 2015;162(4):276286. doi:10.7326/M14-2559
Fishman, S. Responsible opioid prescribing, 2nd edition.
2014. Waterford Life Sciences, Washington, DC
Furlan A. et al. Opioids for chronic non-cancer pain: A
new Canadian guideline. www.cmaj.ca and
http://nationalpaincentre.mcmaster.ca/opioid/
Ashton H. The Ashton Manual.Information for Physicians,
Patients, Taper schedules. Website: benzo.org.uk
Kahan M., Wilson L. Managing Alcohol, tobacco and other
drug problems: A pocket guide for physicians and nurses.
CAMH Centre for Addiction and Mental Health, 2002
Thank you!