Module 2: Treatment options

Question 1

Why should medically supervised withdrawal (detox) alone be avoided when trying to achieve opioid abstinence?

Answer 1

• Alone, it rarely leads to abstinence (CRISM, 2018; CAMH, 2021).
• Individuals face higher risk of opioid poisoning due to tolerance reduction.

Question 2

When to consider abstinence-based treatment?

Answer 2

• client prefers it
• younger
• brief history of OUD
• good social supports
• no major psychiatric co-morbidity
• not dependent on other substances
• good past response to abstinence-based treatment (i.e. ++months abstinent after first try)

Question 3

What is the rate of relapse to opioid use following withdrawal management (detox)?

Answer 3

90% by six months (Tuten et al., 2012)

Question 4

Define harm reduction

Answer 4

Approaches that reduce the risk of a behaviour without the expectation the behaviour will stop.

e.g. seat belts and helmets

Question 5

What are some harms that substance use harm reduction focuses on?

Answer 5

• infectious diseases (HIV, Hep B/C)
• opioid poisoning
• injury from IV drug use
• death

Question 6

Naltrexone mechanism of action

Answer 6

opioid receptor antagonist

Question 7

Naltrexone forms

Answer 7

Oral (+ IM in the US only)

Question 8

Patient factors suggesting trial of naltrexone for OUD

Answer 8

• have completed detox/withdrawal
• high motivation
• physically healthy
• better when combined with psychosocial therapy

Question 9

Patient factors that are barrier to naltrexone use

Answer 9

• poor medication adherence history

(see https://www.porticonetwork.ca/web/opioid-toolkit/treatment/naltrexone)

Question 10

1st-4th line treatments for OUD

Answer 10

1. buprenorphine/naltrexone
2. methadone
3. SROM (off-label)
4. iOAT (Injectable opioid agonist therapy) (diacetylmorphine or hydromorphone)

Question 11

What are pros of bup/nlx for OUD?

Answer 11

• superior safety profile
• more flexible take-home dosing

Question 12

OAT pros

Answer 12

bup/nlx and methadone:

• significant reduction all-case and opioid-related mortality
• improves social functioning and QOL
• reduction in use of other opioids
• reduction in high risk behaviour
• reduction in crime
• reduction in opioid poisoning

Question 13

buprenorphine mechanism of action

Answer 13

• partial opioid receptor agonist (mu) + antagonist (kappa)
• attentuates withdrawal
• reduces cravings
• blocks other opioids (b/c high affinity)

Question 14

bup/nlx pros over methadone

Answer 14

• safety: ceiling effect (b/c partial agonist) -> less likely to cause respiratory depression
• convenience: easier to allow take-home doses
• rapid: takes only days/weeks to titrate up to effective dose vs weeks/months for methadone
• less QTc prolonging
• lower risk with diversion
• easier to taper d/t long-half life and partial agonist

Question 15

buprenorphine pharmacodynamics

receptor activity and the effects on the person

Answer 15

• mu partial agonist (high affinity)
• kappa antagonist
• mu agonism = analgesia, resp/LOC depression, pupillary constriction, decreased bowel motility
• kappa antagonism = anti-analgesia and anti-dysphoria

Question 16

buprenorphine - why is activity at kappa receptor important?

Answer 16

anti-analgesia -> less opioid hyperalgesia
anti-dysphoria -> less dysphoria

Question 17

Common Adverse effects of bup/nlx

differentiate persistent vs subside with time

Answer 17

persistent:
constipation
sweating
decreased libido
insomnia
subside with time:
reduced appetite
weight gain
nausea
drowsiness
nervousness

(shared with methadone)

Question 18

Less common adverse effects of bup/nlx

Answer 18

flushing
vomiting
dizziness
dry mouth
swelling of ankles
heaviness in arms and legs
abdominal cramps

Question 19

Mehanism of inducing withdrawal when using bup/nlx

Answer 19

1. bup high affinity for mu -> displacing any full agonist
2. since bup is only partial agonist, activity at receptors drop from high to lower activity -> withdrawal

Even at max dosing, bup/nlx may cause withdrawal for some individuals

Question 20

Indications for methadone

(in general)

Answer 20

OUD and chronic pain

Question 21

pharmacodynamics of methadone

Answer 21

mu full agonist

Question 22

methadone benefits

Answer 22

supress withdrawal
reduces cravings
reduces euphoric effect of other opioids
long acting (vs say heroin)
tolerance develops slowly (years)

Question 23

methadone – common adverse effects

persistent vs temporary

Answer 23

common/persistent:
sweating,
conspitation,
decreased libido,
insomnia

temporary
abdominal cramps
nausea
reduced appetite
drowsiness
nervousness

Question 24

methadone – serious side effects

Answer 24

QTc prolongation
sedation / cognitive dulling
resp. depression

(dose-dependent, therefore suggest dose is too high)

Question 25

Indications for SROM (slow-release oral morphine)

Answer 25

contraindications, intolerable side-effects, or inadequate reponse to bup/nlx or methadone

Question 26

What must be done before SROM treatment is initiated (and why)?

Answer 26

Must have specialist consultation because it is off-label

Question 27

High risk factors for methadone toxicity (overdose)

Answer 27

• older or teens with short period of use / no IVDU
• use benzos, EtOH or other sedatives
• COPD or resp illness
• low tolerance to opioids (use infrequently, small amounts)

Question 28

When to use methadone over bup/nix

Answer 28

• failed bup/nlx (likely highly tolerant or bup/nlx by IV)
• prefers methadone and severely dependentd

Question 29

methadone vs bup/nlx efficacy

Answer 29

Methadone only has advantage to bup/nlx when both are used at low doses

Therefore, start with bup/nlx and get to a good treatment dose

(Mattick et al., 215/2018)- Cochrane review of tx heroin use disorder