OUD 2 - Treatment

Question 1

Name the psychosocial treatments available for OUD (6)

Answer 1

1. Structured counselling
2. Motivational interviewing
3. Case management and care coordination
4. Psychotherapy
5. CBT
6. Contingency management
   (Psychosocial tx + pharm = more effective than either alone)

Question 2

When treating someone with OUD, what is the bottom line?

Answer 2

Start with the person, not with the medications

Question 3

For OUD, why do we not do withdrawal management alone typically?

Answer 3

Not an effective treatment for OUD. Clinical trials report relapse rates ranging from 53.1-66.7% at 1-month, and 61.1-89.2% at 6-months after withdrawal.

Question 4

Detox can be an important 1st point of contact and a bridge to other treatment options. However, detox alone is associated with what? (5)

Answer 4

Increases in the following:
1. HIV transmission
2. HCV transmission
3. Relapse rates
4. Morbidity
5. Mortality

Question 5

What is the MOA of naltrexone?

Answer 5

Opioid receptor antagonist that blocks the euphoric effects of opioids

Question 6

What are the benefits of naltrexone? (3)

Answer 6

1. Ease of administration
2. No induced tolerance during prolonged treatment
3. No potential for dependence/misuse

Question 7

What is the negative of naltrexone?

Answer 7

Increased risk of overdose for pts who stop treatment and relapse to opioid use due to decreased tolerance
- Mortality 3-7x higher than methadone related mortality

Question 8

What is the only formulation of naltrexone available in Canada?

Answer 8

Oral
- Limited benefit vs. placebo

Question 9

List the withdrawal management (alone) treatments that might be used in an OUD patient (3 +/- 3)

Answer 9

1. Tapered methadone, buprenorphine, or alpha-2 adrenergic agonist
   +/- psychosocial treatment
   +/- residential treatment
   +/- oral naltrexone

Question 10

List the opioid agonist therapies (OAT) that might be used in OUD? (2 +/- another 2)

Answer 10

1. Buprenorphine/naloxone (preferred)
2. Methadone
   +/- psychosocial treatment
   +/- residential treatment

Question 11

What is 1st line treatment for OUD?

Answer 11

Buprenorphine/naloxone (Suboxone)

Question 12

What is 2nd line treatment for OUD?

Answer 12

Methadone

Question 13

What is 3rd line treatment for OUD?

Answer 13

Slow-release oral morphine

Question 14

Dosing of suboxone is based on buprenorphine content. So, what is the role of naloxone in the drug? (4)

Answer 14

To prevent diversion essentially
- Naloxone oral or sublingual is not absorbed
- No effect unless injected
- May negate opiates effects if injected

Question 15

What are the 3 buprenorphine formulations (aside from the SL tab of suboxone)?

Answer 15

1. Patches
   - Indicated for pain
2. Buprenorphine/naloxone buccal films
3. Buprenorphine extended release injection (Sublocade)
   - Indicated for OUD
   - SubQ abdominal monthly injection

Question 16

Remember the car analogy. What categories do methadone, buprenorphine, and naltrexone/naloxone fall into?

Answer 16

1. Methadone (full agonist) = fast car going 100km/hr - same with heroin, morphine, and codeine - not good - exceeds threshold for respiratory depression
2. Buprenorphine (partial agonist) = slow car going 40km/hr - still have an effect but it’s safer
3. Naltrexone/naloxone (antagonist) = dead battery - not experiencing any effects

Question 17

True or False? Buprenorphine quickly dissociates from opioid receptors

Answer 17

False - it slowly dissociates
- The duration of action increases with increased doses
- Labelled max = 24mg/day but dosed up to 32mg/day for some

Question 18

Describe the MOA of buprenorphine? (5)

Answer 18

1. High affinity (strong binding ability) for μ opioid receptor
2. Displaces heroin or other opiates from receptors
3. Occupies receptor and blocks other opiates’ effects
4. Partial agonist at μ opioid receptor
5. Antagonist a kappa and delta opioid receptors

Question 19

What are the benefits of buprenorphine being a partial opioid receptor agonist? (3)

Answer 19

1. Opiate ceiling effects
2. No further opioid effects above a certain dose
3. Safer in overdose

Question 20

What are some common adverse effects of buprenorphine/naloxone? (9)

Answer 20

1. Headache
2. Pain
3. Withdrawal syndrome
4. Constipation
5. Nausea
6. Abdominal pain
7. Insomnia
8. Runny nose
9. Sweating

Question 21

What are some other, less common adverse effects of buprenorphine/naloxone? (10)

Answer 21

1. Flu-like symptoms
2. Muscle aches
3. Tooth disorder
4. Dyspepsia
5. Depression
6. Anxiety
7. Nervousness
8. Somnolence
9. Dizziness
10. Paresthesia

Question 22

What are some buprenorphine/naloxone drug interactions to be aware of? (2)

Answer 22

1. Opioids for analgesia
   - Diminished effect
   - May require reassessment in acute pain
2. Alcohol and benzos
   - Increase risk of respiratory depression

Question 23

What are the advantages of using buprenorphine/naloxone over methadone? (5)

Answer 23

1. Decreased risk of OD
2. Decreased side effects
3. Decreased risk of diversion
4. Decreased drug interactions
5. Milder withdrawal symptoms when discontinued

Question 24

Compare suboxone vs. methadone in terms of treatment retention and decreases in illicit opioid use.

Answer 24

1. At medium/high doses, suboxone does not significantly differ from methadone in terms of treatment retention
2. No difference between suboxone and methadone in decreasing illicit opioid use

Question 25

Suboxone vs. methadone. Which is safer?

Answer 25

Suboxone

Question 26

How would you counsel someone taking a bup/nal sublingual tab? (4 important administration points)

Answer 26

1. Dissolve under tongue 2. May take up to 10 minutes to dissolve 3. Avoid eating + drinking during that time 4. No therapeutic effect if swallowed

Question 27

What is precipitated withdrawal? (3)

Answer 27

1. May occur 30 to 60 min after 1st dose 2. Displaces full opiate agonist from opioid receptors 3. Buprenorphine partially activates receptor compared to full agonists - Overall net ↓ in receptor activation --> withdrawal sxs

Question 28

How can you minimize the risk of precipitated withdrawal? (5)

Answer 28

1. Delay 1st dose until moderate withdrawl - Clinical Opiate Withdrawal Scale above 12 2. Start with low dose 3. Communicate risk 4. Monitor patient 5. Micro-dosing induction

Question 29

COWS score ≥__ is when we do suboxone induction

Answer 29

12

Question 30

Describe how microdosing of bup/nal works (3)

Answer 30

1. Repetitive administration of very small bup doses should not precipitate opioid withdrawal 2. Bup will accumulate at the receptor due to long t1/2 3. Over time, an increasing amount of the full agonist will be replaced by bup at the receptor

Question 31

Go through the Bernese Method of bup/nal microdosing

Answer 31

Day 1: - Bup Dosing = 0.5 mg SL once daily - Methadone Dosing = Full dose Day 2: - Bup Dosing = 0.5 mg SL twice daily - Methadone Dosing = Full dose Day 3: - Bup Dosing = 1 mg SL twice daily - Methadone Dosing = Full dose Day 4: - Bup Dosing = 2 mg SL twice daily - Methadone Dosing = Full dose Day 5: - Bup Dosing = 4 mg SL twice daily - Methadone Dosing = Full dose Day 6: - Bup Dosing = 8 mg SL once daily - Methadone Dosing = Full dose Day 7: - Bup Dosing = 8 mg SL in AM and 4 mg SL in PM - Methadone Dosing = Full dose Day 8: - Bup Dosing = 12 mg SL once daily - Methadone Dosing = Stop

Question 32

When is methadone significantly more effective?

Answer 32

Significantly more effective than non-pharm treatment for treatment retention and suppressed heroin use

Question 33

Compared to suboxone, methadone has potentially better retention rates in those with: (3)

Answer 33

1. Moderate-severe OUD 2. Heroin addiction 3. Long history of OUD

Question 34

When may methadone be considered over suboxone?

Answer 34

In certain pts who are severely unstable and who would be at great risk for harm (e.g., HIV, HCV transmission) if lost to follow up

Question 35

Methadone vs. Suboxone. Which is safer in pregnancy?

Answer 35

Methadone at the moment (although new evidence might be showing Sub is okay)

Question 36

What is the onset, duration, and half-life of methadone?

Answer 36

1. Onset = 0.5-1 hour 2. Duration - Analgesia ~4-8 hours - OAT 22-48 hours 3. T1/2 = 24-36 hours (can accumulate)

Question 37

How is methadone metabolized?

Answer 37

Hepatically by P450 system

Question 38

What are some ADEs of methadone? (10)

Answer 38

1. QT prolongation 2. Somnolence 3. Agitation 4. Mild cognitive dysfunction 5. Hormonal dysfunction 6. Weight gain 7. Nausea 8. Sweating 9. Constipation 10. Tooth decay

Question 39

What are some DIs of methadone? (4)

Answer 39

Numerous and clinically significant - CYP3A4 and 2D6 - Additive QT prolongation - Serotonin syndrome - Additive CNS depression

Question 40

What doses of methadone seem to be most effective/optimal?

Answer 40

- Higher doses (60-120mg/day) more so than lower doses - Most studies suggest doses >80mg/day have optimal outcomes -- Doses >120mg/day may be needed to prevent withdrawal

Question 41

Dosing of methadone should be based off what? (3)

Answer 41

1. Clinical judgement due to differences in metabolism 2. Comorbidities (e.g., liver disease, QT prolongation) 3. Drug interactions

Question 42

How often should methadone dosing be adjusted and why?

Answer 42

Adjust dose no sooner than every 5 days due to long half-life (risk of accumulation)

Question 43

What happens if a person misses their methadone dose? (2)

Answer 43

- Missing 1-2 days of any dose is fine - Missing 3+ days of doses will likely lead to need for adjustment of dose to avoid causing opioid toxicity due to loss of tolerance

Question 44

What are the 2 methadone (Methadose) formulations?

Answer 44

1. 10mg/mL red, cherry-flavored oral concentrate (can be administered undilute) 2. 10mg/mL dye-free, sugar-free, unflavored oral concentrate (dilute using ~100mL of Tang to discourage diversion)

Question 45

How do you calculate the amount of Methadose to dispense in mls? For example, If 90mg of metahdone is prescribed, what would you calculate?

Answer 45

Divide the prescribed dose in mg by the conc of the product 90mg/10mg/mL = x ml x = 9ml of Methadose

Question 46

What is the specialist-led alternative approach to OUD management? (1 +/- 2)

Answer 46

Slow-release oral morphine +/- psychosocial treatment +/- residential treatment

Question 47

What seem to be the benefits of slow-release oral morphine (SROM) compared to methadone? (4)

Answer 47

1. May provide similar benefits to methadone 2. Shorter QTc intervals 3. Decreased heroin cravings 4. Reduced dysthymic symptoms

Question 48

What is the brand name of the slow-release oral morphine that has been studied?

Answer 48

Kadian

Question 49

Individuals with severe OUD who inject opioids may not adequately benefit from oral OAT medications for a variety of reasons. Such as? (4)

Answer 49

1. Cravings despite optimal OAT dosing 2. Unable to reach therapeutic dose 3. Insufficient improvements in health, social functioning, quality of life 4. Opting not to initiate oral OAT

Question 50

What have studies found regarding iOAT? (6)

Answer 50

Individuals that are treatment refractory to methadone, prescription injectable diacetylmorphine, administered under the supervision of a trained HCP in a clinic setting is beneficial in reducing: 1. Illicit opioid use 2. Premature treatment discontinuation 3. Criminal activity 4. Incarceration 5. Mortality 6. Also improves overall health and social functioning

Question 51

Summary of clinical practice guidelines: What are the general considerations to think about for using iOAT?

Answer 51

Individuals with severe OUD who inject opioids and have continued to experience significant health and/or social consequences who have not benefitted from previous attempts at oral OAT, or other circumstances and risks that indicate they may benefit from iOAT.

Question 52

Summary of clinical practice guidelines: Describe eligibility of iOAT

Answer 52

Recommended considerations for eligibility in concert with clinical judgement and precautions

Question 53

Summary of clinical practice guidelines: Medication selection for iOAT

Answer 53

Both hydromorphone and diacetylmorphine are reasonable choices, based on availability, patient choice, and prescriber judgement

Question 54

Summary of clinical practice guidelines: Titration process of iOAT

Answer 54

The titration protocol should be followed

Question 55

Summary of clinical practice guidelines: iOAT pre-injection assessment

Answer 55

Performed by a qualified health professional or other trained staff member supervised by a health professional to ensure the pt is not intoxicated or in any other contraindicated acute clinical condition

Question 56

Summary of clinical practice guidelines: iOAT post-intake assessment

Answer 56

Performed by a qualified health professional or other trained staff memeber supervised by a health professional to ensure safety and attend to dose intolerance or other adverse event

Question 57

Summary of clinical practice guidelines: iOAT co-prescription of oral OAT

Answer 57

Consider co-prescription of slow release oral morphine or methadone to prevent withdrawal and cravings between iOAT doses, particularly overnight

Question 58

Summary of clinical practice guidelines: iOAT missed doses

Answer 58

The short-acting nature of iOAT medications requries adequate supervision for missed doses. Refer to missed doses protocol

Question 59

Summary of clinical practice guidelines: Ongoing substance use while on iOAT

Answer 59

Ongoing substance use while on iOAT may be an indication to intensify treatment, which may include dose increases, transferring to a more intensive model of care, and/or increasing psychosocial and other supports.