OUD 2 - Treatment Flashcards
Name the psychosocial treatments available for OUD (6)
- Structured counselling
- Motivational interviewing
- Case management and care coordination
- Psychotherapy
- CBT
- Contingency management
(Psychosocial tx + pharm = more effective than either alone)
When treating someone with OUD, what is the bottom line?
Start with the person, not with the medications
For OUD, why do we not do withdrawal management alone typically?
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.
Detox can be an important 1st point of contact and a bridge to other treatment options. However, detox alone is associated with what? (5)
Increases in the following:
1. HIV transmission
2. HCV transmission
3. Relapse rates
4. Morbidity
5. Mortality
What is the MOA of naltrexone?
Opioid receptor antagonist that blocks the euphoric effects of opioids
What are the benefits of naltrexone? (3)
- Ease of administration
- No induced tolerance during prolonged treatment
- No potential for dependence/misuse
What is the negative of naltrexone?
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
What is the only formulation of naltrexone available in Canada?
Oral
- Limited benefit vs. placebo
List the withdrawal management (alone) treatments that might be used in an OUD patient (3 +/- 3)
- Tapered methadone, buprenorphine, or alpha-2 adrenergic agonist
+/- psychosocial treatment
+/- residential treatment
+/- oral naltrexone
List the opioid agonist therapies (OAT) that might be used in OUD? (2 +/- another 2)
- Buprenorphine/naloxone (preferred)
- Methadone
+/- psychosocial treatment
+/- residential treatment
What is 1st line treatment for OUD?
Buprenorphine/naloxone (Suboxone)
What is 2nd line treatment for OUD?
Methadone
What is 3rd line treatment for OUD?
Slow-release oral morphine
Dosing of suboxone is based on buprenorphine content. So, what is the role of naloxone in the drug? (4)
To prevent diversion essentially
- Naloxone oral or sublingual is not absorbed
- No effect unless injected
- May negate opiates effects if injected
What are the 3 buprenorphine formulations (aside from the SL tab of suboxone)?
- Patches
- Indicated for pain - Buprenorphine/naloxone buccal films
- Buprenorphine extended release injection (Sublocade)
- Indicated for OUD
- SubQ abdominal monthly injection
Remember the car analogy. What categories do methadone, buprenorphine, and naltrexone/naloxone fall into?
- Methadone (full agonist) = fast car going 100km/hr - same with heroin, morphine, and codeine - not good - exceeds threshold for respiratory depression
- Buprenorphine (partial agonist) = slow car going 40km/hr - still have an effect but it’s safer
- Naltrexone/naloxone (antagonist) = dead battery - not experiencing any effects
True or False? Buprenorphine quickly dissociates from opioid receptors
False - it slowly dissociates
- The duration of action increases with increased doses
- Labelled max = 24mg/day but dosed up to 32mg/day for some
Describe the MOA of buprenorphine? (5)
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
What are the benefits of buprenorphine being a partial opioid receptor agonist? (3)
- Opiate ceiling effects
- No further opioid effects above a certain dose
- Safer in overdose
What are some common adverse effects of buprenorphine/naloxone? (9)
- Headache
- Pain
- Withdrawal syndrome
- Constipation
- Nausea
- Abdominal pain
- Insomnia
- Runny nose
- Sweating
What are some other, less common adverse effects of buprenorphine/naloxone? (10)
- Flu-like symptoms
- Muscle aches
- Tooth disorder
- Dyspepsia
- Depression
- Anxiety
- Nervousness
- Somnolence
- Dizziness
- Paresthesia
What are some buprenorphine/naloxone drug interactions to be aware of? (2)
- Opioids for analgesia
- Diminished effect
- May require reassessment in acute pain - Alcohol and benzos
- Increase risk of respiratory depression
What are the advantages of using buprenorphine/naloxone over methadone? (5)
- Decreased risk of OD
- Decreased side effects
- Decreased risk of diversion
- Decreased drug interactions
- Milder withdrawal symptoms when discontinued
Compare suboxone vs. methadone in terms of treatment retention and decreases in illicit opioid use.
- At medium/high doses, suboxone does not significantly differ from methadone in terms of treatment retention
- No difference between suboxone and methadone in decreasing illicit opioid use
Suboxone vs. methadone. Which is safer?
Suboxone
How would you counsel someone taking a bup/nal sublingual tab? (4 important administration points)
- Dissolve under tongue
- May take up to 10 minutes to dissolve
- Avoid eating + drinking during that time
- No therapeutic effect if swallowed
What is precipitated withdrawal? (3)
- May occur 30 to 60 min after 1st dose
- Displaces full opiate agonist from opioid receptors
- Buprenorphine partially activates receptor compared to full agonists
- Overall net ↓ in receptor activation –> withdrawal sxs
How can you minimize the risk of precipitated withdrawal? (5)
- Delay 1st dose until moderate withdrawl
- Clinical Opiate Withdrawal Scale above 12 - Start with low dose
- Communicate risk
- Monitor patient
- Micro-dosing induction
COWS score ≥__ is when we do suboxone induction
12
Describe how microdosing of bup/nal works (3)
- Repetitive administration of very small bup doses should not precipitate opioid withdrawal
- Bup will accumulate at the receptor due to long t1/2
- Over time, an increasing amount of the full agonist will be replaced by bup at the receptor
Go through the Bernese Method of bup/nal microdosing
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
When is methadone significantly more effective?
Significantly more effective than non-pharm treatment for treatment retention and suppressed heroin use
Compared to suboxone, methadone has potentially better retention rates in those with: (3)
- Moderate-severe OUD
- Heroin addiction
- Long history of OUD
When may methadone be considered over suboxone?
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
Methadone vs. Suboxone. Which is safer in pregnancy?
Methadone at the moment (although new evidence might be showing Sub is okay)
What is the onset, duration, and half-life of methadone?
- Onset = 0.5-1 hour
- Duration
- Analgesia ~4-8 hours
- OAT 22-48 hours - T1/2 = 24-36 hours (can accumulate)
How is methadone metabolized?
Hepatically by P450 system
What are some ADEs of methadone? (10)
- QT prolongation
- Somnolence
- Agitation
- Mild cognitive dysfunction
- Hormonal dysfunction
- Weight gain
- Nausea
- Sweating
- Constipation
- Tooth decay
What are some DIs of methadone? (4)
Numerous and clinically significant
- CYP3A4 and 2D6
- Additive QT prolongation
- Serotonin syndrome
- Additive CNS depression
What doses of methadone seem to be most effective/optimal?
- 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
Dosing of methadone should be based off what? (3)
- Clinical judgement due to differences in metabolism
- Comorbidities (e.g., liver disease, QT prolongation)
- Drug interactions
How often should methadone dosing be adjusted and why?
Adjust dose no sooner than every 5 days due to long half-life (risk of accumulation)
What happens if a person misses their methadone dose? (2)
- 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
What are the 2 methadone (Methadose) formulations?
- 10mg/mL red, cherry-flavored oral concentrate (can be administered undilute)
- 10mg/mL dye-free, sugar-free, unflavored oral concentrate (dilute using ~100mL of Tang to discourage diversion)
How do you calculate the amount of Methadose to dispense in mls?
For example, If 90mg of metahdone is prescribed, what would you calculate?
Divide the prescribed dose in mg by the conc of the product
90mg/10mg/mL = x ml
x = 9ml of Methadose
What is the specialist-led alternative approach to OUD management? (1 +/- 2)
Slow-release oral morphine
+/- psychosocial treatment
+/- residential treatment
What seem to be the benefits of slow-release oral morphine (SROM) compared to methadone? (4)
- May provide similar benefits to methadone
- Shorter QTc intervals
- Decreased heroin cravings
- Reduced dysthymic symptoms
What is the brand name of the slow-release oral morphine that has been studied?
Kadian
Individuals with severe OUD who inject opioids may not adequately benefit from oral OAT medications for a variety of reasons. Such as? (4)
- Cravings despite optimal OAT dosing
- Unable to reach therapeutic dose
- Insufficient improvements in health, social functioning, quality of life
- Opting not to initiate oral OAT
What have studies found regarding iOAT? (6)
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
Summary of clinical practice guidelines:
What are the general considerations to think about for using iOAT?
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.
Summary of clinical practice guidelines:
Describe eligibility of iOAT
Recommended considerations for eligibility in concert with clinical judgement and precautions
Summary of clinical practice guidelines:
Medication selection for iOAT
Both hydromorphone and diacetylmorphine are reasonable choices, based on availability, patient choice, and prescriber judgement
Summary of clinical practice guidelines:
Titration process of iOAT
The titration protocol should be followed
Summary of clinical practice guidelines:
iOAT pre-injection assessment
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
Summary of clinical practice guidelines:
iOAT post-intake assessment
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
Summary of clinical practice guidelines:
iOAT co-prescription of oral OAT
Consider co-prescription of slow release oral morphine or methadone to prevent withdrawal and cravings between iOAT doses, particularly overnight
Summary of clinical practice guidelines:
iOAT missed doses
The short-acting nature of iOAT medications requries adequate supervision for missed doses. Refer to missed doses protocol
Summary of clinical practice guidelines:
Ongoing substance use while on iOAT
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.
