Epidemiology

• 2.1 million people meet OUD criteria.

Neurobiology

• Opioids are agonists at the mu receptor in the brain. They trigger a reward system that can lead to OUD.

Initial Assessment

• Single question screener: “how many times in the past year have you used an illegal drug or prescription medication for nonmedical reasons?”
• Response of “at least once” is a positive screen, but does not equate OUD.
• Assessment using DSM-V criteria:
• For OUD as opposed to other SUD, must have criteria in addition to tolerance and withdrawal to meet OUD.
  • 6Cs (lost control, unable to cut back, cravings, health consequences, physical consequences, relationship consequences).
  • Significant time obtaining, using, or recovering.
  • Interfered with home/school/work role.
  • Give up other important activities.
  • Increased tolerance.
  • Withdrawal symptoms.
• Severity: 2-3=mild, 4-5=moderate, and ≥6=severe.
• Also ask about:
  • Other substances used.
  • Pattern of use, overdoses, syringe access services for those who inject, injection practices.
  • History of OUD treatment and current OUD goals.
  • Reason for use.
  • Support.
• PMH, past psychiatric history, medication history.
• Physical exam.
• Labs are not required, but recommend UTox, pregnancy testing, LFTs, HIV, hepatitis panel.
• Check CURES (or other PDMP).

Opiate Withdrawal Presentation

Opiate withdrawal is rarely dangerous but is physically uncomfortable/distressing to the patient. It is best to prevent or quickly deal with withdrawal symptoms in the medically ill patient.

Pharmacokinetics

• Heroin withdrawal: begins 12-24 hours after last use, peaks at 2-3 days, lasts 5-7 days.
• Methadone withdrawal: begins 1-3 days after last dose, peaks at 5-7 days, lasts 2-3 weeks.

Signs and symptoms

• Early/mild signs: sweating, yawning, rhinorrhea, dilated pupils, insomnia.
• Late/severe signs: piloerection, vomiting, diarrhea.
• Symptoms: body aches/pains, cramps, nausea, anxiety, opioid cravings.

Management

• Opioid replacement: because of the variability in content of street heroin, empiric dosing is recommended rather than a conversion based on grams or reported daily use.
• Drug of choice is morphine, unless the patient is already in a methadone maintenance program and you can contact the program manager. Methadone carries a serious risk of delayed respiratory arrest due to slow accumulation of drug (long half-life) and steady-state concentrations may not be reached for several days.
• If currently in methadone program (detox or maintenance): verify current dose with case manager. Do NOT give large doses of methadone unless verified first.
• Opioid adjuncts:
• Clonidine (if BP can tolerate) PO or patch can be effective in reducing sympathetic activity (tachycardia, hypertension, piloerection) but does not fully suppress opioid craving. Start with caution in the inpatient setting as patients can develop rebound hypertension if discontinuing on discharge.
• Treat insomnia with zolpidem or benzodiazepines.
• Treat or prevent nicotine withdrawal in smokers.
• Loperamide for diarrhea.
• If not in a program, refer to substance abuse counseling services and outpatient program on discharge.

Evaluation of active withdrawal

• Clinical Opioid Withdrawal Scale (COWS) shortcut: subjective symptoms + 1 objective sign.
• Subjective symptoms: nausea, abdominal pain, myalgias, chills.
• Objective signs: restlessness, sweating, rhinorrhea, dilated pupils, watery eyes, tachycardia, yawning, goose bumps, vomiting, diarrhea, tremor.
• Allow patient to choose primary medication (methadone, buprenorphine) and offer adjunct support. Remember that patients may have opioid deficit and these will not meet acute pain needs.

Primary medications for OUD treatment

• Buprenorphine:
  • Check Utox, pregnancy test, CURES (in CA), LFTs.
  • Ask about last opioid used:
    • If short-acting: wait up to 12 hours before buprenorphine initiation but can start as soon as COWS 8-11.
    • If long acting (e.g. MS Contin): wait 24-48 hours before buprenorphine initiation but can start as soon as COWS 8-11.
    • If methadone: wait 5 days or consult Addiction Care Team (ACT) for gradual buprenorphine uptitration protocol.
    • If cannot have an opioid free period, consult ACT for assistance.
  • Day 1: if COWS >8, give buprenorphine 4-8 mg sublingual (if concerned about precipitated withdrawal, start at 2 mg).
    • 1 hour later, recheck COWS. If >8, give 4 mg more.
    • 6 hours later, recheck COWS. If >8, give 4 mg more.
    • Do not exceed 16 mg on day 1.
  • Day 2: give total day 1 dose in AM.
    • 1 hour later, if having craving, pain, withdrawal give 4-8 mg more.
    • Goal daily dose 16-24 mg.
    • Split into TID dosing if there is concurrent pain.
• Methadone:
• Check Utox, pregnancy test, EKG (to evaluate QTc), CURES (in CA).
• Day 1: give methadone 20 mg.
  • Check COWS q4h. If >8, give 10 mg more. Can repeat for up to 40mg on day 1.
  • Do not exceed 40 mg on day 1.
  • Can give additional short acting opioids if acute pain or continued withdrawal despite methadone.
  • Ensure adjunctive medications are also scheduled.
• Day 2: give total day 1 dose in AM.
  • Check COWS q4h. If >8, give 10 mg more.
  • Do not exceed 50 mg on day 2.
• Day 3: give total day 2 dose in AM.
  • Check COWS q4h. If >8, give 10 mg more.
  • Do not exceed 60 mg on day 3.
• Day 4: give total day 3 dose in AM.
  • If already reached 60 mg daily, continue current dose for 5 days before next 10 mg increase.
  • If <60 mg daily, may give 10 mg to reach 60 mg/day maximum.

Adjunctive support

• For sweating, restlessness, hot flashes, watery eyes, anxiety: clonidine 0.1-0.3 mg PO q6-8h PRN (max 1.2 mg/day).
• For loose stools: loperamide 4 mg PO x1, then 2 mg PRN (max 16 mg/day).
• For nausea: zofran 4 mg PO q6h PRN.
• For insomnia: trazodone 50-100 mg PO qHS PRN, melatonin 3-9 mg PO qHS PRN.
• For anxiety and insomnia: diphenhydramine 25-50 mg PO q8h PRN.
• For pain: tylenol 650 mg PO q6h PRN, ibuprofen 200-800 mg PO q8h PRN.

Medication-Assisted Treatment

Medication	Methadone	Buprenorphine	Extended-Release Naltrexone
Mechanism	Full mu agonist	Partial mu agonist. Comes with naloxone to discourage injecting	Mu antagonist
Adverse effects	Sedation, constipation, hypogonadism, prolonged QT, drug-drug interactions, overdose is possible	Headache, nausea, constipation, insomnia/hypomania in predisposed patients	Injection site reaction, headache, depression, insomnia, increased ALT
Contra-indications	Active sedation, intoxication	Active sedation, intoxication In severe hepatic impairment use buprenorphine monoproduct	Active sedation, intoxication
Effectiveness	Decreases morbidity and mortality, reduced opioid use, HIV transmission, risky behavior; all-cause mortality is 3x higher when methadone is stopped Treatment retention equivalent to high dose buprenorphine	All-cause mortality reduced by 50% Treatment retention (buprenorphine dose > 16 mg) similar to methadone	Similar to buprenorphine but initiation is difficult (XBOT trial) Oral form is ineffective
Treatment locations	Federally certified opioid treatment programs (OTP)	Many: primary care (need x waiver), OTP, SUD clinics	Many: primary care, SUD clinics
Initiation considerations	Must commit to daily OTP visit Do not need to be in withdrawal for initiation	Variable based on patient needs Mild withdrawal required for initiation if recently used opioids	May be seen monthly Complete withdrawal required for initiation
Initiation regimen	See above	See above	380 mg IM q4 weeks
Pain considerations	Full dose should be continued with additional opioid and non-opioid analgesics as needed. In hospital can split into TID dosing but dose must be consolidated by discharge. Cannot be prescribed in setting of OUD as must be obtained by OTP	Full dose should be continued with additional opioid and non-opioid analgesics as needed. Can also increase dose Consider 3x daily dosing	Hold naltrexone if due Opioids will be less effective, use nonopioid analgesics (ketamine, regional block) If opioids needed, use high dose in carefully monitored setting (risk of overdose as naltrexone dissociates)

Who can prescribe buprenorphine and for how long?

• Eligible providers: need DEA X-waiver though in the emergency department and inpatient setting do not need X-waiver!
• DEA x-waiver exceptions:
  • Any licensed provider in any setting can administer buprenorphine to a patient with OUD for up to 3 consecutive days without a DEA waiver (administration is defined as giving medication under observation, as opposed to prescribing).
    • Hospitalized patients can receive buprenorphine during entire hospital course (no 3-day limit).
  • Treating patient for pain: any buprenorphine formulation can be used.
  • Managing withdrawal while facilitating entry into treatment for at most 3 days while patient is under observation.

Who can prescribe methadone and for how long?

• Inpatient providers can order methadone for opioid withdrawal, OUD, or to continue outpatient treatment.
• Inpatient providers CANNOT prescribe methadone for OUD on discharge.

Harm Reduction

• Screening tests:
  • HIV, HCV, RPR, QFT/PPD.
• Offer treatment and prophylaxis:
  • HCV.
  • HIV (PrEP is HIV prophylaxis).
• Offer immunizations:
  • HAV, HBV, Tdap.
• Review safe injection practices: buddy system, clean injection site, inject slowly, use clean needs, don’t share needles.
• Offer information on syringe access programs.
• Provide naloxone at discharge.

Tool for patients to decide if ready to start Medications for OUD (MOUD), which MOUD to start, how to start:

https://mat-decisions-in-recovery.samhsa.gov/

 

Coffa D, Snyder H. OUD: Medical Treatment Options

Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med 2003;348:1786-1795.

Tetrault JM, O’Connor PG. Substance abuse and withdrawal in the critical care setting. Crit Care Clin  2008; 24(4): 767-88.

UCSF OUD, Withdrawal and Linkage to Treatment Pocket Card

https://www.bccsu.ca/wp-content/uploads/2017/06/BC-OUD-Guidelines_June2017.pdf

https://www.chcf.org/wp-content/uploads/2019/08/BuprenorphineOverviewClinicians.pdf