Opioid-Related Disorders

Opioid use disorder (OUD) is a problematic pattern of opioid use causing clinically significant impairment or distress, diagnosed using DSM-5-TR criteria over any 12-month period.^[1] It sits alongside two related but distinct presentations covered in this chapter: opioid intoxication/overdose (a medical emergency requiring immediate naloxone and emergency medical services) and opioid withdrawal (uncomfortable but rarely life-threatening on its own, though it is the single biggest driver of relapse and subsequent overdose when a patient's tolerance has already dropped).

Opioid agonist therapy (OAT) — buprenorphine/naloxone or methadone — is the standard of care and is strongly recommended over withdrawal management (detoxification) alone, which carries a high risk of relapse, morbidity, and overdose death once tolerance is lost.^[2] The 2024 update to the Canadian national guideline made a genuine, practice-changing change from the 2018 version: methadone and buprenorphine/naloxone are now equally recommended first-line treatments (previously buprenorphine was preferred whenever feasible), based on evidence that the two are similarly effective, each with a different risk profile clinicians must plan around — higher attrition after the first month with buprenorphine, higher mortality risk in the first month with methadone.^[2] Pharmacists are central to this care: dispensing and (where required) witnessing OAT ingestion, catching missed-dose and interaction risks, and being a frontline source of take-home naloxone and harm reduction supplies.

Complications of untreated OUD include overdose; increased risk of oral, throat, liver, colon, and breast cancers; infections (aspiration pneumonia, cellulitis, tuberculosis, hepatitis B and C, HIV); complications of injection drug use (vasculitis, emboli); psychiatric comorbidity (depression, anxiety); suicide; trauma; sexual dysfunction; poor nutrition; severe constipation; and insomnia/sleep apnea.

Distinguishing overdose from withdrawal at the bedside

• Personal or family history of a substance use disorder.
• Chronic pain managed with prescription opioids, particularly at higher doses or for longer durations.
• Co-occurring mental health conditions — depression, anxiety, post-traumatic stress disorder.
• History of trauma or adverse childhood experiences.
• Concurrent use of alcohol, benzodiazepines, or stimulants.
• Social determinants of health — housing instability, unemployment, involvement with the criminal justice system.
• Prior opioid overdose.
• Recent loss of opioid tolerance — release from a correctional facility, discharge from withdrawal management or residential treatment, or a recent hospitalization without continued opioid agonist therapy.
• Injection drug use.
• Exposure to an unregulated drug supply contaminated with fentanyl or other potent synthetic opioids.

History

• Pattern of opioid use — specific opioid(s), route, amount, frequency, and duration; time and amount of most recent use (critical for timing buprenorphine induction safely).
• Other substance use, including alcohol, benzodiazepines, and stimulants.
• Prior opioid agonist therapy, withdrawal management, or overdose history.
• Mental health history and current symptoms.
• Psychosocial context — housing, employment, social supports, involvement with the justice system.
• Pregnancy status in any patient of childbearing potential.
• Validated screening tools: CAGE-AID (CAGE questions adapted for drug use) and the Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool can structure this history.

Physical examination

Look for signs of current intoxication or withdrawal, injection sites/track marks, and complications (cellulitis, abscess, endocarditis murmurs, signs of aspiration).

Grading withdrawal severity: the Clinical Opiate Withdrawal Scale (COWS)

COWS is an 11-item, clinician-scored tool used to grade the severity of opioid withdrawal and — critically — to help time the first dose of buprenorphine/naloxone so it is not given too early (see Choose Initial Treatment for how the score is used).^[3]

Total score is the sum of all 11 items. 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; over 36 = severe withdrawal. A score over 12 (at least moderate withdrawal) is generally required before giving the first traditional-induction dose of buprenorphine/naloxone.^[3]

Investigations

• Pregnancy test in anyone of childbearing potential.
• CBC, renal and liver function, electrolytes, magnesium, and phosphate.
• Bloodborne pathogen testing — HIV, hepatitis B, hepatitis C.
• Urine drug testing for opioids and other substances (e.g., benzodiazepines); consider fentanyl-specific testing given the contamination of the unregulated drug supply.
• Baseline ECG before starting methadone, given its QTc-prolongation risk, and periodically thereafter with dose escalation or when interacting drugs are added.
• Chest x-ray, CT head, or abdominal imaging only as clinically indicated by history/exam findings — not routinely.

• Engage the patient in opioid agonist therapy aligned with their own goals (cessation or reduction).
• Prevent fatal and non-fatal opioid overdose.
• Treat opioid withdrawal safely without precipitating it.
• Assess and treat medical and psychiatric comorbidities.
• Reduce or eliminate use of unregulated/illicit opioids.
• Retain the patient in treatment — the minimum recommended treatment duration is 12 months, and many patients need long-term or indefinite therapy given high relapse rates even after a year.
• Offer psychosocial support and harm reduction services as part of an integrated continuum of care, without making either a precondition for receiving opioid agonist therapy.
• Prevent vertical transmission of infection and neonatal complications when the patient is pregnant.

Patient-centred, stigma-free engagement

Approach opioid use disorder as a medical condition, not a moral failing. Assess readiness for change and use motivational-interviewing techniques matched to the patient's current stage.

Psychosocial interventions

Offer psychosocial treatments and supports as adjuncts to opioid agonist therapy — psychoeducation, cognitive behavioural therapy, motivational enhancement therapy, relapse-prevention training, trauma-informed therapy, peer/mutual-aid support (e.g., Narcotics Anonymous), and family therapy. Psychosocial treatment should never be made mandatory or used as a barrier to receiving opioid agonist therapy — patients who want medication without a mandated counselling component should still receive it.

Harm reduction principles

Offer harm reduction as part of the continuum of care for every patient, independent of their treatment goals or current substance use status — harm reduction is not contingent on a patient pursuing abstinence.

• Take-home naloxone kits and overdose-response training.
• Provision of sterile drug-use equipment (needles/syringes, other supplies).
• Overdose prevention education — using with someone present, avoiding mixing with other sedatives, starting with a test dose after any period of reduced tolerance.
• Referral to supervised consumption or overdose prevention sites and drug-checking services where locally available.
• Bloodborne pathogen testing and vaccination (hepatitis B) as indicated.

Neonatal opioid withdrawal syndrome (NOWS)

NOWS is neonatal withdrawal from in-utero opioid exposure. Onset is usually 48-72 hours after birth for most opioids and 4-14 days for methadone, and its severity does not correlate with the maternal maintenance dose. Features include a high-pitched cry, irritability, insomnia, hypertonia, tremor, vomiting, diarrhea, feeding problems, sweating, and tachypnea — evaluate for alternative causes (sepsis, hypoglycemia, hypocalcemia) before attributing symptoms to NOWS alone. The modified Finnegan Neonatal Abstinence Scoring System is the most widely used scoring tool, assessed every 2-4 hours in an inpatient setting. Nonpharmacologic care is standard first-line management: rooming-in with parents, swaddling, gentle rocking, frequent small feeds, and a quiet, low-light environment. For moderate-to-severe withdrawal, pharmacologic treatment (an oral opioid such as morphine or methadone) is directed by the inpatient neonatology/pediatric team.

Breastfeeding

Both methadone and buprenorphine are compatible with breastfeeding provided the patient has no other contraindication (e.g., is HIV-negative) and the infant is monitored for sedation and respiratory depression. Methadone transfers into breast milk at a low proportion of the maternal dose; buprenorphine transfer is even lower.

Adolescents

Current national guidance is scoped to adults 18 and older. Adolescents with opioid use disorder need referral to a specialized addiction pediatrics or youth addiction service rather than adult dosing extrapolation.

Older adults

Opioids and benzodiazepines are the prescription drugs most often associated with a substance use disorder in older adults, who are more sensitive to sedation and at higher risk of falls and cognitive impairment. Screen with collateral information from family/caregivers where possible — substance use disorders are commonly underdiagnosed in this group. Opioid agonist therapy remains standard, but use a slower dose-escalation schedule for patients over about 55 years of age.

Hepatic and renal impairment

Methadone is metabolized hepatically and eliminated largely via the gastrointestinal tract, so significant renal impairment does not usually require dose adjustment, but hepatic impairment warrants caution and slower titration. Buprenorphine is also hepatically metabolized (CYP3A4) — use caution and monitor closely in significant hepatic impairment. Naloxone dosing is unchanged in renal or hepatic impairment.

See patients at least weekly during induction and periods of active dose titration (in person or virtually), decreasing frequency as clinical stability is achieved. At every visit, review substance use (patient report and, when indicated, urine drug testing), adequacy of dose control (withdrawal symptoms, cravings, sedation), adherence, and psychosocial stability. For methadone specifically, obtain a baseline ECG and repeat with significant dose escalation or new QTc-prolonging interacting drugs, and have a low threshold to reassess in person if there is any concern about toxicity (peak effect around 3 hours post-dose). Pharmacists dispensing opioid agonist therapy should notify the prescriber of missed doses per provincial regulation — missed-dose protocols determine whether a dose can simply resume or whether re-titration from a lower dose is needed, since tolerance is lost quickly once dosing is interrupted. Reassess and replenish take-home naloxone supply at follow-up visits. Periodically re-screen for bloodborne pathogens if ongoing risk factors are present, and continue to monitor for and treat co-occurring mental health conditions.

1. Confirm the medication is being taken correctly (sublingual technique for buprenorphine/naloxone; witnessed ingestion completed as prescribed) and that doses have not been missed.
2. Reassess dose adequacy — ask specifically about withdrawal symptoms or cravings before the next scheduled dose, which suggest the current dose is too low, and titrate upward per the standard schedule.
3. Screen for ongoing unregulated opioid use with urine drug testing (including fentanyl-specific testing where available) and an open, nonjudgmental conversation.
4. Identify and address contributing factors — untreated pain, an unaddressed psychiatric comorbidity, unstable housing, or ongoing use of other substances.
5. If the current agent is adequately dosed but the patient is still struggling to stay engaged or achieve stability, consider switching between buprenorphine/naloxone and methadone — both are similarly effective, and a different risk/benefit profile may suit the patient better.
6. If first-line agents have genuinely failed or are not tolerated despite adequate dosing and switching, move to slow-release oral morphine as a second-line option under specialist support.
7. Regardless of treatment status or apparent "failure," continue to offer and reinforce access to take-home naloxone and harm reduction services — these are never withdrawn as a consequence of ongoing substance use.

• Offering withdrawal management (detoxification) alone without a plan for ongoing opioid agonist therapy — the single highest-risk error, given the sharp rise in overdose risk once tolerance is lost.
• Starting buprenorphine/naloxone before adequate withdrawal (COWS over 12) without using a validated low-dose (microdosing) protocol instead — precipitates withdrawal.
• Underdosing methadone or buprenorphine/naloxone out of excess caution, leaving the patient in withdrawal and prompting a return to unregulated opioid use, which paradoxically increases overdose risk.
• Treating clonidine as adequate opioid agonist therapy on its own — it is a symptomatic adjunct only and does not address craving or the underlying disorder.
• Failing to offer a take-home naloxone kit at every opioid agonist therapy initiation, and to the patient's household/support contacts.
• Stopping opioid agonist therapy abruptly rather than using a slow, individualized taper when a patient wishes to discontinue.
• Making psychosocial counselling mandatory as a precondition for receiving opioid agonist therapy.
• Missing methadone's QTc-prolongation risk — not obtaining a baseline ECG or checking for interacting drugs before and during dose escalation.
• Attempting to taper or detoxify a pregnant patient with opioid use disorder rather than continuing or initiating opioid agonist therapy.
• Treating a single missed dose the same as a prolonged treatment gap — apply the individualized missed-dose protocol rather than reflexively discontinuing therapy.
• Using the transdermal buprenorphine patch or buccal buprenorphine film — approved for chronic pain, not opioid use disorder — as a substitute for sublingual buprenorphine/naloxone.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Opioid Agonists (Full Agonist)

First-line and second-line long-term maintenance therapy.

Partial Opioid Agonist

First-line maintenance therapy; wider safety margin than full agonists due to a ceiling effect on respiratory depression, but must be started at the right time to avoid precipitated withdrawal.

Opioid Antagonists

Alpha2-Adrenergic Agonist

Symptomatic adjunct only — never a substitute for opioid agonist therapy.

Symptomatic Withdrawal Adjuncts

For breakthrough nausea, diarrhea, and myalgia during induction or withdrawal — adjuncts only, not treatment for the underlying disorder.