Although methadone and suboxone (buprenorphine/naloxone) have tremendous benefits in the management of opioid use disorder, unfamiliarity with these treatments can make any clinician uncomfortable and can lead to substandard care for these patients. This summary will shed some light around the basics of methadone and suboxone, as well as give an approach to four key ED encounters with the patient on Opioid Substitution Therapy (OST): withdrawal, acute pain, overdose and pregnancy.
Main effect is through Mu opioid receptor agonism, with non-competitive NMDA antagonism mitigating opioid induced tolerance
A 2009 Cochrane review showed benefit in retention of treatment and suppression of heroin use compared to no treatment
Tolerance to different effects occurs at different rates (fastest to euphoria, least to respiratory depression) and similarly to warfarin, it interacts with numerous other medications
Tolerance can be lost as quickly as a few days without a dose
Slow titration to maintenance dose must occur due to prolonged half-life and risk of respiratory depression
License to prescribed methadone is restricted, but a temporary exemption can be given to physicians to continue usual OST prescription for admitted patients
- Suboxone is a combination of buprenorphine (mainly a partial Mu agonist, but also kappa, delta, and anti-nociceptive properties) and naloxoneto prevent diversion
- A 2014 Cochrane review showed buprenorphine was superior to placebo for retention of treatment; this was directly proportional to dosing
- Ceiling effect of Mu activity mitigates risk of respiratory depression
- Initiation must be started in state of moderate-severe withdrawal (Clinical Opiate Withdrawal Score ≥ 12) to prevent precipitated withdrawal, but can be easily and quickly titrated to desired effect
- Does not require restricted license to prescribe.
Ask for carry doses, and allow patients to take carries if they have them on hand
If not, prescribe their usual dose – this process differs slightly depending on whether it is suboxone or methadone. For both, you should confirm their dose with their usual pharmacy, notify the pharmacy you will be dispensing today’s dose, and prescribe a one time, observed dose in the ED.
- Prescribing OST in Ontario:
- Suboxone: There are no prescription restrictions.
- Methadone: Staff, fellow or designated pharmacist must obtain temporary exemption by calling, faxing, or sending an encrypted email to the Office of Controlled Substances the following information:
- Physician’s name and CPSO number
- Patient’s name
- Dose of methadone
- Indication for temporary license (maintenance for opioid dependence or pain control)
- Date of dose needed
- Usual prescriber’s name in the community if known.
- Dispensing should not be delayed awaiting for approval
- Pharmacist can help facilitate the process
Acute Treatment of Withdrawal: below is a table summarizing the key pharmacotherapies to address various withdrawal related symptoms:
- An interesting alternative to the above treatments is buprenorphine, or suboxone, which has been shown in a Cochrane Review by Gowinget al to be effective in treating withdrawal, and with a better side effect profile compared to clonidine
- Reassurance that their pain will be addressed and that their addiction will not be an obstacle
- Utilizing the WHO ladder stepwise approachto pain
- Progress to opioids if warranted and in discussion with your patient (quick titration, knowing they will require higher doses and/or shorter frequency, address opioids as a possible trigger)
- Utilize adjuvant medications and interventions, such as ketamine, clonidine and local techniques
- Limit opioids to few days (3-5) upon dischargewith further prescriptions to be discussed with their usual OST provider, write it to be dispensed with their OST, consider faxing the record of treatment to their usual OST provider to prevent repercussions of a positive urine drug screen
Methadone has greater mortality when compared to suboxone in the overdose setting.
Two main causes of methadone related mortality are arrhythmias (Torsade de Pointes – TdP) and respiratory depression
High risk periods include recent initiation, recent termination, concomitant benzodiazepine prescriptions. Other risk factors have been delineated in the review article by Modesto-Lowe et al:
Modesto-Lowe, V., Brooks, D., & Petry, N. (2010). Methadone Deaths: Risk Factors in Pain and Addicted Populations. Journal of General Internal Medicine, 25(4), 305–309.
Methadone interacts with numerous medications and has narrow therapeutic window
Early signs of toxicity include inability to maintain a conversation (“nodding off”) and ataxia
Regarding TdP, a QTc>500 or methadone dose >100mg is significant
Suboxone is generally considered the safer alternative, given its ceiling effect, but monitoring for respiratory depression and other symptoms should still occur in the context of an overdose.
Patients with hepatic disease, pediatric patients, and the utilization of other medications that can precipitant serotonin syndrome, all represent populations would be considered higher risk and should monitored closely.
The most important goal with pregnancy and OST is to prevent withdrawal, given there is greater risk to the mother and fetus with repeated episodes of withdrawal.
Methadone, which is currently the only OST supported by the evidence for use in pregnancy, is rapidly metabolized in the third trimester, which can lead to early withdrawal.
Suboxone Start in the ED
Although OST has been shown to have numerous benefits, there still remains significant barriers to its initiation, specifically lack of access and significant wait times for these services.
Given that the ED is often the sole and quickest medical contact for this population, initiation of OST from the ED could address these barriers, specifically suboxone, given its quick titration and favourable safety profile.
A study by D’Onofrio et al supported this, showing that if suboxone was initiated from an ED encounter, patients were more likely to remain in addictions treatment (78%) compared to those simply referred to addiction treatment programs (37%), or those receiving a brief intervention in the department (45%).
The Ottawa Hospital (TOH) is in the process of developing a similar protocol and approach, as summarized below:
- For TOH Staff — To access RAAM (Rapid Access Addiction Medicine) Clinic:
- Provide location, hours and phone number of clinic to patient: 221 Nelson St. in the Sandy Hill Community Health Centre, (613) 569-3488, fax referral not required
- Seen within 7 days via two options: walk-ins on Thursdays and Fridays, or by appointment
- Indications: Opioid or alcohol addiction interested in pharmacologic treatment
- Not chronic opioid prescription