What is the recommended initial methadone dose, titration schedule, maintenance range, monitoring parameters, and take‑home criteria for an adult with opioid use disorder?

Methadone Dosing for Opioid Use Disorder

For adults with opioid use disorder, initiate methadone at 20-30 mg (maximum 40 mg on day 1), titrate cautiously over the first week with dose adjustments no more frequently than every 2-4 hours on day 1 and then every 10-14 days thereafter, target a maintenance dose of 80-120 mg/day, monitor with baseline and follow-up ECGs for QTc prolongation, and provide take-home doses only after demonstrating treatment adherence and stability. 1

Initial Dosing

Starting dose must be administered under supervision when the patient shows withdrawal symptoms but no signs of sedation or intoxication:

• Begin with 20-30 mg as a single observed dose; never exceed 30 mg for the initial dose 1
• If same-day adjustment is needed, wait 2-4 hours for peak levels, then provide an additional 5-10 mg only if withdrawal symptoms persist 1
• Total day 1 dose must not exceed 40 mg 1
• Lower initial doses are required for patients who have not used opioids for more than 5 days due to loss of tolerance 1

Critical safety consideration: Deaths have occurred during early treatment due to cumulative effects over the first several days, as methadone's long half-life (8-59 hours) causes delayed accumulation despite short analgesic duration (4-8 hours) 1

Titration Schedule

Dose adjustments during the first week should be based on withdrawal control at peak activity (2-4 hours post-dose):

• Make cautious increases over the first week of treatment 1
• Steady-state plasma concentrations are not reached until 3-5 days of dosing 1
• After the first week, wait at least 10-14 days between dose increases to allow full effects to manifest 2
• Patients must be educated that the dose will "hold" for longer periods as tissue stores accumulate 1

Avoid the common pitfall of rapid dose escalation: Methadone's peak respiratory depressant effects occur later and persist longer than its analgesic effects, creating risk even in opioid-tolerant patients 1

Maintenance Dosing Range

Target maintenance doses between 80-120 mg/day to achieve optimal outcomes:

• This range typically provides 24-hour suppression of opioid withdrawal symptoms, reduces drug craving, blocks euphoric effects of other opioids, and allows tolerance to sedative effects 1
• Clinical stability is most commonly achieved within this 80-120 mg/day range 1, 3
• Higher doses may be required for some patients, but require more intensive monitoring 1

Monitoring Parameters

Implement comprehensive cardiac and clinical monitoring:

Electrocardiogram Monitoring

• Obtain baseline ECG for all patients before initiating methadone to identify QTc prolongation 4, 5
• Repeat ECG with any dose changes, especially when adding medications that prolong QTc (certain psychotropics, fluconazole, macrolides, potassium-lowering agents) 4, 5
• Absolute contraindication: QTc >500 msec 5
• Relative contraindication: QTc 450-500 msec (requires correction of reversible causes first) 5

Clinical Monitoring

• Monitor closely for signs of intoxication, withdrawal, and respiratory depression during the first 24-48 hours and throughout the first week 2, 1
• Implement urine drug screening to monitor for polysubstance use 2
• Assess for drug-drug interactions that may affect methadone metabolism 4
• Monitor for delayed sedation, which can occur as tissue stores accumulate 6

Special population considerations: Patients with renal or hepatic impairment require more frequent clinical observation and dose adjustment, though methadone is preferred in renal impairment due to fecal excretion 4

Take-Home Criteria

Take-home dosing requires demonstrated stability and adherence:

Contraindications to Take-Home Privileges

• New to or poorly adherent to the opioid treatment program 4, 2
• High baseline methadone dose (>100 mg/day) without established stability 5
• Prolonged QTc intervals on ECG 5
• Active polysubstance use 2
• Missing doses (e.g., missing 2 doses in 3 days demonstrates poor adherence and is a specific contraindication to dose increases or take-home privileges) 2

Requirements for Take-Home Dosing

• Establish treatment adherence through observed dosing initially 2, 7
• Demonstrate clinical stability on a consistent dose 1
• Recent regulatory changes during COVID-19 relaxed some take-home criteria, but individual programs must still assess patient-specific risk 7
• Consider increasing frequency of observed dosing rather than restricting take-homes when adherence concerns arise 2

Special Considerations for Pain Management

For patients already in methadone maintenance who develop pain:

• Split methadone into 6-8 hour doses to lengthen analgesic effects (add 5-10% of current dose for afternoon/evening dosing, total 10-20% increase) 4, 5
• If splitting doses is not feasible due to OTP policy, high baseline dose, prolonged QTc, or poor adherence, add adjuvant medications appropriate to pain type (gabapentin for neuropathic pain, NSAIDs for musculoskeletal pain) 4
• Short-acting opioids like oxycodone IR can be added for breakthrough pain in low-risk patients, but require signed release for information exchange between providers and the OTP, baseline ECG verification, and careful monitoring for respiratory depression 4, 5

Critical Safety Warnings

Methadone should only be prescribed by or in consultation with experienced clinicians due to its complex pharmacology: 4, 6

• High degree of opioid tolerance does not eliminate possibility of methadone overdose 1
• Deaths have been reported during conversion from other high-dose opioids and during treatment initiation 1
• Never alter methadone formulations (e.g., adding thickeners) as this may change absorption and bioavailability, increasing risk of adverse effects 6
• Use commercially available liquid formulations when swallowing difficulties exist 6