Can patients on methadone (Dolophine) experience opioid withdrawal?

From the Guidelines

Yes, patients on methadone can still experience opioid withdrawal symptoms, typically due to insufficient dosing, missed doses, or dose reductions. This is supported by the most recent and highest quality study, which highlights the importance of careful dosing and monitoring to prevent withdrawal symptoms 1. The onset of withdrawal symptoms can vary depending on the half-life of the opioid and the amount consumed, with methadone having a half-life of up to 30 hours.

Key Points to Consider

• Withdrawal symptoms may include anxiety, muscle aches, runny nose, insomnia, sweating, and gastrointestinal distress, which are generally less severe than withdrawal from other opioids but can still be uncomfortable.
• Patients should work closely with their healthcare provider to establish an appropriate methadone dosage, typically starting at 20-30mg daily and adjusting based on individual response.
• The long half-life of methadone means it accumulates in the body over several days, so dose adjustments should be made cautiously, usually no more frequently than every 3-5 days.
• If withdrawal symptoms occur, patients should not self-medicate but contact their healthcare provider immediately for dose adjustment, as methadone works by occupying opioid receptors in the brain, providing a stable level of receptor activation that prevents withdrawal while reducing cravings.

Management of Withdrawal Symptoms

• Treatment of opioid withdrawal may be symptomatic, often involving the use of α2-adrenergic agonists such as clonidine or lofexidine, as well as antiemetics, atypical antipsychotics, and other medications targeting the withdrawal symptoms 1.
• Appropriate use of buprenorphine or methadone can effectively alleviate withdrawal symptoms, and initial dosing may also serve to initiate medication for addiction treatment (MAT) for OUD.
• Methadone clinics have the capability of “split-dosing” methadone, which can be an option for some patients, especially those with chronic pain who are on methadone maintenance for the treatment of opioid use disorder 1.

From the FDA Drug Label

Opioid Antagonists, Mixed Agonist/Antagonists, and Partial Agonists As with other µ-agonists, patients maintained on methadone may experience withdrawal symptoms when given these agents Methadone-maintained patients beginning treatment with above antiretroviral drugs should be monitored for evidence of withdrawal effects and methadone dose should be adjusted accordingly. Methadone-maintained patients beginning treatment with CYP3A4 inducers should be monitored for evidence of withdrawal effects and methadone dose should be adjusted accordingly In patients well-stabilized on methadone, concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms

Patients on methadone (Dolophine) can experience opioid withdrawal, particularly when given certain medications such as:

• Opioid antagonists
• Mixed agonist/antagonists
• Partial agonists
• Certain antiretroviral drugs
• CYP3A4 inducers, such as rifampin, phenytoin, St John’s Wort, phenobarbital, and carbamazepine 2

From the Research

Opioid Withdrawal and Methadone

• Patients on methadone (Dolophine) can experience opioid withdrawal, as evidenced by studies on methadone dosage and withdrawal symptoms 3, 4, 5.
• Inadequate methadone dosage is a risk factor for opioid withdrawal, with a daily starting methadone dose equivalent to 2.5 times the daily fentanyl dose being effective in minimizing withdrawal symptoms 3.
• The rate of withdrawal from methadone maintenance is also important, with a rate of 3% of initial dose per week being recommended to reduce the effects of expectation and withdrawal symptoms 4.
• High-dose methadone can produce superior opioid blockade and comparable withdrawal suppression to lower doses, but may not completely eliminate the effects of heroin 5.
• Clonidine has been used in combination with naltrexone to provide a safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy, with most patients being completely asymptomatic at discharge 6, 7.

Methadone Dosage and Withdrawal

• The optimal dose and efficacy of methadone to prevent withdrawal is still being studied, with some research suggesting that a dose of 80% of the predicted methadone dose is effective in minimizing withdrawal symptoms 3.
• Higher methadone doses may be more effective at reducing heroin use, but may not completely eliminate the effects of heroin 5.
• The use of clonidine and naltrexone in combination has been shown to be a safe and effective treatment for opioid withdrawal, with most patients being able to withdraw completely from methadone therapy within a six-day period 7.