From the Guidelines
Methadone maintenance therapy itself does not directly predispose patients to developing delirium during intercurrent illness. However, several factors related to methadone use can increase delirium risk in certain situations. Methadone's long half-life (24-36 hours) and potential for drug interactions are important considerations when patients on maintenance therapy develop acute illnesses. Methadone is metabolized through the CYP450 enzyme system, particularly CYP3A4, which means medications that inhibit these enzymes (like certain antibiotics, antifungals, and antivirals) can increase methadone levels and potentially contribute to delirium, as noted in studies such as 1.
Some key points to consider in the management of methadone-maintained patients with intercurrent illness include:
- Careful review of medication regimens for potential interactions that could increase methadone levels or contribute to delirium
- Monitoring for signs of both methadone toxicity and withdrawal, as either state can contribute to delirium
- Awareness of the potential for electrolyte imbalances to potentiate methadone's QT-prolonging effects, potentially leading to cardiac complications that might manifest with altered mental status
- The importance of maintaining stable methadone dosing while addressing the acute condition to prevent complications, as supported by guidelines and studies such as 1, which discuss the efficacy of opioid rotation, including switching to methadone, in managing opioid-associated delirium.
In clinical practice, the approach to managing intercurrent illness in patients on methadone maintenance should prioritize minimizing disruptions to the patient's stable methadone regimen while effectively treating the acute condition, taking into account the potential for drug interactions and other factors that could influence methadone levels and contribute to delirium, as discussed in 1 and 1.
From the FDA Drug Label
The potential risks of methadone, including the risk of life-threatening arrhythmias, should be weighed against the risks of discontinuing methadone treatment. In the patient being treated for opiate dependence with methadone maintenance therapy, these risks include a very high likelihood of relapse to illicit drug use following methadone discontinuation
The FDA drug label does not answer the question.
From the Research
Ongoing Methadone Maintenance and Delirium Risk
- Ongoing methadone maintenance may predispose individuals to the development of delirium in intercurrent illness, as evidenced by a study that found methadone-related delirium (MRD) occurred in 14 cases out of 81 patients in methadone maintenance treatment 2.
- MRD precipitants included physician prescribing, drug misuse, and renal-fluid alterations, suggesting that methadone can contribute to the development of delirium in certain situations 2.
- Another study found that coadministration of methadone with other medications, such as dextromethorphan, can increase the risk of delirium due to potential interactions 3.
Methadone Interactions and Delirium Risk
- Methadone can interact with other central nervous system (CNS)-active agents, increasing the risk of delirium and other adverse effects 4.
- Specifically, methadone can increase the plasma levels of certain antidepressant drugs, such as desipramine, and can have synergistic interactions with benzodiazepines, increasing the risk of sedation or respiratory depression 4.
- Methadone can also interact with other medications, such as anticonvulsants, which can decrease methadone levels and precipitate a withdrawal syndrome 4.
Methadone Use in Pain Management and Delirium
- Methadone can be effective in the treatment of refractory pain and terminal delirium in advanced cancer patients, with significant improvements in pain control and cognitive status observed in some studies 5.
- However, the use of methadone in pain management should be carefully monitored, as it can contribute to the development of delirium in certain situations, particularly when used in conjunction with other CNS-active agents 5.