From the Guidelines
Methadone can cause several serious side effects, including respiratory depression, QT interval prolongation, and physical dependence, and should be used with caution and under close medical supervision. The side effects of methadone can be significant, and patients should be aware of the potential risks before starting treatment. Common side effects include constipation, excessive sweating, sedation, dizziness, nausea, and vomiting. More serious side effects may include respiratory depression (especially when starting treatment or increasing doses), QT interval prolongation (which can lead to dangerous heart rhythm problems), hormonal changes causing decreased libido or sexual dysfunction, and sleep-disordered breathing. Methadone can also cause physical dependence, and patients may experience withdrawal symptoms if the medication is stopped abruptly. Some patients report cognitive effects like brain fog or difficulty concentrating.
The side effect profile varies between individuals, with some experiencing minimal issues while others have more significant problems. These effects occur because methadone acts on opioid receptors throughout the body, not just in the brain where it helps manage pain or opioid dependence. According to a study published in 2022 1, methadone has been associated with disproportionate numbers of overdose deaths relative to the frequency with which it is prescribed for pain, and it has complicated pharmacokinetics and pharmacodynamics, including a long and variable half-life and peak respiratory depressant effect occurring later and lasting longer than peak analgesic effect.
Patients taking methadone should be monitored regularly by healthcare providers, especially during dose adjustments, and should report any concerning symptoms promptly. Never adjust your methadone dose without medical supervision, as the medication has a long half-life and can accumulate in the body, potentially leading to overdose. A study published in 2017 1 found that the first four weeks after onset and cessation of methadone treatment are the highest risk periods for mortality, and another study published in 2016 1 noted that methadone should not be the first choice for an ER/LA opioid, and only clinicians who are familiar with methadone’s unique risk profile and who are prepared to educate and closely monitor their patients should consider prescribing methadone for pain.
Key points to consider when prescribing methadone include:
- Methadone should not be the first choice for an ER/LA opioid
- Only clinicians who are familiar with methadone’s unique risk profile and who are prepared to educate and closely monitor their patients should consider prescribing methadone for pain
- Patients taking methadone should be monitored regularly by healthcare providers, especially during dose adjustments
- Methadone can cause physical dependence, and patients may experience withdrawal symptoms if the medication is stopped abruptly
- Methadone has a long half-life and can accumulate in the body, potentially leading to overdose.
From the FDA Drug Label
ADVERSE REACTIONS ... The most frequently observed adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. ... Hematologic and Lymphatic: reversible thrombocytopenia has been described in opioid addicts with chronic hepatitis Metabolic and Nutritional: hypokalemia, hypomagnesemia, weight gain Nervous: agitation, confusion, seizures, disorientation, dysphoria, euphoria, insomnia Respiratory: pulmonary edema Skin and Appendages: pruritis, urticaria, other skin rashes, and rarely, hemorrhagic urticaria Special Senses: visual disturbances Urogenital: antidiuretic effect, amenorrhea, urinary retention or hesitancy, reduced libido and/or potency Maintenance on a Stabilized Dose: ... constipation and sweating often persist.
The side effects of Methadone (Dolophine) include:
- Respiratory depression
- Lightheadedness
- Dizziness
- Sedation
- Nausea
- Vomiting
- Sweating
- Reversible thrombocytopenia
- Hypokalemia
- Hypomagnesemia
- Weight gain
- Agitation
- Confusion
- Seizures
- Disorientation
- Dysphoria
- Euphoria
- Insomnia
- Pulmonary edema
- Pruritis
- Urticaria
- Visual disturbances
- Antidiuretic effect
- Amenorrhea
- Urinary retention or hesitancy
- Reduced libido and/or potency
- Constipation 2
From the Research
Side Effects of Methadone
The side effects of Methadone (Dolophine) are similar to those of morphine, as reported in the study 3. Some of the potential side effects and risks associated with methadone use include:
- Respiratory depression, which can be fatal 4
- Aspiration of vomit 4
- Pulmonary oedema 4
- Bronchopneumonia 4
- Cardiac problems 4
- Renal failure 4
- Accumulation and toxicity due to its long plasma half-life 5, 6, 7
- Clinically significant respiratory depression, particularly when used epidurally 6
Special Considerations
Methadone may be a safe and effective analgesic in patients with renal disease because its metabolites are almost exclusively excreted in the feces 3. However, its use requires careful scheduling and titration due to its unpredictable half-life and potential for accumulation and toxicity 5, 7.
Patient Outcomes
Studies have shown that methadone can be used safely and effectively in hospitalized patients with severe pain, with satisfactory pain relief recorded in more than 85% of patients 6. Additionally, methadone may be an important alternative for cancer patients with pain who have side effects related to the use of other opioids 7.