Edema in a Patient Receiving Methadone for Chronic Low Back Pain
Purpose: The case of a patient who developed edema after receiving methadone for chronic low back pain is reported.
Summary: A 45-year-old white woman developed edema in her lower extremities one week after starting methadone, etodolac, and gabapentin as part of her treatment for chronic low back pain. She was taking methadone as part of her treatment regimen to manage her pain in addition to other agents, including etodolac and gabapentin. After several days on this therapy, she developed edema and stated that she was "feeling drunk." At that time the etodolac and gabapentin were stopped, and the methadone dosage was increased. Several days later, the patient returned to the pain clinic, complaining of continued swelling. The methadone dosage was then decreased, and a diuretic was added to treat the edema; however, her edema did not resolve with the lower dosage of methadone. Methadone was then discontinued, and a fentanyl patch was prescribed. Prednisone was also prescribed, and the dosage of the diuretic was increased. The patient's symptoms resolved, and prednisone was ultimately tapered. The likelihood that the administration of methadone was related to the development of edema in this patient was determined to be probable. There have been a few cases reported in the literature regarding the development of edema with methadone use. In the cases reported, the edema developed after three to six months of methadone therapy.
Conclusion: A patient with chronic low back pain developed edema one week after receiving methadone as part of her pain management regimen.

The pharmacologic treatment of pain must follow the treatment principles of any condition: the correct medication and the proper dosage must be prescribed and the risks and adverse effects must be carefully monitored and weighed against the benefits. The expected adverse effects of medications used to treat chronic pain include excessive sedation, severe constipation, and nausea. If the pain is inadequately relieved, the treatment is considered suboptimal. In such cases, neuropathy may be contributing to the patient's pain, resulting from direct injury to the nerves and nerve tissue. Neuropathic pain sometimes responds to medications that stabilize nerve tissue activity. In some cases, the patient's pain can be relieved by the addition of these medications, which may decrease the amount of opioid required to achieve sustained pain relief.

Methadone, a safe and effective long-acting opioid analgesic, is useful for managing chronic pain. As with other opioids, methadone could be used as part of a comprehensive pain management plan. It should be considered a viable option for pain relief when adequate relief has not been achieved by other pharmacologic and nonpharmacologic modalities. Nonsteroidal anti-inflammatory drugs (NSAIDs) and adjuvant agents to manage neuropathic pain (e.g., tricyclic antidepressants, anticonvulsants) are commonly given in combination with methadone.

Although methadone has gained acceptance for the treatment of moderate to severe pain, a number of authors have cautioned clinicians about the complexities of dosing methadone and have suggested that the drug be prescribed by only practitioners with sufficient experience in an adequately monitored setting. Methadone can be safely used when initial doses are low, conversion ratios are adjusted to the previous opioid dose, and the dosage is slowly adjusted according to the patient's response. General principles of dosing methadone are similar to those of other opioids; however, dosage escalations must be done slowly and cautiously because of the drug's unique pharmacokinetics. Dosage reductions are often warranted when patients experience excessive sedation, primarily due to accumulation of the drug.

Methadone's long half-life is not dependent on a specialized delivery system, as is the case with transdermal fentanyl or sustained-release formulations of morphine and oxycodone. The pharmacokinetic and pharmacodynamic properties of methadone are complex and incompletely documented. Although methadone may have a long elimination half-life (up to 128 hours), the elimination half-life does not necessarily reflect the duration of analgesia. Patients may require methadone administration every 6-8 hours to achieve adequate pain relief, though repeated oral administration of methadone may lead to progressively longer intervals of administration. As a result of the dissociation between half-life and duration of analgesia, methadone can accumulate in the tissue. Patients must be reassessed every few days when methadone is initiated and when the dosage is increased. However, once the dosage is established, follow-up visits can be clinically determined based on specific patient factors. With a 3-day phased conversion from morphine to methadone, the analgesic effects take a median of 5 days (range, 4-13 days) to stabilize.