Natalie Moryl

Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain

&NA; The successful use of methadone in cancer pain has been supported by numerous case reports and clinical studies. Methadone is usually used as a second or third line opioid medication. As the use of methadone increases we are facing the challenge of converting methadone to other opioids as part of sequential opioid trials. Data on the equianalgesic ratios for the substitution of other opioids for methadone are lacking. We present prospective data on 13 consecutive rotations from methadone to a different opioid. The opioid rotation was followed by escalation of pain and/or severe dysphoria, not controlled by a rapid increase in the dose of the second opioid, in 12 of the 13 patients. Only one patient was successfully maintained on the second opioid after the discontinuation of methadone, while 12 patients required a switch back to methadone. We conclude that opioid rotation from methadone to another opioid is often complicated by worsening pain and dysphoria. These symptoms may not improve despite upward titration of the second opioid. A uniformly accepted conversion ratio for substituting methadone with another opioid is currently not available. More data on the rotation from methadone to other opioids are needed.

Pain in Cancer Survivors

Pain is a common problem in cancer survivors, especially in the first few years after treatment. In the longer term, approximately 5% to 10% of survivors have chronic severe pain that interferes with functioning. The prevalence is much higher in certain subpopulations, such as breast cancer survivors. All cancer treatment modalities have the potential to cause pain. Currently, the approach to managing pain in cancer survivors is similar to that for chronic cancer-related pain, pharmacotherapy being the principal treatment modality. Although it may be appropriate to continue strong opioids in survivors with moderate to severe pain, most pain problems in cancer survivors will not require them. Moreover, because more than 40% of cancer survivors now live longer than 10 years, there is growing concern about the long-term adverse effects of opioids and the risks of misuse, abuse, and overdose in the nonpatient population. As with chronic nonmalignant pain, multimodal interventions that incorporate nonpharmacologic therapies should be part of the treatment strategy for pain in cancer survivors, prescribed with the aim of restoring functionality, not just providing comfort. For patients with complex pain issues, multidisciplinary programs should be used, if available. New or worsening pain in a cancer survivor must be evaluated to determine whether the cause is recurrent disease or a second malignancy. This article focuses on patients with a history of cancer who are beyond the acute diagnosis and treatment phase and on common treatment-related pain etiologies. The benefits and harms of the various pharmacologic and nonpharmacologic options for pain management in this setting are reviewed.

Hypoglycemia during rapid methadone dose escalation.

OBJECTIVES To answer a question whether or not rapid methadone dose increase can be associated with onset of hypoglycemia. This hypothesis is based on the previously reported case reports of hypoglycemia with rapid methadone increase and our clinical experience of a number of cases when symptomatic hypoglycemia during rapid methadone escalation was initially mistaken for methadone overdose. METHODS A retrospective chart review of 59 consecutive opioid-tolerant patients with cancer who received methadone for pain while inpatients in a tertiary cancer center within 1 year was performed. In patients who also had hypoglycemia during the admission, blood glucose levels were analyzed in relationship to the time of methadone titration. Use of steroid, presence of fever, renal insufficiency, and periods of fasting were recorded. RESULTS Eleven patients (19 percent) had hypoglycemia while receiving methadone, of them two patients had at least two episodes of hypoglycemia. In the 11 cases of documented hypoglycemia, mean methadone dose was nearly doubled (92 percent increase) within 2 days before the onset of hypoglycemia. None of the other recorded factors correlated with glucose level in this group of patients. CONCLUSIONS Present report is the first reported series of patients with hypoglycemic episodes associated with rapid methadone dose escalation. Based on our results, a patient who develops unexplained sweating, palpitations, or lethargy during methadone titration may benefit from blood glucose monitoring.

A phase I study of D-methadone in patients with chronic pain.

D-Methadone is the d optical isomer of racemic mixture (DL-methadone) used clinically to treat pain and addiction in the United States. D-Methadone is practically devoid of opioid activity but maintains N-methyl-D-aspartate (NMDA) receptor antagonism. Evidence from extensive preclinical studies suggests that NMDA receptor antagonists attenuate neuronal plasticity, reverse opioid analgesic tolerance, and alleviate chronic pain states. The authors conducted a phase I open label study of D-methadone administered for the first time to patients with chronic pain to determine the safety and tolerability of D-methadone. In addition to their long-term regimen of opioids, the patients received 40 mg of D-methadone twice daily for 12 days. Analgesia and toxicity were recorded by the patients in a daily diary and assessed in clinic on days 1, 8, and 12. Eight patients of the 10 enrolled completed the study. Pain scores on Edmonton Symptom Assessment System (ESAS) did not change between days 1 and 12, but five of eight patients (62.5 percent) characterized D-methadone as moderately or very effective in relieving pain on the Global Assessment for pain. Five of the eight patients (62.5 percent) who completed the study requested to start treatment with commercially available methadone (DL-racemic methadone) after completing the study. D-Methadone at the dose of 40 mg PO Q 12 hours was well tolerated. Perspective: This is the first clinical study of D-methadone in patients suffering from chronic pain. Additional phase I and phase II studies are needed to confirm its safety and analgesic effects. If D-methadone is well tolerated, it is likely to become a useful adjuvant to the treatment of a wide spectrum of pain syndromes.

Patient-Reported Outcomes and Opioid Use by Outpatient Cancer Patients

The Memorial Sloan Kettering Pain Registry contains patient characteristics, treatments, and outcomes for a prospective cohort of 1,534 chronic pain cancer patients who were seen at outpatient pain service clinics. Average pain intensity (Brief Pain Inventory) was reported as mild by 24.6% of patients, moderate by 41.5%, and severe by 33.9%. The patients report of average percent pain relief and health state (EuroQOL 5 dimensions) was inversely related to average pain intensity category, whereas measures of pain interference, number of worst pain locations, and physical and psychological distress were directly related to pain intensity category. Eighty-six percent of patients received an opioid at 1 or more clinic encounters. Regression analysis revealed that male sex or being younger (65 years of age or younger) was associated with a greater likelihood of an opioid ordered. Male sex nearly doubled the likelihood of a higher dose being ordered than female sex. Bivariate analysis found that patients receiving opioids reported significantly more pain relief than no-opioid patients. However, patients receiving opioids had higher pain interference scores, lower index of health state, and more physical distress than no-opioid patients Our results identify the need to consider opioid use and dosage when attempting to understand patient-reported outcomes (PROs) and factors affecting pain management. PERSPECTIVE This report describes the results of the analyses of PROs and patient-related electronic health record data collected under standard of care from cancer patients at outpatient pain management clinics of Anesthesiology and Palliative Care at the Memorial Sloan Kettering Cancer Center. Consideration of sex and age as predictors of opioid use is critical in attempting to understand PROs and their relationship to pain management.