Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. Combination therapy with ibuprofen and methadone for chronic cancer pain. A clinical comparison of the analgesic effects of methadone and morphine administered intramuscularly, and of orally and parenterally administered methadone. Does intravenous methadone provide longer lasting analgesia than intravenous morphine? A randomized, double-blind study. A comparative study of the efficacy and pharmacokinetics of oral methadone and morphine in the treatment of severe pain in patients with cancer. A randomized study on oral administration of morphine and methadone in the treatment of cancer pain. Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.
The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine.
                A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals.
                differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups.
                Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain. This randomized double-blind crossover study compares the narcotic methadone alone with methadone in combination with the peripherally acting, antiprostaglandin agent ibuprofen (Motrin, Upjohn) in 28 patients with moderate to severe cancer-related pain, who were already using a narcotic for pain relief. Results show that the addition of 600 mg of ibuprofen to either 2.5 or 5 mg of methadone significantly increased analgesia, without concomitantly increasing side effects or euphoria. nan A prospective, randomized, double-blind trial was designed to compare the duration of analgesia produced by intravenous morphine and methadone. Patients with intractable cancer-related pain were studied for 5-6 days. One-eighth of the patient's daily opiate requirement was supplied as an i.v. infusion of either morphine or methadone over a period of 15 min. when initiated by the patient using a patient-controlled analgesia device. Dosing intervals, pain intensity assessments and toxicity were evaluated. Twenty-three patients were randomized; 18 were fully evaluable. Ten of the evaluable patients received morphine, 8 received methadone. Dosing intervals did not change over the 5 days for either group. The mean dosing interval for the last 10 doses was 3.9 +/- 0.85 h for patients receiving morphine and 3.9 +/- 1.6 h for patients receiving methadone (P = NS). One patient receiving morphine and one taking methadone required only 2-3 doses/day for pain control. Pain intensity and relief were similar for both groups. All patients had adequate analgesia as determined by at least a 50% difference in pain intensity at peak relief. The duration of pain relief when repeated intravenous doses of these analgesics were given was similar throughout the entire study period although morphine and methadone have different serum half-lives (3 vs. 25 h). Parenteral methadone does not offer a clinically significant increase in the duration of analgesia in patients with severe pain secondary to cancer. Eighteen patients suffering from cancer were entered into a study of the pharmacokinetics and efficacy of methadone and morphine in pain control. All patients had both clinical and radiological evidence of metastatic spread of their cancer and there were no significant differences in age, weight and sites of the primary cancer between the methadone (n = 9) and morphine (n = 9) groups. Blood opioid concentration, visual analogue pain scores (VAPS) and end-tidal percent carbon dioxide were measured before and after both an intravenous and oral dose of either methadone or morphine. Terminal half-lives (mean +/- S.D.) were 30.4 +/- 16.3 h and 2.7 +/- 1.2 h respectively for methadone and morphine while the clearance values (mean +/- S.D.) were 0.19 +/- 0.13 l/min and 1.16 +/- 0.47 l/min. The long half-life of methadone was associated with prolonged pain relief. However, the large variation in the half-life of methadone necessitated careful adjustment of the dosing interval in individual patients. There were pronounced differences in oral bioavailability between the two opioids: methadone, 79 +/- 11.7%, compared to morphine, 26 +/- 13% (mean +/- S.D.). Of greater clinical significance was the variability in these bioavailability estimates with a coefficient of variation of 15% for methadone compared to 50% for morphine. The combined effects of low and variable oral bioavailability for morphine may result in sub-therapeutic doses being administered as practitioners may be inhibited by the size of the effective oral morphine dose and may be confused by the variability in this dose compared to intramuscular doses. The initial oral dose of morphine varied from 15 mg 4 hourly to 150 mg 3 hourly, while the initial dose for methadone varied from 15 mg on alternate nights to 20 mg twice daily. There was no rapid escalation of daily opioid dose for either methadone or morphine when adequate pain control was provided rapidly at the start of treatment by the technique described in this study. nan To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain.
                Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks.
                A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups.
                Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.
The updated review contains new information supporting the previous conclusions that methadone has similar analgesic efficacy to morphine. The additional study examined neuropathic and non-neuropathic pain, finding no superiority for methadone in the former group. The new study also addresses a clinically relevant concern about short term/single dose studies. Use beyond a few days may result in methadone accumulation leading to delayed onset of adverse effects. In an assessment over 28 days there was a higher rate of withdrawal due to side effects in the methadone group. This observation reinforces the advice that experienced clinicians should take responsibility for initiation and careful dose adjustment and monitoring of methadone.