Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double-blind, placebo-controlled study

Abstract

Objectives This study aims to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic dose of methadone and/or to improve the level of pain control in oncologic patients. Patients and methods Fifty patients on stable doses of morphine for 1 week were switched to methadone using a "stop-start" strategy and randomized in a double-blind fashion to receive either acetaminophen (750 mg PO every 6 hours) or placebo for a 7-day period. We collected data regarding level of pain, side effects, and quality of life. Results Substitution of morphine for methadone resulted in a significant reduction in constipation (p<0.001) and xerostomia (p=0.03). There was also an improvement in the numeric pain scale (p=0.03) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 questionnaire. Addition of acetaminophen did not improve pain control or reduce the time of stabilization of analgesia once methadone was introduced. At the end of the study, most patients (70.8%, p=0.001) preferred methadone to morphine. Conclusions Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia, allowing for a comfortable dosing regimen. In this scenario, the association with acetaminophen did not improve pain control or reduce the time to achieve an equianalgesic dose of methadone.

Systematic review and meta‐analysis on non‐opioid analgesics in palliative medicine

“…A further four out of six studies, with a combined patient population of 141, were not able to show a further increase in analgesic effect when 650–1000 mg of acetaminophen (3–5 g/day) was combined with step III opioids . Merely two studies, comprising 50 patients, were able to show a positive effect.…”

“…No differences in side effects were found when acetaminophen was combined with a strong opioid compared with a placebo . A direct comparison of acetaminophen alone vs. butorphanol or acetaminophen + butorphanol showed that only the combined preparation delivered significantly superior analgesia compared with placebo…”

“…We screened 5991 publications, of which 43 met the inclusion criteria after full‐text review ( Figure ) . We excluded 30 studies (Supporting Information, S4).…”

The long and winding road of non steroidal antinflammatory drugs and paracetamol in cancer pain management: A critical review

“…Finally, paracetamol was used to assist opioid switching from morphine to methadone in a randomized, doubleblind, placebo-controlled study [17]. Whatever the reason for switching, possibly uncontrolled pain and/or adverse effects, 50 patients having unfavorable balance between pain and adverse effects, did not changed their analgesic regimen for one week.…”

Methadone versus Fentanyl in Patients with Radiation‐Induced Nociceptive Pain with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial

“…A more recent systematic review, based on 4 RCTs published after the 2007 Cochrane review, showed no difference in effectiveness between methadone compared to other strong opioids in 2 RCTs . Two other RCTs used in this systematic review evaluated the effect of opioid rotation to methadone: in one study no conclusion on the efficacy of methadone in treatment of cancer pain could be presented due to the number of dropouts, and the other reported a decrease in pain intensity switching from morphine to methadone and a patient preference for methadone . It is important to realize that these studies were performed to show superiority instead of noninferiority of one drug over another.…”