Cubero, D.I., & del Giglio, A. (2010). 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. Supportive Care in Cancer, 18, 235–242.

To evaluate the efficacy of methadone as a substitute for morphine, and to investigate whether the addition of acetaminophen improves pain control in switching to methadone

Patients using morphine for oncologic pain who were on a stable dose for at least one week were recruited. Patients were rapidly switched to oral methadone without a transition period and randomized to receive acetaminophen or placebo with methadone for seven days. The daily morphine dose was converted to methadone in ratios according to the total daily morphine dose. In case of additional pain, patients were instructed to use extra methadone no more than every two hours using a dose equal to 25% of the total daily dose. Use of coanalgesics such as anti-inflammatory drugs, antidepressants, and neuroleptics was allowed. Pain intensity was evaluated daily and recorded by patients in a diary along with all analgesic medications used. Patients were followed for seven days.

• The study reported on 49 patients.
• Median patient age was 58.5 years (range = 19–81 years).
• The sample was 53% male and 47% female.
• Various tumor types were cited, with the most frequent being colorectal, breast, and lung.
• Eighty-eight percent of patients had non-neuropathic pain.
• Median pain intensity at baseline was 5 in the acetaminophen group and 3.5 in the placebo group. Median morphine daily dose at baseline was 60 mg, with a range of 40–540 mg.

• Single site
• Outpatient setting
• Brazil

The study design was double-blind, randomized, placebo-controlled for use of acetaminophen, and open label for switch to methadone.

• Numeric rating scale (0–10)
• Faces pain rating scale
• Four-point rating scale for side effects
• European Organization for Research and Treatment Cancer Core Quality of Life questionnaire (EORTC QLQ-C30)

Of the original study sample, 16% ended participation early due to treatment failure with intense pain, somnolence, or vomiting. Most patients who completed the study had a significant improvement in pain by the faces (p = 0.05) and numeric (p = 0.03) rating scales. There were no differences between patients who did and did not receive acetaminophen.

Study findings show that most patients can be switched from morphine to methadone with no transition period, with some improvement in side effects of constipation and xerostomia and adequate pain control. The addition of acetaminophen in this process was of no benefit.

• The study had a small sample, with less than 100 participants.
• No data were provided on total opioid consumption or use of rescue doses during the study.
• The study period was very short, and even within this time frame, 16% experienced treatment failure with methadone.
• No information was provided on actual use of adjuvant medications for pain control.

This study shows that patients can be rapidly switched from morphine to methadone; however, this approach failed in 16% of patients. Methadone may be associated with less constipation and dry mouth, and may be a good pain control option for patients with these problems. Acetaminophen did not improve pain control with this switching process.