Salpeter, S.,R., Buckley, J.,S., & Bruera, E. (2013). The use of very-low-dose methadone for palliative pain control and the prevention of opioid hyperalgesia. Journal of Palliative Medicine, 16, 616–622.

To evaluate the effect of low-dose methadone as the primary long-acting opioid in a hospice setting

Two hundred and forty charts of patients who were admitted to a community-based hospice setting from July 1, 2011–April 1,2012 were reviewed. Patients received short-acting doses of opiates equivalent to 5 mg every four hours as needed. Once two or more doses were needed, 2.5 mg methadone was initiated and titrated up by 2.5 mg increments every four to seven days as needed. Median dose of methadone was 5 mg daily, but max dose was 15 mg. Haloperidol was the most commonly prescribed adjuvant nonopoid medication, with a median dose of 3 mg daily. Pain was assessed during each nursing visit on a 0–10 scale and every time the short-acting opiate dose was used more than two times a day. If patients were on long-acting opiates and their life expectancy was greater than a week, they were offered conversion to methadone. Nonopioid agents were used for pain and other symptoms, with Haldol^® being the primary agent for the purpose of NMDA inhibition. If patients were unresponsive, their pain was assessed by their caregiver.

• N = 103 patients with cancer (236 total patients with and without cancer) 
• MEAN AGE = 75 years in patients with cancer (81 years in patients with and without cancer)
• MALES: 33% in patients with cancer (39% in patients with and without cancer), FEMALES: 67% in patients with cancer (61% in patients with and without cancer)
• KEY DISEASE CHARACTERISTICS: 44% had cancer diagnoses, 56% had noncancer diagnoses
• OTHER KEY SAMPLE CHARACTERISTICS: Evaluated patients admitted for hospice care only

• SITE: Single site 
• SETTING TYPE: Other 
• LOCATION: Community-based hospice service

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Elder care, palliative care

A retrospective review of electronic records in those admitted to a community-based hospice service from July 1, 2011–April 1, 2012. Information was reviewed until patients were discharged from hospice or until April 30, 2012.

• Demographics, medication regimens, and pains scores were extracted from electronic medical records.
• Descriptive statistics were used to summarize results.
• Median and peak pain scores (on a scale of 0–10) were recorded.
• Pain scores greater than 4 were considered moderate to severe.

Two-thirds of patients never reported a score greater than 3 on a 0–10 numeric scale. The median reported score was 2 with a peak pain score of 3, with similar reports looking at cancer versus noncancer groups separately.

Methadone provided good pain control for the majority of patients. Methadone could be used with Haldol in pain control, particularly in circumstances in which patients experience a paradoxical reaction (caused by desensitization because of tolerance) and sensitization of the NMDA pathway responding to opioid receptor stimulation. More controlled trials will need to be conducted to consider this as a first-line treatment for management of pain.

• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Measurement validity/reliability questionable
• Findings not generalizable
• Other limitations/explanation: Other agents used in symptom management could have an effect on reporting or perception of pain. Pain assessment not was not rigorous in this study. This was a retrospective, observational study with no control. This study is not generalizable. Pain was not assessed at baseline for more than half of the patients, causing inability to assess short-term effect.

Methadone is low-cost. Education to providers would be needed because the use of methadone may not be a common practice and conversion may be difficult. Risk of constipation is lower with the use of methadone, which may improve quality of life for those suffering from pain and perhaps lower overall pain. Working with high doses of methadone comes with large risk, so careful consideration should be used when prescribing.