Methadone is a low-cost, strong opioid that is increasingly used as a first-line treatment for pain in palliative care (PC). Its long and unpredictable half-life and slow elimination phase can make titration challenging. Evidence for titration modalities is scarce.
To describe the titration phase of the treatment with low-dose first-line methadone and the use of methadone for breakthrough pain.
Prospective study with strong opioid–naïve patients with moderate to severe cancer pain followed at a tertiary PC unit in Argentina. Starting methadone dose was 2.5–5 mg/day every 8, 12, or 24 h. Titration allowed daily dose increases from day 1, and prescription of oral methadone 2.5 mg every 2 h with a maximum of 3 rescue doses/day for breakthrough pain. Pain control, methadone stabilization dose, and adverse effects, among other variables, were daily assessed over the first 7 days (T0–T7).
Sixty-two patients were included. Initial median (IQR) methadone dose was 5 (2.5) mg/day. Pain intensity decreased from a median (IQR) of 8 (2.3) at T0 to 4 (2.3) at T1 and remained ≤ 4 until T7 (all p < 0.0001 compared to T0). Similar results were obtained through the categorical and tolerability scales for pain. Fifty patients (81%) reached pain control, 66% in the first 48 h. Methadone daily doses at T2 and T7 were higher than that at T0: 7.5 (3) and 6.7 (5.5) versus 5 (2.5), respectively (all p < 0.05). The opioid escalation index at T7 was 1.7%. The median (IQR) number of rescues, stabilization dose, and time for stabilization was 0 (1), 5(4.5) mg, and 3(2) days, respectively. Two patients were discontinued due to delirium. All other side effects were mild.
First-line, low-dose methadone using rescue methadone resulted in a pronounced and rapid decrease in pain, with minimal need for titration and for breakthrough doses, and no evidence of accumulation or sedation by the end of the week.
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“Subsidio para la investigación en cáncer de origen nacional 2016-2018”, Instituto Nacional del Cáncer, Argentina.
The study was approved by the Hospital Tornú Ethical Committee, Buenos Aires, Argentina (No. 022/2015).
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All patients gave their informed consent to participate.
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All authors consented for the submission and publication of the manuscript in Supportive Care in Cancer.
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Mammana, G., Bertolino, M., Bruera, E. et al. First-line methadone for cancer pain: titration time analysis. Support Care Cancer (2021). https://doi.org/10.1007/s00520-021-06211-y
- Advanced cancer
- Cancer pain
- First-line methadone