First-Line Methadone For Cancer Pain. Titration Time Analysis

Abstract Background. 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.Objective. To describe the titration phase of the treatment with low dose first-line methadone and the use of methadone for breakthrough pain.Methods. 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 hours. Titration allowed daily dose increases from Day 1, and prescription of oral methadone 2.5 mg every 2 hours 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).Results. 62 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 hours. Methadone daily dose 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 were 0 (1), 5(4.5) mg and 3(2) days, respectively. Two patients were discontinued due to delirium. All the other side effects were mild.Conclusions. 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.