The Subjective Experiences of Ceasing Regular, Low-Dose, Sustained-Release Morphine when Treating Moderate to Severe Chronic Breathlessness

Introduction: Using time-limited trials of low-dose, sustained-release morphine to reduce chronic breathlessness to evaluate net effects may generate opioid withdrawal symptoms if medication is ceased. This sub-study of a larger randomized, placebo-controlled, double-blind trial aimed to evaluate if this occurred.

Methods: People with modified Medical Research Council breathlessness scores of 3 or 4 and chronic obstructive pulmonary disease were eligible for a dose-increment titration phase (≤3weeks) and blinded extension (<26 weeks). Participants filled out the Subjective Opioid Withdrawal Scale (SOWS) daily for three days after ceasing/completing study medication (score 0–60; scores >20/60 severe opioid withdrawal). Active therapy was compared with placebo, and then, for people on morphine, comparisons between higher doses (24 mg, 32 mg), and lower doses (8 mg, 16 mg) and duration were undertaken.

Results: Data were available for 126/156 participants (47% female, median age 73). Placebo or active therapy (Days 1–3) showed no statistically significant differences in SOWS scores (p > 0.05 for all days; Day 1 median 3/60 [IQR 1, 5] compared with 2/60 [IQR 1, 6], respectively; p = 0.475). Neither morphine duration nor dose were significantly different. Two people in the lower dose group in the extension phase had scores >20 for all three days. Individual symptoms that may draw clinical attention to morphine withdrawal include anxiety, a runny nose, perspiration, shaking, hot flushes, or nausea.

Discussion: This preplanned substudy quantified risks of people experiencing self-reported symptoms of opioid withdrawal using a validated tool to inform discussions between clinicians and people with chronic breathlessness.