Low Dose, Controlled Release Morphine Alleviates Cough in Idiopathic Pulmonary Fibrosis

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These data suggest the promise of morphine for cough among those with idiopathic pulmonary fibrosis, though longer term research may be necessary.

Lower dose, controlled-release morphine can help to alleviate coughing among patients that have idiopathic pulmonary fibrosis, according to recent findings.1

These new findings were the results of a recent study looking at patients with idiopathic pulmonary fibrosis treatment for cough, given that there are no current treatments available for the condition.

This research was led by Zhe Wu, MD, from the National Heart and Lung Institute at Imperial College, London, UK. Wu and colleagues acknowledged that, prior to this study, evidence-based options for treatment of idiopathic pulmonary fibrosis had been essentially nonexistent.2

“To evaluate the efficacy and safety of low dose controlled-release morphine as an antitussive therapy in patients with IPF, we did a placebo-controlled, two-way crossover trial,” Wu and colleagues wrote.

Background and Findings

Study participants were required by the investigators to be 40 - 90 years of age and have a diagnosis of idiopathic pulmonary fibrosis within the previous 5 years in order to be eligible. Additionally, they had to have reported having persistent coughs over the course of more than 8 weeks to be recruited for the study, as well as having a score on the cough visual analogue scale (VAS) of 30 mm or more.

The research team conducted their research and it was known as the PACIFY COUGH study, a phase 2 clinical trial carried out through 3 specialized centers found in the UK. The team implemented a randomized, double-blinded, placebo-controlled, and two-way crossover design.

The investigators randomly-assigned the subjects (1:1) to either be placed in the twice-per-day placebo cohort or the twice-per-day controlled-release morphine (5 mg orally) treatment cohort. This would be carried out over the course of a 14-day timeframe, followed later by crossover following a 7-day period of washout.

The team decided upon their study’s morphine and placebo administration sequence through the use of a computer-generated schedule, using blinding for subjects, for investigators, for study nurses, and for pharmacy personnel.

The investigators’ main endpoint they would assess was the percentage change in the objective frequency of awake cough (measured as coughs per hour) from the point of baseline. This was examined through utilization of objective digital monitoring of coughing by day 14 of treatment within the intention-to-treat cohort, made up of all randomized individuals.

The safety data would be assessed in study participants who had taken a minimum of a single study drug and did not end up withdrawing their consent over this period.

After an evaluation of eligibility period from December 2020 - March 2023, 44 subjects were enrolled in the team’s research and randomly assigned to each cohort. Average ages among patients were shown to be 71 years, with 70% of them being reported as male.

Moderately impaired lung function was seen among the participants. The team noted that 43 participants completed the treatment with morphine, and 41 ended up completing the placebo treatment.

Within the investigators’ intention-to-treat analysis, it was noted that morphine led to a 39.4% reduction (95% CI –54.4 to –19.4; P=0.0005) in the objective awake cough frequency. This contrasted with that of those in the placebo arm.

Mean daytime cough frequency was also reported by the team to have decreased from 21.6 coughs per hour at the point of baseline to 12.8 coughs per hour in the morphine arm. This contrasted with the numbers of those in the placebo arm, in which cough rates remained unaltered (21.5 coughs per hour to 20.6 coughs per hour).

Adherence to treatment in the study was identified as 98% among subjects in the treatment cohort and 98% in the placebo cohort. The investigators found that adverse events were seen by 40% of 43 subjects in the morphine arm and 14% of 42 subjects in the placebo arm.

Lastly, the investigators reported that the primary side-effects of the treatment included nausea (14% of 43 individuals) and constipation (21% of 43). They added that a single serious adverse event of death was observed among the placebo cohort.

“Treatment with low dose controlled-release morphine significantly improved objective and subjective cough measures in patients with IPF-associated cough,” they wrote. “Given the negative effects of cough in individuals with IPF, these findings merit its short-term use in clinical practice. Longer term studies should be the focus of future research.”


  1. Z Wu, L Spencer, et al. Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial. The Lancet. January 15, 2024. Date accessed: January 20, 2024.
  2. Chung KF, Birring SS, Morice AH, et al. Tackling the neuropathic cough of idiopathic pulmonary fibrosis (IPF): more needs to be done. Lung. 2022; 200: 673-675.