Low-Dose Morphine Does Not Cause Sleepiness in Chronic Obstructive Pulmonary Disease : A Secondary Analysis of a Randomized Clinical Trial
Altree, Thomas J. ; Toson, Barbara ; Loffler, Kelly A. ; Ekström, Magnus LU
; Currow, David C.
and Eckert, Danny J.
(2024)
In American Journal of Respiratory and Critical Care Medicine
210(9).
p.1113-1122
- Abstract
Rationale: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality, and daytime function have not been rigorously investigated. Objectives: We sought to determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. Methods: We conducted prespecified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained-release morphine versus placebo over 4 weeks commencing at 8 or 16 mg/d with blinded up-titration over 2 weeks to a maximum of 32 mg/d. Primary outcomes for these analyses were Week-1... (More)
Rationale: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality, and daytime function have not been rigorously investigated. Objectives: We sought to determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. Methods: We conducted prespecified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained-release morphine versus placebo over 4 weeks commencing at 8 or 16 mg/d with blinded up-titration over 2 weeks to a maximum of 32 mg/d. Primary outcomes for these analyses were Week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) scores on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire scores (end of Weeks 1 and 4), KSS and ESS scores beyond Week 1, and associations between breathlessness, morphine, and questionnaire scores. Measurements and Main Results: One hundred fifty-six people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (DESS [95% confidence interval] versus placebo: 8-mg group, 20.59 [21.99, 0.81], P = 0.41; 16-mg group, 20.72 [22.33, 0.9], P = 0.38; DKSS vs. placebo, 8-mg group: 0.11 [20.7, 0.9], P = 0.78; 16-mg group, 20.41 [21.31, 0.49], P = 0.37). This neutral effect persisted at later time points. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also showed improvement in LSEQ domain scores including perceived sleep quality and daytime function. Conclusions: Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep.
(Less)
- author
- Altree, Thomas J.
; Toson, Barbara
; Loffler, Kelly A.
; Ekström, Magnus
LU
; Currow, David C.
and Eckert, Danny J.
- organization
- publishing date
- 2024-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- breathlessness, COPD, morphine, opioids, sleep
- in
- American Journal of Respiratory and Critical Care Medicine
- volume
- 210
- issue
- 9
- pages
- 10 pages
- publisher
- American Thoracic Society
- external identifiers
-
- pmid:38477675
- scopus:85205535099
- ISSN
- 1073-449X
- DOI
- 10.1164/rccm.202310-1780OC
- language
- English
- LU publication?
- yes
- id
- a23c9ba5-963a-4332-83a3-26cf0c7969fd
- date added to LUP
- 2025-01-08 15:17:08
- date last changed
- 2025-07-10 06:49:49
@article{a23c9ba5-963a-4332-83a3-26cf0c7969fd,
abstract = {{<p>Rationale: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality, and daytime function have not been rigorously investigated. Objectives: We sought to determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. Methods: We conducted prespecified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained-release morphine versus placebo over 4 weeks commencing at 8 or 16 mg/d with blinded up-titration over 2 weeks to a maximum of 32 mg/d. Primary outcomes for these analyses were Week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) scores on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire scores (end of Weeks 1 and 4), KSS and ESS scores beyond Week 1, and associations between breathlessness, morphine, and questionnaire scores. Measurements and Main Results: One hundred fifty-six people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (DESS [95% confidence interval] versus placebo: 8-mg group, 20.59 [21.99, 0.81], P = 0.41; 16-mg group, 20.72 [22.33, 0.9], P = 0.38; DKSS vs. placebo, 8-mg group: 0.11 [20.7, 0.9], P = 0.78; 16-mg group, 20.41 [21.31, 0.49], P = 0.37). This neutral effect persisted at later time points. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also showed improvement in LSEQ domain scores including perceived sleep quality and daytime function. Conclusions: Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep.</p>}},
author = {{Altree, Thomas J. and Toson, Barbara and Loffler, Kelly A. and Ekström, Magnus and Currow, David C. and Eckert, Danny J.}},
issn = {{1073-449X}},
keywords = {{breathlessness; COPD; morphine; opioids; sleep}},
language = {{eng}},
number = {{9}},
pages = {{1113--1122}},
publisher = {{American Thoracic Society}},
series = {{American Journal of Respiratory and Critical Care Medicine}},
title = {{Low-Dose Morphine Does Not Cause Sleepiness in Chronic Obstructive Pulmonary Disease : A Secondary Analysis of a Randomized Clinical Trial}},
url = {{http://dx.doi.org/10.1164/rccm.202310-1780OC}},
doi = {{10.1164/rccm.202310-1780OC}},
volume = {{210}},
year = {{2024}},
}