A systematic review and meta-analysis found that benzodiazepines alone did not improve dyspnea but that benzodiazepines plus opioids may be effective. These findings were published in the Japanese Journal of Clinical Oncology

Dyspnea, or breathing discomfort, is common among patients with advanced cancers, often refractive to treatment, and negatively affects quality of life.

To evaluate effective interventions for dyspnea, investigators from centers in Japan searched publication databases through September 2019 for studies evaluating treatment strategies for dyspnea in the setting of oncology. Two randomized controlled trials evaluating midazolam and morphine were included.

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The studies comprised 101 and 63 patients with lung, breast, gynecologic, sarcomas, colorectal, or head and neck cancers.

Neither midazolam nor morphine alone were preferred for dyspnea relief (risk ratio [RR], 0.95; 95% CI, 0.47-1.89; I2, 85%; P =.88), somnolence (RR, 0.66; 95% CI, 0.34-1.30; I2, 0%; P =.23), or severe adverse event (RR, 0.78; 95% CI, 0.41-1.51; I2, 0%; P =.47) outcomes.

The combination of midazolam and morphine significantly relieved dyspnea compared with morphine alone (RR, 1.33; 95% CI, 1.02-1.75; P =.04) but had no effect on somnolence (RR, 0.67; 95% CI, 0.30-1.53; P =.35) or severe adverse events (RR, 0.90; 95% CI, 0.47-1.71; P =.74).

The major limitation of this analysis was the lack of data available for inclusion.

“Benzodiazepines alone did not show a significant improvement in dyspnea in cancer patients compared with opioids alone. In contrast, the combination of benzodiazepines and opioids could be considered in patients with dyspnea-related anxiety or in those who have had an insufficient response to opioids or non-pharmacological therapy,” the study authors concluded.


Yasuda S, Sugano K, Matsuda Y, et al. Systematic review and meta-analysis of the efficacy of benzodiazepines for dyspnea in patients with cancer. Jpn J Clin Oncol. Published online ahead of print January 12, 2023. doi:10.1093/jjco/hyac206