Mirtazapine does not alleviate severe breathlessness in COPD, ILD

Treatment with mirtazapine to improve severe breathlessness in patients with chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ILD), or both falls flat, with the use of the medication even associated with adverse reactions, as shown in a phase III study.

The study included 225 adults (median age 74 years, 65.8 percent men) with COPD, ILD, or both, as well as grade 3 or 4 of the modified Medical Research Council breathlessness scale. These patients were randomly assigned to receive oral mirtazapine (n=113) or matching placebo (n=112) for 56 days. Mirtazapine was given at an initial dose of 15 mg before escalating to a maximum of 45 mg per day, tapered at treatment end.

The primary endpoint of worst breathlessness in the preceding 24 h, measured on a 0–10 numerical rating scale (NRS), at 56 days following treatment initiation did not differ between the mirtazapine and placebo groups (difference in adjusted mean NRS score, 0.105, 95 percent CI, –0.407 to 0.618; p=0.69).

“Although the study was underpowered, the primary endpoint effect did not reach the prespecified treatment effect of 0.55 for worst breathlessness score reduction that the study was powered to detect for the primary analysis,” the investigators said.

A total of 215 adverse reactions in 72 of 113 participants (64 percent) in the mirtazapine group vs 116 in 44 of 110 participants (40 percent) in the placebo group were documented. Eleven serious adverse events occurred in six (5 percent) participants in the mirtazapine group and eight serious adverse events in seven (6 percent) participants in the placebo group.

At day 56, three deaths in the mirtazapine group and two in the placebo group were recorded. At day 180, the number of deaths rose to seven in the mirtazapine group and to 11 in the placebo group.