1. Duloxetine is significantly more effective than placebo at reducing refractory chronic cough (RCC) frequency and sensitivity.
Evidence Rating Level: 1 (Excellent)
20%-46% of patients with chronic cough, defined as a cough lasting for more than 8 weeks, have RCC, a persistent cough despite thorough investigation and treatment. RCC and its physical and mental sequelae, including chest pain, emesis, sleep disruption, fatigue, and irritability have a burdensome effect on quality of life. The concept of cough hypersensitivity syndrome, where some patients have an enhanced cough reflex sensitivity, has been shown to be associated with 5-hydroxytryptamine (5-HT) and norepinephrine (NE). Theoretically, duloxetine, a serotonin–norepinephrine reuptake inhibitor (SNRI), may play a role in suppressing cough symptoms. This 11-week, randomized, double-blinded, placebo-controlled clinical trial included 98 patients with RCC, defined as a persistent cough lasting for more than two months, with no abnormalities detected in chest radiology, that remains unresponsive to conventional treatments for cough-related conditions. 49 patients (mean [SD] age, 51.41 [15.70] years; 63.27% female) received duloxetine 20 mg three times daily and 49 patients (mean [SD] age, 47.18 [13.43] years; 69.39% female) received a matching placebo. The mean number of coughs per hour in the duloxetine group (83.96 ± 28.95 to 33.12 ± 22.99) was significantly reduced from that of the placebo group (87.67 ± 31.75 to 80.36 ± 31.75) (p < 0.001). There is a significantly improved Leicester Cough Questionnaire (LCQ) score in the duloxetine group (12.75 ± 2.44 to 14.88 ± 2.45; p < 0.001), whereas no significant difference was seen in the placebo group (12.17 ± 2.64 to 12.81 ± 2.32). However, side effects such as nausea (5, 11.36%), dizziness (7, 15.91%), and somnolence (4, 9.09%) occurred more frequently in the duloxetine group (all P < 0.05). Overall, duloxetine seems to reduce cough frequency and severity, suggesting a potential role in RCC. However, its adverse events may be a barrier to this therapeutic role.
Click here to read this study in BMC Medicine
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