Tachyphylaxis and Dependence in Pharmacotherapy for Unexplained Chronic Cough

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Unexplained chronic cough (UCC) is a perplexing condition treated with neuromodulators. Although previous literature describes the effectiveness of neuromodulators, there is little on the development of tachyphylaxis or dependence to neuromodulators over time. Our objective is to capture the experience of a large cohort of patients with UCC over an extended period, looking for these 2 phenomena.

Study Design

Case series with chart review.


Tertiary care hospital.

Subjects and Methods

We performed a retrospective review of patients diagnosed with UCC from 2010 to 2014. Patient outcomes were measured through percentage improvement scores. Treatment failures were attributed to no benefit, intolerable side effects, or tachyphylaxis. Tachyphylaxis was defined as the need for higher doses of medication following diminishing therapeutic benefit, while dependence was defined as a failure to stop therapy following attempted de-escalation or resurgence following drug cessation.


Sixty-eight patients were included in the study. Tachyphylaxis was observed among 35% of patients while dependence was observed among 27% of successfully treated patients, together effecting >50% of the cohort. Sixty-eight percent of patients ultimately experienced successful treatment with neuromodulators, demonstrating strikingly distinct responses to different neuromodulator drug classes.


Tachyphylaxis and dependence occur frequently during UCC treatment and have a major impact on treatment outcomes. Patients sometimes demonstrate distinct responses to different neuromodulator classes. The majority of patients will experience successful treatment for their cough, although several trials may be required.

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