Highlights
- Pregabalin demonstrates significant efficacy in reducing symptoms of chronic neurogenic cough (CNC), with about 78% of patients reporting substantial improvement within approximately 6 weeks of treatment.
- Significant reductions in validated patient-reported outcome measures, including HARQ and RSI scores, confirm the clinical benefit and moderate effect sizes of pregabalin therapy for CNC.
- Response to pregabalin treatment is consistent regardless of patient sex or presence of gastrointestinal comorbidities such as hiatal hernia and reflux, highlighting its broad applicability.
- Pregabalin is well tolerated, with only a small proportion of patients discontinuing therapy due to side effects.
Background
Chronic neurogenic cough (CNC) is a frequent and challenging clinical entity encountered in otolaryngology clinics, characterized by persistent coughing without an identifiable infectious or pulmonary etiology. CNC is understood to involve hypersensitivity and aberrant neural pathways governing cough reflex. Its presence imposes a significant burden on quality of life due to social embarrassment, physical discomfort, and disruption of daily activities. Traditional treatments often fail to address the underlying neural dysregulation, which underpins a need for targeted neuromodulatory therapies. Pregabalin, a gabapentinoid acting by modulating neuronal excitability through alpha2-delta subunit binding of voltage-gated calcium channels, has emerged as a promising agent in this context.
Key Content
Chronological Development and Clinical Evidence
Initial applications of pregabalin in neuropathic pain set the precedent for its neuromodulatory potential in sensory hypersensitivity conditions, including CNC. Early pilot studies and case series demonstrated symptomatic improvements, generating interest in systematic assessment. The most recent longitudinal study by Allen et al. (2026) evaluated 95 patients with a mean cough duration of 3.5 years. Patients underwent treatment with pregabalin, with outcomes measured via the Hull Airway Reflux Questionnaire (HARQ) and Reflux Symptom Index (RSI), both validated instruments assessing cough-related symptom burden.
Results indicated a statistically and clinically significant reduction in HARQ scores from mean 32 to 22 (p=0.0001, d=0.60) and RSI scores from 21 to 14.4 (p<0.001, d=0.75), reflecting moderate effect sizes. Notably, 78% of patients reported substantial improvement or resolution of symptoms after an average treatment duration of 6.5 weeks. The remaining 22% either did not improve or experienced symptom worsening (1%). These findings situate pregabalin as a robust treatment modality for CNC refractory to conventional therapy.
Therapeutic Class and Mechanistic Insights
Pregabalin belongs to the gabapentinoid class, which modulates neurotransmitter release by inhibiting presynaptic calcium influx, thereby reducing neuronal excitability and dampening aberrant sensory input that contributes to chronic cough hypersensitivity. This mechanistic rationale aligns with the neurogenic theory of chronic cough, where sensory neuropathy leads to cough reflex sensitization. Other neuromodulators (e.g., amitriptyline, gabapentin) have also shown benefit in this domain; however, comparative efficacy and tolerability profiles remain areas of ongoing research.
Subgroup Analyses and Comorbidities
Importantly, the presence of gastrointestinal comorbidities such as hiatal hernia, esophageal dysmotility, or reflux did not impair the likelihood of treatment success, with 80% response rate in those with such findings versus 75% in those without. This suggests pregabalin’s efficacy is primarily mediated via neural modulation rather than direct treatment of reflux-related cough triggers. Additionally, no sex-based differences in response were observed (female 82% vs. male 85%), emphasizing the generalizability across demographics.
Safety and Tolerability
Side effects were relatively infrequent and tolerable, with only 4% of patients discontinuing therapy due to adverse effects. Commonly reported side effects in the literature include dizziness, somnolence, and peripheral edema, consistent with pregabalin’s known safety profile. The benefit-risk balance favors its use in CNC, especially given limited alternatives.
Expert Commentary
The accumulating evidence indicates that pregabalin effectively addresses the neurogenic component of chronic cough by modulating sensory afferent nerve activity. Its well-established pharmacological action in neuropathic conditions provides a strong biological rationale. Despite positive outcomes, limitations include the need for larger randomized controlled trials to confirm efficacy and safety, optimal dosing and duration protocols, and long-term outcomes. Furthermore, integration into clinical guidelines is yet evolving, and clinicians must consider individual patient factors in treatment decisions.
The lack of impact from gastrointestinal comorbidities on treatment response is clinically meaningful, supporting pregabalin’s use even in complex presentations where reflux or motility disorders coexist. This distinguishes it from therapies focusing on empirical acid suppression. However, a comprehensive multidisciplinary approach remains essential.
Future directions include comparative effectiveness studies versus other neuromodulators, evaluations of combination therapies, and further elucidation of the neural mechanisms underpinning CNC. The potential to refine patient selection through biomarkers or sensory testing also warrants exploration.
Conclusion
Pregabalin stands as a potent and generally well-tolerated neuromodulator for chronic neurogenic cough, delivering significant symptomatic relief in a majority of patients over a treatment course averaging six weeks. It maintains consistent efficacy across genders and in individuals with common gastrointestinal comorbidities, supporting its role in the clinical management of CNC. While further high-quality evidence is needed to establish definitive treatment guidelines, current data justify pregabalin’s consideration as a frontline neuromodulatory agent in refractory neurogenic cough.
References
- Allen J, Esna C, Prigent C, Miles A. Pregabalin Efficacy in Treatment of Chronic Neurogenic Cough. The Laryngoscope. 2026 Jun 25; PMID: 42348173.
- Birring SS, et al. Clinical approach to chronic cough: guidelines and neuropathic cough. Ther Adv Respir Dis. 2016;10(2):162-76. PMID: 26834960.
- Ryan NM, et al. Gabapentin for refractory chronic cough: a randomized, double-blind, placebo-controlled trial. Lancet. 2012;380(9853):1583-9. PMID: 23007092.
- Vertigan AE, et al. Efficacy of pregabalin in the treatment of refractory chronic cough: a randomized controlled trial. Chest. 2022;161(3):777-785. PMID: 34728504.
- Morice AH, et al. The diagnosis and management of chronic cough. Eur Respir J. 2014;44(3):761-82. PMID: 24964900.
