Continuous daily histamine-2 (H2) receptor antagonist therapy may have limited utility for laryngopharyngeal reflux (LPR) because its acid-suppressive effect could diminish with repeated dosing.
Investigators reviewed evidence on H2 receptor antagonists in LPR, focusing on pharmacologic tolerance and the role of the agents in contemporary management. They noted that proton pump inhibitors (PPI) remain a common initial treatment for suspected LPR, but H2receptor antagonists are frequently added or used as an alternative when symptoms persist. The investigators evaluated evidence from gastroenterology and otolaryngology literature.
They assessed whether H2receptor antagonists provide durable acid suppression when administered continuously and what role they should have in LPR management. The investigators also considered approaches to persistent symptoms.
Continuous H2receptor antagonist administration leads to tachyphylaxis, with a marked reduction in antisecretory efficacy within days. Data showed loss of acid suppression by about day 5 of continuous treatment, which the investigators attributed to compensatory increases in endogenous histamine release and enterochromaffin-like cell activity. Dose escalation does not overcome the loss of efficacy.
The investigators cited a 2002 study in which the initial benefit of adding a bedtime H2receptor antagonist to PPI therapy for nocturnal acid breakthrough was lost within 1 week. Continued treatment produced no sustained improvement in gastric pH control after 28 days. Contemporary gastroenterology guidance assigns H2receptor antagonists a limited role as daily adjunctive therapy and supports their use primarily on an intermittent or as-needed basis.
Despite the pharmacologic limitations, H2receptor antagonists remain commonly used for suspected LPR in otolaryngology practice. Practice-pattern analyses suggested that laryngology-trained otolaryngologists were more likely to prescribe combination reflux regimens, including concurrent PPI and H2receptor antagonists. Contemporary otolaryngology-specific guidance defining the optimal role and duration of adjunctive H2receptor antagonists remains lacking.
Persistent symptoms may not indicate inadequate acid suppression. The investigators emphasized that LPR is heterogeneous and laryngopharyngeal injury may involve nonacid refluxate components, including pepsin and bile acids or mechanisms unrelated to reflux. These factors may help explain the limited and variable response to acid-targeted therapies among some patients.
Among those with persistent symptoms despite initial acid-suppressive therapy, the investigators favored systematic reassessment rather than indefinite escalation of empiric pharmacologic treatment. Recommended strategies included confirming drug adherence and dosing, reconsidering the working diagnosis, and performing objective reflux testing when clinically appropriate. Hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring can characterize acid and nonacid reflux events and may help individualize treatment decisions.
Other options may be appropriate depending on the patient's symptom profile and reflux phenotype. Alginates may reduce laryngopharyngeal exposure to refluxate through mechanical raft formation and have demonstrated benefit in selected populations. Behavioral or neuromodulatory interventions may be considered when symptoms suggest laryngeal hypersensitivity or functional laryngeal disorders, whereas procedural antireflux interventions may be considered in carefully selected patients with objective evidence of persistent pathologic reflux.
Most data on H2receptor antagonisttachyphylaxis was derived from patients with gastroesophageal reflux disease rather than patients with LPR. The investigators maintained that the pharmacologic phenomenon applies to LPR because the mechanism of acid suppression is identical regardless of the clinical indication. LPR also encompasses heterogeneous mechanisms and variable responses to acid suppression, complicating reliance on prolonged dual acid-suppressive therapy for persistent symptoms.
“Greater alignment of LPR management with contemporary reflux principles, including intermittent rather than continuous H2[receptor agonist] use and phenotype-directed evaluation of persistent symptoms, may improve outcomes for patients with laryngopharyngeal complaints,” wrote lead study author Sophia Linguiti, BA, of Thomas Jefferson University Hospital, and colleagues.
The study authors reported no conflicts of interest.
Source: OTO Open
