What anxiolytics, apart from benzodiazepines, can be used in a patient with silent reflux (laryngopharyngeal reflux) without exacerbating the condition?

Anxiolytics for Laryngopharyngeal Reflux: Non-Benzodiazepine Options

Buspirone is the preferred anxiolytic for patients with laryngopharyngeal reflux (LPR) because it does not affect GABA binding, lacks the sedative effects that could worsen reflux through lower esophageal sphincter relaxation, and has no significant impact on gastrointestinal motility. 1

Why Benzodiazepines Should Be Avoided in LPR

• Benzodiazepines can worsen reflux by causing lower esophageal sphincter relaxation and reducing esophageal motility, which directly exacerbates the underlying pathophysiology of LPR 2
• The American Geriatrics Society specifically recommends avoiding benzodiazepines in older patients due to risks of cognitive impairment and falls, and these concerns extend to LPR patients who may already have compromised swallowing function 2
• Even single-dose benzodiazepine administration causes psychomotor and cognitive impairment that persists beyond the immediate perioperative period 2

Buspirone: The Optimal Alternative

Buspirone differs fundamentally from benzodiazepines in that it has no significant affinity for benzodiazepine receptors and does not affect GABA binding in vitro or in vivo, meaning it will not cause the muscle relaxation that worsens reflux. 1

Mechanism and Safety Profile

• Buspirone works primarily through high affinity for serotonin (5-HT1A) receptors and moderate affinity for brain D2-dopamine receptors, without the sedative effects associated with typical anxiolytics 1
• It does not exert anticonvulsant or muscle relaxant effects, which is critical because muscle relaxation can compromise esophageal sphincter tone 1
• Buspirone is less sedating than other anxiolytics and does not produce significant functional impairment, though patients should still be cautioned about operating machinery until they know how it affects them 1

Practical Prescribing for LPR Patients

• Start with standard anxiolytic dosing, as buspirone does not require dose adjustment for reflux considerations 1
• Buspirone should be taken consistently either always with or always without food, as food increases AUC and Cmax by 84% and 116% respectively, but this does not worsen reflux—it simply affects drug absorption 1
• The medication undergoes extensive first-pass metabolism with approximately 86% protein binding, and reaches peak plasma levels 40-90 minutes after oral administration 1
• Average elimination half-life is 2-3 hours, requiring multiple daily doses for sustained anxiolytic effect 1

Critical Contraindications and Drug Interactions

• Do not use buspirone with MAOIs or within 14 days of stopping an MAOI due to increased risk of serotonin syndrome and elevated blood pressure 1
• Buspirone is metabolized primarily by CYP3A4, so avoid large amounts of grapefruit juice which can increase drug levels 1
• While buspirone does not increase alcohol-induced impairment in formal studies, concomitant use should be avoided as a prudent measure 1

Alternative Considerations When Buspirone Is Not Suitable

Melatonin as Second-Line Option

• Meta-analysis evidence shows melatonin provides effective preoperative anxiolysis with few side effects compared to placebo, and is equally effective to midazolam for anxiety reduction 2
• Melatonin can be given as tablets or sublingually and may provide both preoperative and postoperative anxiolysis 2
• Melatonin has the additional theoretical benefit of not affecting esophageal sphincter tone or gastrointestinal motility, making it particularly suitable for LPR patients 2

What NOT to Use

• Avoid beta-blockers as anxiolytics in LPR patients, as their adverse side effects can limit use as pre-anxiolytic medications 2
• Do not use opioids for anxiety in LPR patients, as they can cause nausea and potentially worsen reflux symptoms 2
• Neuroleptics such as phenothiazines lack proven evidence for anxiolysis in this context and should not be used 2

Special Consideration: Laryngeal Hypersensitivity

If anxiety symptoms persist despite treating reflux, consider that the patient may have laryngeal hypersensitivity rather than refractory LPR, which would benefit from neuromodulators like gabapentin rather than continued anxiolytic therapy. 3, 4

• After one failed 3-month trial of appropriate LPR therapy, perform objective testing rather than escalating anxiolytic treatment 5, 3
• Laryngeal Recalibration Therapy (LRT) shows 85% symptom response in patients with chronic laryngopharyngeal symptoms regardless of proven GERD on objective testing 3

Common Pitfalls to Avoid

• Do not prescribe benzodiazepines "just for a short course" in LPR patients—even single doses can worsen reflux through sphincter relaxation 2
• Do not assume anxiety is causing the LPR symptoms; anxiety is often a consequence of chronic throat symptoms rather than the cause 5, 6
• Do not continue anxiolytic therapy indefinitely without addressing the underlying LPR through lifestyle modifications, weight loss if BMI >25, head of bed elevation, and avoiding meals within 3 hours of bedtime 5