Hyperacusis-inducing drug candidates

Hyperacusis is a troubling loudness hypersensitivity disorder occasionally involving pain around ear and face. The neural origins of hyperacusis and conditions that evoke it are poorly understood. To gain insights into the neural mechanisms that might give rise to hyperacusis, a pharmacovigilance analysis was conducted on 3833 case reports in which hyperacusis was listed as a drug-induced adverse event in the United States Food and Drug Administration Adverse Event Reporting System (FAERS). The 10 drug classes ranked by the number of reported hyperacusis cases were selective (1) serotonin reuptake inhibitors (e.g., paroxetine), (2) fluoroquinolone antibiotics (e.g., ciprofloxacin), (3) serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine), (4) benzodiazepines (e.g., clonazepam), (5) anticonvulsant-mood stabilizers (e.g., valproate), (6) central nervous system stimulants, (7) atypical antipsycnotics, (8) corticosteroid/glucocorticoid (e.g., prednisolone), (9) anticonvulsant-GABA analogue (e.g., pregabalin) and (10) anticonvulsants (e.g., topiramate). Approximately 70% of hyperacusis cases were females, possibly due to a reporting bias. The most prevalent comorbidities were headache, photophobia, nausea, fatigue, dizziness, anxiety, insomnia, tinnitus and depression. The mechanisms of action and side effects of the 25 drugs in which hyperacusis was listed as an adverse event are discussed along with study limitations such as correlational analysis. The results provide a foundation for future drug-related research on hyperacusis, including studies in animal models to determining which of these drugs can dose-dependently induce hyperacusis.