Tinnitus Medical Treatment

• Unilateral Hearing Loss as the Sole Presentation of Extensive Intracranial Epidermoid Cyst: A Case Report
• Case Report: Potential of pharmacological treatment for auditory abnormal sensations with aripiprazole: a report of two cases
• Recent advances on the mechanism of acupuncture in the treatment of subjective tinnitus
• A Position Statement on the Treatment of Hearing Impairment, Focused on Hearing Aids, From the Korean Otological Society Hearing Aid Study Group
• Effectiveness and tolerability of liraglutide as add-on treatment in patients with obesity and high-frequency or chronic migraine: A prospective pilot study
• Objective assessment of tinnitus laterality
• When the Mind Meets the Ear: A Scoping Review on Tinnitus and Clinically Measured Psychiatric Comorbidities
• Hearing Improvement after Radiation Therapy for a Facial Nerve Schwannoma: Report of a Case and Review of Literature

Medical treatment for tinnitus aims to reduce perception, alleviate associated symptoms (anxiety, insomnia, depression), and improve quality of life. No medication has been proven to eliminate tinnitus, but several agents may be used off-label in selected cases.

• Examples: Amitriptyline, Nortriptyline
• Mechanism: Inhibit serotonin and norepinephrine reuptake; sedative and anticholinergic effects
• Indications: Tinnitus with comorbid depression, anxiety, or insomnia
• Caution: Anticholinergic side effects (dry mouth, cognitive slowing); cardiotoxicity in overdose

• Examples: Paroxetine, Sertraline
• Role: May help reduce distress in patients with anxiety or depression
• Evidence: Mixed; not proven to reduce tinnitus loudness
• Adverse effects: Sexual dysfunction, GI symptoms, withdrawal syndrome

• Examples: Clonazepam, Diazepam
• Mechanism: GABA-A receptor agonists → sedation, anxiolysis
• Use: Short-term relief in severe tinnitus-related anxiety or insomnia
• Risks: Dependence, tolerance, cognitive impairment, falls in elderly

• Examples: Gabapentin, Carbamazepine, Topiramate
• Rationale: Modulate neural hyperexcitability
• Evidence: Limited and inconsistent
• Adverse effects: Sedation, dizziness, mood changes

• Melatonin: May improve sleep quality and reduce perception in some patients
• Hydroxyzine: Antihistamine with anxiolytic effects; sometimes used for nocturnal symptoms

• Example: Memantine
• Mechanism: Inhibits glutamatergic excitotoxicity
• Status: Experimental; limited clinical benefit

• Example: Verapamil
• Use: Theoretical benefit in vascular tinnitus; minimal evidence

• Mechanism: Vasoactive and antioxidant properties
• Evidence: Contradictory; not superior to placebo in most trials
• Use with caution: May increase bleeding risk

• No drug currently cures tinnitus
• Most treatments are off-label and based on small studies
• Focus should be on individualized symptom control

In a randomized, double-blind, placebo-controlled clinical trial, Lee et al. aimed to determine the optimal dosing strategies for two pharmacological combinations in tinnitus ¹⁾

⚠️ 1. Sample Size Fallacy

• Nortriptyline–Topiramate Combination group: n = 19
• Verapamil–Paroxetine Combination group: n = 22
• → Far too small to support meaningful dose-response conclusions or subgroup analyses

• No inferential statistics reported for dose comparisons
• No placebo-adjusted outcomes presented in this secondary analysis
• Authors infer “dose optimization” from trends that lack statistical significance

• No rationale for combining drugs with overlapping toxicity (e.g., anticholinergic + cognitive + cardiovascular effects)
• No pharmacokinetic modeling, interaction studies, or tolerability stratification

• ~41–42% reached Minimal Clinically Important Difference in both groups
• No clear placebo differential reported
• MCID is treated as a robust outcome without accounting for variability or regression to the mean

• Claims such as “effective dosing” and “early responders required escalation” are not supported by statistical rigor
• Creates an illusion of clinical utility from exploratory data

• No long-term follow-up
• No safety profile for chronic use of either combination
• No reproducibility due to small sample and lack of confirmatory trials
• No generalizability to real-world tinnitus subtypes

This study provides no reliable evidence to guide dosing of polypharmacy regimens in tinnitus. Its conclusions are based on small samples, descriptive trends, and rhetorical inflation. It is best viewed as a hypothesis-generating exercise — not a clinical recommendation.

Verdict:

• 🔴 *High risk of misinterpretation*
• 🔴 *Methodological rigor: Low*
• 🔴 *Clinical usefulness: Negligible*