Optimal Dosing of Nortriptyline-Topiramate and Verapamil-Paroxetine Combinations in Tinnitus Treatment

To determine effective dose strategies for nortriptyline-topiramate (NT) and verapamil-paroxetine (VP) combinations for tinnitus treatment.

This secondary analysis examined data from an 8-week, randomized, double-blind, placebo-controlled trial (RCT) evaluating treatment outcomes in 41 patients. Tinnitus Functional Index (TFI) scores were used as the primary outcome measure, administered at baseline, Week 4, and Week 8 to assess achievement of minimal clinically important differences (MCID) of 13-point reduction. Descriptive statistics were employed to characterize treatment responses and assess dose-response relationships.

In the NT group (n = 19), 42% of the participants achieved a reduction in TFI scores meeting MCID with a mean dose of 44 ± 12 mg nortriptyline plus 59 ± 16 mg topiramate, all showing greater than 15% improvement. In the VP group (n = 22), 41% reached MCID with a mean of 207 ± 36 mg verapamil plus 28 ± 5 mg paroxetine. Of these, 88.9% showed at least a 15% improvement in TFI. Early responders who achieved MCID by the midpoint of the trial required continued dose escalations due to limited improvement in weekly VAS scores afterward. However, subsequent TFI changes were not statistically significant.

Both NT and VP regimens effectively reduce tinnitus severity in approximately half of the patients at moderate doses within 8 weeks. However, long-term effects may not have been fully captured, particularly among late improvers.