Author Affiliations: Departments of Otolaryngology–Head and Neck Surgery (Drs Piccirillo, Duddy, and Kallogjeri and Ms Nicklaus), Psychiatry (Drs Garcia and Pierce), Anatomy and Neurobiology (Dr Burton), and Radiology (Drs Vlassenko and Mintun), Washington University School of Medicine, and Department of Mathematics, Washington University (Dr Spitznagel), St Louis, Missouri. Dr Garcia is now with the Department of Psychiatry, University of Texas–Southwestern, Austin.
We are writing in response to Folmer's questions and concerns regarding our published results of daily low-frequency rTMS to the left temporoparietal region in patients with chronic bothersome tinnitus. First, Folmer claims that because there is a great deal of variability among patients with tinnitus, our inclusion of “[o ]nly 14 patients” was inadequate to base conclusions regarding the efficacy of rTMS. The inclusion and exclusion criteria ensured that the patients enrolled in our study formed a homogeneous group of severely bothered patients with tinnitus without overt signs and symptoms of depression or other significant medical comorbidities. A homogeneous group of patients with tinnitus was not always created in previous studies. For instance, in the article by Frank et al1 that was cited by Folmer, roughly 30% of the participants had a Beck Depression Inventory score in the depression range (≥14). A smaller, yet still significant, number of patients in the study by Khedr et al2 were depressed. The positive response to rTMS reported in these studies may have been a result of the treatment of depression. Furthermore, the use of a crossover design increased the power of our study to detect a clinically significant difference and, in this respect, partially compensated for the small size. Our decision to terminate the study was not made without careful consideration. The biostatistician who performed the interim analysis demonstrated that if a treatment effect was present, the effect would be no greater than a change of 14 points on the Tinnitus Handicap Inventory, a value well below our a priori selected minimal clinical difference of 20. The inclusion of additional patients would have, at best, allowed us to identify small and clinically nonsignificant effects, while exposing patients with tinnitus to the risk and discomfort (albeit slight) of rTMS. Furthermore, working with the limited budget afforded to us by the National Institutes of Health, we did not feel justified in continuing the enrollment of patients under this research protocol. The results of the interim analysis and the decision to terminate the study were approved by the Washington University Human Research Protection Office, St Louis, Missouri.
Piccirillo JF, Garcia KS, Nicklaus J, Pierce K, Burton H, Vlassenko AG, Mintun M, Duddy D, Kallogjeri D, Spitznagel EL. Repetitive Transcranial Magnetic Stimulation for Tinnitus—Reply. Arch Otolaryngol Head Neck Surg. 2011;137(7):730-732. doi:10.1001/archoto.2011.108