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BACKGROUND Panic disorder is a common and important disease in clinical practice that decreases individual productivity and increases health care use. Treatments comprise medication and cognitive behavioral therapy. However, adverse medication effects and poor treatment compliance mean new therapeutic models are needed. OBJECTIVE We hypothesized that digital therapy for panic disorder may improve panic disorder symptoms and that treatment response would be associated with brain activity changes assessed with functional near-infrared spectroscopy (fNIRS). METHODS Individuals (n=50) with a history of panic attacks were recruited. Symptoms were assessed before and after the use of an app for panic disorder, which in this study was a smartphone-based app for treating the clinical symptoms of panic disorder, panic symptoms, depressive symptoms, and anxiety. The hemodynamics in the frontal cortex during the resting state were measured via fNIRS. The app had 4 parts: diary, education, quest, and serious games. The study trial was approved by the institutional review board of Chung-Ang University Hospital (1041078-202112-HR-349-01) and written informed consent was obtained from all participants. RESULTS The number of participants with improved panic symptoms in the app use group (20/25, 80%) was greater than that in the control group (6/21, 29%; χ21=12.3; P=.005). During treatment, the improvement in the Panic Disorder Severity Scale (PDSS) score in the app use group was greater than that in the control group (F1,44=7.03; P=.01). In the app use group, the total PDSS score declined by 42.5% (mean score 14.3, SD 6.5 at baseline and mean score 7.2, SD 3.6 after the intervention), whereas the PDSS score declined by 14.6% in the control group (mean score 12.4, SD 5.2 at baseline and mean score 9.8, SD 7.9 after the intervention). There were no significant differences in accumulated oxygenated hemoglobin (accHbO2) at baseline between the app use and control groups. During treatment, the reduction in accHbO2 in the right ventrolateral prefrontal cortex (VLPFC; F1,44=8.22; P=.006) and the right orbitofrontal cortex (OFC; F1,44=8.88; P=.005) was greater in the app use than the control group. CONCLUSIONS Apps for panic disorder should effectively reduce symptoms and VLPFC and OFC brain activity in patients with panic disorder. The improvement of panic disorder symptoms was positively correlated with decreased VLPFC and OFC brain activity in the resting state. CLINICALTRIAL Clinical Research Information Service KCT0007280; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=21448
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