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Ana Rita Pinheiro Barcessat,1,* Marina Nolli Bittencourt,2,* Rebeca Góes Gonçalves,1 Ana Vitoria Goncalves de Oliveira Cruz,1 José Alfredo Coelho Pereira,3 Fabio Augusto Bechelli,4 Arianna Rinaldi3,5 1Health and Biological Sciences Department, Federal University of Amapá, Macapá, Brazil; 2Department of Nursing, Federal University of Mato Grosso, Cuiabá, Brazil; 3Research Department, Rinaldi Fontani Foundation, Florence, Italy; 4International Scientific Society of Neuro Psycho Physical Optimization with REAC Technology, Brazilian Branch, São Paulo, Brazil; 5Department of Neuro Psycho Physio Pathology and Neuro Psycho Physical Optimization, Rinaldi Fontani Institute, Florence, Italy*These authors contributed equally to this workCorrespondence: Arianna RinaldiDepartment of Neuro Psycho Physio Pathology and Neuro Psycho Physical Optimization, Rinaldi Fontani Institute, Florence, ItalyEmail ari@irf.itIntroduction: The purpose of this retrospective study was to compare the effects of two different modalities of administration of the neuro psycho physical optimization (NPPO) neuromodulation treatment, applied with radio electric asymmetric conveyer (REAC) biotechnology devices. Both the modalities are aimed at improving the strategies to deal with and optimize the allostatic response to environmental stressors and exposome. This allows to reduce the dysfunctional adaptive behavior patterns, which underlie many neuropsychological symptoms and pathologies, and to improve the symptoms of depression, anxiety and stress.Materials and Methods: From a population of subjects experiencing at least two of the three symptoms depression, anxiety and stress, the selection of pre and post-treatment Depression, Anxiety, Stress 21 items scale (DASS 21) data was made proceeding with a reverse chronological recruitment mechanism, until reaching 150 subjects for each of the 2 groups. The first group was treated with the neuro psycho physical optimization treatment (NPPO), which is the punctiform modality of administration on the auricle pavilion, and the second group was treated with the neuro psycho physical optimization treatment, which is the area modality of administration applied by the planar probe on the cervicobrachial area (NPPO-CB).Results: The Wilcoxon signs test confirmed the differences in scores in pre and post-treatment DASS-21. The comparison between the two groups data and the comparison across groups data showed that NPPO and NPPO-CB have the same efficacy in reducing the symptoms of depression, anxiety and stress, after a single treatment cycle. Statistical significance was set at p < 0.05.Discussion: This is the first efficacy descriptive comparison between the two different modalities of administration of the NPPO treatment, as different options for the same clinical indication.Keywords: neuromodulation, noninvasive neurostimulation, behavioral disorders, DASS-21