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Daniela Caldirola,1,2 Alessandra Alciati,1– 3 Francesco Cuniberti,1,2 Giampaolo Perna1,2 1Department of Biomedical Sciences, Humanitas University, Milan, 20090, Italy; 2Department of Clinical Neurosciences, Villa San Benedetto Menni Hospital, Hermanas Hospitalarias, Como, 22032, Italy; 3Humanitas Clinical and Research Center, IRCCS, Milan, Rozzano, 20089, ItalyCorrespondence: Daniela CaldirolaDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan, 20090, ItalyEmail daniela.caldirola@hunimed.euAbstract: Several effective pharmacological therapies for panic disorder (PD) are available, but they have some drawbacks, and unsatisfactory outcomes can occur. Expanding the variety of anti-panic medications may allow for improving PD treatment. The authors performed an updated systematic review of preclinical and clinical (Phase I–III) pharmacological studies to look for advances made in the last six years concerning novel-mechanism-based anti-panic compounds or using medications approved for nonpsychiatric medical conditions to treat PD. The study included seven published articles presenting a series of preclinical studies, two Phase I clinical studies with orexin receptor (OXR) antagonists, and two clinical studies investigating the effects of D-cycloserine (DCS) and xenon gas in individuals with PD. The latest preclinical findings confirmed and expanded previous promising indications of OXR1 antagonists as novel-mechanism-based anti-panic compounds. Translating preclinical research into clinical applications remains in the early stages. However, limited clinical findings suggested the selective OXR1 antagonist JNJ-61393115 may exert anti-panic effects in humans. Overall, OXR1 antagonists displayed a favorable profile of short-term safety and tolerability. Very preliminary suggestions of possible anti-panic effects of xenon gas emerged but need confirmation with more rigorous methodology. DCS did not seem promising as an enhancer of cognitive-behavioral therapy in PD. Future studies, including objective panic-related physiological parameters, such as respiratory measures, and expanding the use of panic vulnerability biomarkers, such as hypersensitivity to CO2 panic provocation, may allow for more reliable conclusions about the anti-panic properties of new compounds.Keywords: novel drug, experimental therapy, orexin, D-cycloserine, xenon gas

Daniela Caldirola1,2, Giampaolo Perna1–41Humanitas University, 20090 Pieve Emanuele, Milan, Italy; 2Department of Clinical Neurosciences, Hermanas Hospitalarias, Villa San Benedetto Menni Hospital, 22032 Albese Con Cassano, Como, Italy; 3Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200 Maastricht, The Netherlands; 4Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, Miami University, Miami, FL 33136 -1015, USAAbstract: Although several treatment options for panic disorder (PD) are available, the best intervention for each individual patient remains uncertain and the use of a more personalized therapeutic approach in PD is required. In clinical practice, clinicians combine general scientific information and personal experience in the decision-making process to choose a tailored treatment for each patient. In this sense, clinicians already use a somehow personalized medicine strategy. However, the influence of their interpretative personal models may lead to bias related to personal convictions, not sufficiently grounded on scientific evidence. Hence, an effort to give some advice based on the science of personalized medicine could have positive effects on clinicians’ decisions. Based on a narrative review of meta-analyses, systematic reviews, and experimental studies, we proposed a first-step attempt of evidence-based personalized therapy for PD. We focused on some phenomenological profiles, encompassing symptoms during/outside panic attacks, related patterns of physiological functions, and some aspects of physical health, which might be worth considering when developing treatment plans for patients with PD. We considered respiratory, cardiac, vestibular, and derealization/depersonalization profiles, with related implications for treatment. Given the extensiveness of the topic, we considered only medications and some somatic interventions. Our proposal should be considered neither exhaustive nor conclusive, as it is meant as a very preliminary step toward a future, robust evidence-based personalized therapy for PD. Clearly much more work is needed to achieve this goal, and recent technological advances, such as wearable devices, big data platforms, and the application of machine learning techniques, may help obtain reliable findings. We believe that combining the efforts of different research groups in this work in progress can lead to largely shared conclusions in the near future.Keywords: pharmacotherapy, somatic, evidence-based, panic

Giampaolo Perna1-3, Silvia Daccò2, Roberta Menotti2, Daniela Caldirola21Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, University of Maastricht, Maastricht, the Netherlands; 2Department of Clinical Neuroscience, San Benedetto Hospital, Hermanas Hospitalarias, Albese con Cassano, Como, Italy; 3Department of Psychiatry and Behavioral Sciences, Leonard M Miller School of Medicine, University of Miami, Miami, FL, USABackground: Although there are controversial issues (the "American view" and the "European view") regarding the construct and definition of agoraphobia (AG), this syndrome is well recognized and it is a burden in the lives of millions of people worldwide. To better clarify the role of drug therapy in AG, the authors summarized and discussed recent evidence on pharmacological treatments, based on clinical trials available from 2000, with the aim of highlighting pharmacotherapies that may improve this complex syndrome.Methods: A systematic review of the literature regarding the pharmacological treatment of AG was carried out using MEDLINE, EBSCO, and Cochrane databases, with keywords individuated by MeSH research. Only randomized, placebo-controlled studies or comparative clinical trials were included.Results: After selection, 25 studies were included. All the selected studies included patients with AG associated with panic disorder. Effective compounds included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, selective noradrenergic reuptake inhibitors, and benzodiazepines. Paroxetine, sertraline, citalopram, escitalopram, and clomipramine showed the most consistent results, while fluvoxamine, fluoxetine, and imipramine showed limited efficacy. Preliminary results suggested the potential efficacy of inositol; D-cycloserine showed mixed results for its ability to improve the outcome of exposure-based cognitive behavioral therapy. More studies with the latter compounds are needed before drawing definitive conclusions.Conclusion: No studies have been specifically oriented toward evaluating the effect of drugs on AG; in the available studies, the improvement of AG might have been the consequence of the reduction of panic attacks. Before developing a "true" psychopharmacology of AG it is crucial to clarify its definition. There may be several potential mechanisms involved, including fear-learning processes, balance system dysfunction, high light sensitivity, and impaired visuospatial abilities, but further studies are warranted.Keywords: panic, anxiety, avoidance, pharmacological treatment, drug therapy

Personalized medicine (PM) aims to establish a new approach in clinical decision-making, based upon a patient's individual profile in order to tailor treatment to each patient's characteristics. Although this has become a focus of the discussion also in the psychiatric field, with evidence of its high potential coming from several proof-of-concept studies, nearly no tools have been developed by now that are ready to be applied in clinical practice. In this paper, we discuss recent technological advances that can make a shift toward a clinical application of the PM paradigm. We focus specifically on those technologies that allow both the collection of massive as much as real-time data, i.e., electronic medical records and smart wearable devices, and to achieve relevant predictions using these data, i.e. the application of machine learning techniques. [ABSTRACT FROM AUTHOR]

Background: Catechol-O-methyltransferase (COMT), one of the enzymes deputed to the inactivation of catecholamines, exists in two allelic variants modulated by a genetic polymorphism: COMT H allele with high activity and [...]