Experimental Drugs for Panic Disorder: An Updated Systematic Review

Abstract

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 [email protected]: 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

Keywords

• novel drug
• experimental therapy
• orexin
• d-cycloserine
• xenon gas