Experimental Drugs for Panic Disorder: An Updated Systematic Review

Experimental Drugs for Panic Disorder: An Updated Systematic Review Abstract: Several effective pharmacological therapies for panic disorder (PD) are available,<br> but they have some drawbacks, and unsatisfactory outcomes can occur. Expanding the<br> variety of anti-panic medications may allow for improving PD treatment. The authors<br> performed an updated systematic review of preclinical and clinical (Phase I–III) pharmacological<br> studies to look for advances made in the last six years concerning novel-mechanismbased<br> anti-panic compounds or using medications approved for nonpsychiatric medical<br> conditions to treat PD. The study included seven published articles presenting a series of<br> preclinical studies, two Phase I clinical studies with orexin receptor (OXR) antagonists, and<br> two clinical studies investigating the effects of D-cycloserine (DCS) and xenon gas in<br> individuals with PD. The latest preclinical findings confirmed and expanded previous<br> promising indications of OXR1 antagonists as novel-mechanism-based anti-panic compounds.<br> Translating preclinical research into clinical applications remains in the early stages.<br> However, limited clinical findings suggested the selective OXR1 antagonist JNJ-61393115<br> may exert anti-panic effects in humans. Overall, OXR1 antagonists displayed a favorable<br> profile of short-term safety and tolerability. Very preliminary suggestions of possible antipanic<br> effects of xenon gas emerged but need confirmation with more rigorous methodology.<br> DCS did not seem promising as an enhancer of cognitive-behavioral therapy in PD. Future<br> studies, including objective panic-related physiological parameters, such as respiratory<br> measures, and expanding the use of panic vulnerability biomarkers, such as hypersensitivity<br> to CO2 panic provocation, may allow for more reliable conclusions about the anti-panic<br> properties of new compounds.