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,
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-mechanismbased
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 antipanic
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.