A review of the efficacy and tolerability of immediate-release and extended-release formulations of gepirone

Background: Gepirone, a 5-HT 1A receptor agonist, has been assessed for use in the treatment of anxiety and depressive disorders. Azapirones, including gepirone, act to maintain neurotransmission at 5-HT 1A receptors. Objective: The aim of this article was to review the pharmacology and clinical data for gepirone extended-release (ER) and immediate-release (IR) formulations for the treatment of major depressive disorder (MDD). Methods: Articles were identified by searching MEDLINE (1966 to present) using the search term gepirone. The reference list retrieved was reviewed for relevant clinical articles. Results: Initial placebo-controlled clinical trials demonstrated that gepirone IR improved symptoms of depression; however, the short half-life of gepirone necessitated frequent administration, and high peak plasma concentrations at higher doses were associated with an increased incidence of adverse events. An ER formulation of gepirone reduced peak-to-trough fluctuations in plasma concentration while maintaining total drug exposure similar to that seen with the IR formulation; the evidence further suggested that lower peak plasma concentrations resulted in fewer adverse events. In clinical trials, both formulations significantly improved symptoms of depression. However, by permitting the use of higher doses of gepirone, the ER formulation had better efficacy and was less likely to produce adverse events (eg, lightheadedness, nausea, dizziness). Conclusion: Several clinical trials have suggested that gepirone ER formulations have significant antidepressant effects and better tolerability than gepirone IR formulations when used to treat MDD.