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).


CONCLUSIONS
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.
Robinson
Donald S
DS
Worldwide Drug Development, Melbourne, Florida 32940, USA. dsrobmd@aol.com
Sitsen
J M Ad
JM
Gibertini
Michael
M
D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003866:Depressive Disorder / Q000188:drug therapy; D004334:Drug Administration Schedule; D006801:Humans; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000928:Antidepressive Agents; D003692:Delayed-Action Preparations; D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C039979:gepirone