What is Exxua?
Exxua (gepirone hydrochloride) is new antidepressant that was FDA approved on September 22, 2023 for major depressive disorder (MDD). Exxua works slightly differently to other currently available antidepressants which may improve its side effect profile, particularly with regards to having less of an impact on sexual functioning and negligible weight gain.
How does Exxua work?
Exxua (gepirone) has both antidepressant and anxiolytic properties and works in two ways. The first is as a selective partial agonist of 5-HT1A receptors. This receptor is one of the most abundant serotonin receptors in the brain, and the dysfunction of this receptor and reduced 5-HT1A binding is thought to play a major role in the development of depression (MDD). When gepirone binds to 5-HT1A it enhances receptor signaling and serotonergic transmission which helps improve the major symptoms of depression such as persistent feelings of sadness and loss of interest in daily activities. Geprione belongs to the azapirone drug class, which is the same class of medicines as buspirone. However, gepirone is more effective than buspirone at activating 5-HT1A receptors and has a 30- to 50-fold lower affinity for D2 receptors than buspirone. But like buspirone, gepirone metabolizes into 1-(2-pyrimidinyl)piperazine, which is a potent antagonist of the α2-adrenergic receptor.
Gepirone also acts as an antagonist at the 5-HT2A receptor. 5-HT2A receptors are widely distributed in the CNS, especially in regions of the brain essential for learning and cognition, and abnormal 5-HT2A receptor activity is associated with several psychiatric disorders and conditions such as depression, schizophrenia, and drug addiction. 5-HT2A antagonists have antipsychotic and antidepressant properties.
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How is Exxua given?
Exxua is given as an oral extended-release tablet. It is available as 18.2mg, 36.3mg, 54.5mg, and 72.6mg tablets.
What are the side effects of Exxua?
Exxua has been well tolerated in clinical trials with less than 10% of gepirone-treated patients stopping the drug due to side effects.
The most common side effects reported in 5% or more people receiving gepirone were mild and included:
- Dizziness
- Nausea
- Sleeplessness (insomnia)
- Abdominal pain
- Dyspepsia.
Exxua was no more likely than a placebo (an inactive pill) to cause weight gain or drowsiness (sedation). There is also evidence that it does not cause sexual dysfunction.
No serious adverse events were reported.
Manufacturer
Exxua is manufactured and packaged by Mission Pharmacal Company, San Antonio, TX 78230 1355.
References
- Feiger, A. D., Heiser, J. F., Shrivastava, R. K., Weiss, K. J., Smith, W. T., Sitsen, J. M., & Gibertini, M. (2003). Gepirone extended-release: new evidence for efficacy in the treatment of major depressive disorder. The Journal of Clinical Psychiatry, 64(3), 243–249.
- Nonacs, R. Gepirone: A Not-So-New Antidepressant Seeks Approval From the FDA (Again) February 15, 2023. https://mghpsychnews.org/gepirone-antidepressant-seeks-fda-approval/
- Savitz, J., Lucki, I., & Drevets, W. C. (2009). 5-HT(1A) receptor function in major depressive disorder. Progress in neurobiology, 88(1), 17–31. https://doi.org/10.1016/j.p
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