Gepirone

Chemical identifier CAS number 83928-76-1, is primarily used as a medication to treat major depressive disorder (MDD). It is an azapirone drug, as other drugs in this class act upon the brain’s serotonin receptors. Gepirone is a selective partial agonist at the 5HT_1A receptor, in that it activates this receptor but not fully. This is thought to ease the symptoms of depression and anxiety.

History of Development Approval 

Bristol-Myers Squibb first synthesized gepirone in 1986. It has been tried over many years as a pharmaceutical agent in the treatment of patients with depression and anxiety disorders. The U.S. The Food and Drug Administration (FDA) beat back initial challenges and multiple rejections from the agency based on concerns about gepirone’s effectiveness, until finally approving it for the treatment of major depressive disorder in the United States in September 2023. 

Mechanism of Action 

Gepirone is a partial agonist at the 5-HT_1A receptor and influences brain serotonin activity. Serotonin is a neurotransmitter involved in controlling mood. Gepirone partially stimulates the 5-HT_1A receptors, so it helps balance the levels of serotonin and can thus improve one’s mood and reduce one’s anxiety. Whereas gepirone has limited affinity for dopamine receptors, it is unlike some other antidepressants, and this may lead to a somewhat different side effect profile. 

Pharmacokinetics 

Gepirone is absorbed well after oral administration, with an absolute bioavailability of about 14–17%. 1-PP, 3′-hydroxy gepirone and their hydrates are primary metabolites of olanzapine metabolized by the liver enzyme CYP3A4. The therapeutic effects of the drug are contributed to by these metabolites. Sustained therapeutic levels in the range of 0.5 to 7 ng/ml with less frequent dosing can be achieved with the extended release formulation of gepirone and has a terminal half life of about 5 hours. 

Clinical Uses 

Selected as treatment for adults with major depressive disorder, gepirone is indicated. And clinical trials have shown efficacy reducing depressive symptoms with effect sizes similar to other existing antidepressant drugs. In these studies, gepirone showed much better results than placebo in reducing symptoms. Other uses are used to treat generalized anxiety disorder and hypoactive sexual desire disorder, although these treatments have not yet been approved. 

Dosage and Administration 

This form of gepirone is available in extended release tablet form, 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg. The dose of the specific drug in a given case should be decided by a healthcare professional on the basis of the results of the treatment in a particular case. For this, it’s important not to break the regimen and discontinue the medication without proper consultation from the healthcare professional. 

Side Effects 

Common side effects with gepirone include dizziness, nausea, insomnia, abdominal pain and dyspepsia (indigestion). QT prolongation can occur and may rarely lead to a potentially fatal heart rhythm disorder (torsade de pointes) in people with congenital long QT syndrome, who may be unaware that they have it. Serious side effects include serotonin syndrome, particularly with use of serotonergic drugs. Some adverse effects would require patients to be monitored for and if any concerning symptoms occurred should be reported to a healthcare provider as soon as possible. 

Drug Interactions 

Gepirone is a CYP3A4 metabolite, so drugs that affect CYP3A4 levels of this drug in the body. For example, CYP3A4 inducers such as rifampin or inducers of its activity decrease exposure, and gepirone exposure may increase with strong inhibitors of CYP3A4 such as ketoconazole or verapamil. We would like to inform healthcare providers that we’re taking all medications and to avoid possible interactions. 

Contraindications 

Persons should not take gepirone if they have had a previous allergic reaction to this drug, are taking medications that strongly inhibit CYP3A4, have corrected QT interval >450 milliseconds, have a history of congenital long QT syndrome, have a serious liver problem, or took a monoamine oxidase inhibitor (MAOI) within the past 14 days. These conditions, however, can increase the risk of serious side effects. 

Special Populations 

It is unknown whether gepirone is safe in pregnant or breastfeeding women. Its use in these populations should therefore only be undertaken if the potential benefits are thought to outweigh the risks. Some less proven treatments may be preferred. 

Conclusion 

Approved for treatment of moderate to severe major depressive disorder in adults, the drug gepirone is a selective 5-HT_1A receptor partial agonist. Being a unique drug with a unique mechanism of action and pharmacokinetic profile it is a valuable drug in the management of depression. Like all medications, gepirone should be used by you only under a doctor’s supervision.