gepirone

Gepirone is a novel investigational drug for the treatment of major depressive disorder, pending FDA approval. Gepirone is a drug belonging to the azapirone class of drugs, similar to buspirone. Gepirone showed a combination of antidepressant, anti-anxiety (anxiolytic) and libido-enhancing properties in clinical trials. Gepirone works by enhancing the levels of serotonin (5-HT1A), an important neurotransmitter in the brain. Impaired serotonin functioning is known to be implicated in anxiety and depression in many patients.

Neurotransmitters are chemical messengers that nerve cells (neurons) release to communicate with each other. Serotonin plays a vital role in most systems in the body including regulation of sleep, digestion, cognition, mood and behavior. Gepirone binds to 5-HT1A receptors, protein molecules on neurons that respond to serotonin, and modulates serotonin neurotransmission, which results in reduced anxiety and mood elevation.

The enhancement of serotonin activity also works indirectly on mood by acting on other neurotransmitters, which may contribute to the anxiolytic and antidepressant effect. Stimulation of 5-HT1A receptors inhibits the release of glutamate, the major excitatory neurotransmitter, and also appears to increase the secretion of oxytocin, a neuropeptide that boosts mood, increases feelings of comfort in social situations and promotes partner bonding.

Gepirone is a partial agonist of 5-HT1A and is expected to have a better safety profile than other azapirone drugs, but may be less effective. Studies show gepirone enhances sexual desire and performance in patients with depression, and can counteract the adverse effect of sexual dysfunction caused by selective serotonin receptor inhibitor (SSRIs) class of antidepressants. Gepirone may not be effective for all individuals, but may likely be effective for a subset of patients with depression, anxiety and anxious depression.

• Gepirone may be effective only for patients with anxiety and depression and not for standalone major depressive disorder.
• Gepirone may not be as efficacious as buspirone, another azapirone, however, it has a better safety profile.
• Gepirone may worsen depression and/or suicidality as a result of 5-HT1A partial agonism and its downstream effects.
• Most studies of gepirone have been conducted for a short term, and long-term effects are unknown. It is not known if gepirone can cause withdrawal symptoms upon discontinuation. However, withdrawal is likely with discontinuation after prolonged use.

Common side effects of gepirone include:

• Nausea
• Diarrhea
• Dizziness
• Lightheadedness
• Vertigo
• Headaches
• Insomnia
• Restlessness

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Major depressive disorder

• Gepirone is yet to be approved by the FDA and information on recommended dosages is not available.
• The average dosage of gepirone used in one study was around 40 mg and it appeared to be favorably tolerated by users.

Dosage Considerations

• Effective doses of about 0.01 to 40 mg/kg body weight are contemplated. For certain central nervous system disorders, 15 to 90 mg/day, preferably 30-60 mg/day, are recommended.
• One trial showed that a low dose (10 to 45 mg/day) of gepirone can alleviate symptoms of generalized anxiety within 6 weeks of treatment onset. It is unknown as to whether larger doses (e.g., 40 to 80 mg/day) would result in a quicker onset of gepirone’s action.

Overdose

There is no information available on gepirone overdose.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

Gepirone is pending FDA approval.

Gepirone may interact with:

• CYP3A4 inducers (e.g., butalbital, carbamazepine, phenobarbital, phenytoin, St. John's wort, etc.)
• CYP3A4 inhibitors (e.g., cobicistat, indinavir, itraconazole, ketoconazole, etc.)
• monoamine oxidase inhibitors (MAOIs)
• other antidepressants

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Gepirone is an investigational drug pending FDA approval. There is no information available on the use of gepirone by pregnant or breastfeeding women.