Recent Update- Zuranolone And Gepirone

Zuranolone

The GABA A receptor is impacted by the active steroids. Allopregnanolone, pregnanolone, tetrahydeoxycorticosterone, dehydroepiandrosterone (DHES-S), and DHEA are a few neuroactive steroids.

Mechanism Of Action

Zuranolone is an oral neuroactive steroid that is derived from allopregnanolone, a naturally occurring active steroid.  Zuranolone influences both synaptic and extrasynaptic GABA. It functions as a positive allosteric modulator of the GABA A receptor. via attaching to the GABA A receptor's non-benzodiazepine site and causing a conduction.

The FDA authorized Zuranolone on August 4, 2019, for the treatment of postpartum depression in adults.  Postpartum depression was approved for the use of brexanolone IV. The first oral medication to be approved is Zuranolone.

According to phase 3 clinical trials, such as the study by Robin and Skylark, postpartum depression improved on the third day of Zuranolone.

Side-effects 

Drowsiness is the most typical side effect of Zuranolone. Dizziness, diarrhea, exhaustion, urinary tract infection, and nasopharyngitis are among the other adverse symptoms. It can also result in fetal harm. Suicidal thoughts and actions can also be brought on by it. Effective contraception should be used by women both during and for one week following the last dosage of Zuranolone.

During the course of a 14-day treatment course, patients are advised not to drive or perform other potentially hazardous activities, such as operating machinery, until at least 12 months after administration. Additionally, patients should be informed that they may not be able to assess the degree of driving impairment caused by Zuranolone or their own driving competence.

Dosage

Zuranolone can be used either on its own or in addition to oral antidepressant medication. The safety and efficacy of use beyond 14 days in a single treatment session have not been established. The dosage of 50 mg should be taken once daily for 14 days in the evening with a fatty meal.

In the event that a CNS depressing effect manifests, the daily dosage may be lowered to 40 mg once day. 30 mg once weekly for 14 days is the recommended dosage for moderate to severe renal impairment and severe hepatic impairment.

Zuranolone comes in capsule form and is available in dose strengths of 20, 20, and 50 mg.

Also Read: How Do Different Patterns Of Injury Influence Psychiatric Disorders?

Metabolism

The dose adjustments are required for concurrent usage with CYP3A4 inducers or inhibitors because it is metabolized by CYP 3A4. In adults, zuranolone has a terminal half-life of 19.7–24.6 hours.

Drug Interactions

Zuranolone may worsen CNS depressive symptoms or psychomotor impairment when used in combination with other CNS depressants. When taking these medications simultaneously, the drug should be avoided or the dosage should be lowered.

Severe CYP34A inhibitors may raise blood levels of zuranolone and cause negative side effects. As a result, for 14 days, the dosage should be lowered to 30 mg/dl.In addition, CYP3A4 inducers result in a reduction in efficacy.

Gepirone

Gepirone is regarded as an antagonist at the 5HT2A serotonin receptor and an agonist at the 5HT1A receptor.It is a member of the Buspirone family. The medication busperidone is authorized to treat generalized anxiety disorder.

Mechanism Of Action

Gepirone binds to the somatodendritic site's presynaptic 5HT1A receptors, desensitizing or downregulating the receptors in the process.It then stops preventing serotonin neurons' impulse flow, which causes 5HT to be released from the axon terminal.

In 2023, however, gepirone received FDA approval for the treatment of major depressive disorder in adults after being refused in 2004, 2007, and 2015.

Side-effects

Symptoms such as nausea, dyspepsia, dizziness, and sleeplessness are frequently experienced after taking gepirone.

In bipolar disorder patients, serotonin syndrome and manic episodes are fewer frequent side effects of gepirone.

Contraindications

If a person has a hypersensitivity to gepirone or any of its ingredients, they should not take gepirone. In addition, it should not be administered if congenital long QT syndrome or a prolonged QTc interval (more than 450 seconds) exist.

Any electrolyte imbalances should be rectified before starting gepirone therapy, and levels should be monitored during the course of treatment due to the possibility of QT prolongation.

ECGs should be performed before starting medication, throughout dose titration, and on occasion while receiving treatment.

Approved Labelling

Weight gain and sexual dysfunction are not listed as side effects of Gepirone in the approved labels. Despite not being authorized for use in that population, the boxed warning increases the risk of suicidal thoughts and actions among young adults and children.

Precautions

Gepirone side effects include serotonin syndrome and the induction of mania or hypomania.

Dosage

The following strengths of extended release tablets are available: 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg. Depending on clinical response and tolerability, the dose can be increased to 36.3 mg once daily on day 4, 54.5 mg once daily after day 7, and 72.6 mg once daily after an extra week. The suggested starting dose is 18.2 mg orally once daily with food.

For elderly patients with moderate hepatic impairment and renal impairment with a Crcl of less than 50 ml/min, the initial dose is 18.2 mg once day. After seven days, a maximum dose of 36.3 mg once daily is advised.

It is not recommended for patients taking powerful CYP3A4 inhibitors, and the dose of gepirone should be lowered by 50% when used concurrently with them.

Hope you found this blog helpful for your Psychiatry residency Neurology and General Medicine preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.