7 Things to Know When Comparing Exxua vs. SSRIs for Depression

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Exxua (gepirone) is the newest antidepressant. In September 2023, it was FDA approved for the treatment of major depressive disorder (depression) in adults. Exxua activates certain serotonin receptors (binding sites). But it's not a selective serotonin reuptake inhibitor (SSRI).

SSRIs are the most commonly prescribed type of antidepressants. So it's common for people to compare them with other types of antidepressants. Exxua and SSRIs have a number of similarities. But they have several notable differences, from how they work to what side effects they may cause. Below, we'll cover seven things to keep in mind when comparing Exxua and SSRIs.

1. Exxua works differently from SSRIs

Exxua isn't an SSRI. It's a partial 5HT1A receptor agonist. It's actually more closely related to the antianxiety medication buspirone than SSRIs.

Exxua works by partially activating (turning on) certain serotonin receptors (binding sites). These are known as 5HT1A receptors. When the chemical messenger serotonin binds to these receptors, it helps regulate mood. Exxua targets the same receptors, acting similarly to how serotonin would. Exxua doesn't raise serotonin levels.

On the other hand, SSRIs help increase levels of serotonin in the brain. They do this by preventing your nerves from reabsorbing serotonin. By blocking reabsorption, levels of serotonin rise. This helps relieve depression symptoms.

2. SSRIs have more FDA-approved uses than Exxua

SSRIs have been available for decades. They have been researched and received FDA approvals for multiple mental health conditions. Some of them are approved to treat both adults and children.

Some FDA-approved SSRI uses include:

• Major depressive disorder

• Generalized anxiety disorder

• Obsessive-compulsive disorder (OCD)

• Panic disorder

• Post-traumatic stress disorder (PTSD)

• Social anxiety disorder

Currently, Exxua is approved only for major depressive disorder in adults. But Exxua's manufacturer is studying it for generalized anxiety disorder and hypoactive sexual desire disorder. So Exxua could be approved for other conditions in the future.

3. Exxua tablets can't be split, but many SSRIs can

You should swallow Exxua tablets whole. Don't split, crush, or chew them. If you have trouble swallowing pills, tell your prescriber. They may recommend an alternative.

Exxua is an extended-release (ER) tablet. Each tablet has a special coating that allows the medication to be released slowly over several hours. Cutting or crushing Exxua could cause the medication release too quickly, raising the risk of side effects.

Many SSRI tablets, including sertraline (Zoloft) and citalopram (Celexa), can be split in half or have oral liquid versions available. Ask your pharmacist about cutting pills if your SSRI is an ER pill or comes as a capsule. These types of pills often can't be cut, crushed, or opened.

4. Both Exxua and SSRIs can take several weeks to have full effects

Neither Exxua nor SSRIs start working immediately. They take 4 to 8 weeks to be fully effective.

But you may notice some symptom improvement sooner. SSRIs may start working in about 2 weeks. And people taking Exxua typically notice some improvement in 2 to 3 weeks.

Good to know: There are faster-working antidepressants available. One your prescriber may consider is Auvelity (dextromethorphan / bupropion). Auvelity starts working within 1 week of starting it.

5. Exxua doesn't seem to cause weight gain or sexual problems

Weight gain and sexual side effects are common concerns when it comes to taking antidepressants. These side effects are often reported by people taking SSRIs, with some SSRIs more likely to cause them than others. But with Exxua, there may be a lower risk.

One study found that people taking Exxua for 8 weeks had no significant changes in body weight. Many participants also reported improvements in sexual functioning after starting Exxua. Keep in mind, long-term studies of these side effects are limited. And often, people don't experience these side effects, especially weight gain, until they've been taking an antidepressant for a few months.

Exxua and SSRIs share a number of other common side effects. These include:

• Nausea

• Headache

• Diarrhea

• Sleepiness

• Insomnia

• Nervousness or agitation

All antidepressants also have a boxed warning (the FDA's strictest warning for medications) for suicidal thoughts and behaviors. This risk is greater with people under age 25. It's also most likely to happen during the first few months after starting an antidepressant. But keep in mind that Exxua isn't FDA approved for use in children.

6. Exxua and SSRIs have different serious side effects

Exxua can cause abnormal heart rhythms (arrhythmias). This is because it can lengthen the QT interval (the time between heartbeats). In severe cases, life-threatening arrhythmias can happen. To help prevent complications, your prescriber may check your heart rhythm before you start and while you're taking Exxua.

Some SSRIs, such as citalopram, also have a warning about possible arrhythmias. But not all SSRIs have this risk. So if you have a history of arrhythmias or you take other medications that lengthen the QT interval, your prescriber may prefer that you avoid Exxua or SSRIs that have this risk.

SSRIs can raise your risk for bleeding. This typically isn't an issue for many people. But it can be if you take blood thinners or other medications that raise the risk of bleeding. Combining these medications with SSRIs can raise the risk of serious bleeding. Exxua doesn't have this risk. So it could be a safer option if you already have a higher risk for bleeding.

This isn't a comprehensive list of all risks for either Exxua or SSRIs. It's a good idea to discuss potentially serious side effects with your healthcare team when you start taking an antidepressant.

7. Exxua and SSRIs share several interactions

Exxua and SSRIs have many differences, but they share some of the same drug interactions.

Exxua and SSRIs shouldn't be combined with medications that raise serotonin levels. Doing so raises your risk of a potentially life-threatening complication called serotonin syndrome. Medications that raise serotonin levels include:

• Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta)

• Tricyclic antidepressants, such as amitriptyline

• Monoamine oxidase inhibitors (MAOIs), such as selegiline (Emsam, Zelapar)

• Atypical antidepressants, such as trazodone

• Some opioid pain medications, such as tramadol (ConZip)

• Triptan medications for migraines, such as sumatriptan (Imitrex)

• Dextromethorphan (Delsym)

• Certain nausea medications, such as ondansetron (Zofran)

• St. John's wort (an over-the-counter dietary supplement)

As mentioned above, Exxua and some SSRIs can lengthen the QT interval. Many other medications, including antipsychotic medications and common antibiotics, also have this side effect. Combining medications that lengthen the QT interval raises the risk of developing abnormal heart rhythms.

This isn't a full list of all possible interactions for Exxua or SSRIs. Share a list of the medications you take with your prescriber and pharmacist so they can check for interactions. Include any over-the-counter medications, vitamins, and supplements on this list.

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