FDA approves Simtriyo (centanafadine), a ‘first of its kind’ ADHD medication

The Food and Drug Administration (FDA) just approved Simtriyo (centanafadine), a new norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI) and central nervous system stimulant. The medication treats ADHD in adults, teens, and children ages 6 and up weighing at least 44 pounds. 

Most stimulant and non-stimulant ADHD medications raise the levels of two different brain chemicals related to ADHD (dopamine and norepinephrine). Simtriyo is the first to boost dopamine, norepinephrine, and a third neurochemical, serotonin, which affects mood and executive functioning. This gives people with ADHD a new option, not just for improving core ADHD symptoms, but for mood and executive functioning too. 

And Simtriyo, an extended-release pill meant to be taken once a day, works without causing some of the side effects that come with other ADHD stimulants and non-stimulants.

“There are a lot of people, especially adolescents, who feel like the stimulants really help, but don’t like the way they feel on them,” says Jodi Gold, MD, an adult and pediatric psychiatrist. “The idea that we could find a good medication for ADHD that doesn’t have such a big impact on sleep, insomnia, and appetite is huge.”

Here’s what to know about this new ADHD treatment option. 

Most ADHD medications — including the stimulants Adderall (mixed amphetamine and dextroamphetamine salts), Ritalin (methylphenidate), and Vyvanse (lisdexamfetamine), and the non-stimulants Strattera (atomoxetine) and Qelbree (viloxazine) — work by managing neurotransmitters, chemicals that help send messages across the brain. This is because ADHD brains have trouble getting enough neurotransmitters like dopamine, which controls how your brain processes rewards and pleasure, and norepinephrine, which helps control attention.

“Twenty years ago, when we thought about ADHD, we thought about dopamine and norepinephrine. Easy peasy, when you block [reuptake of] dopamine and norepinephrine, people concentrate better, they’re less hyperactive, less busy, less impulsive, and everything is good,” explains Ann Childress, MD, a psychiatrist and president of the Center for Psychiatry and Behavioral Medicine, who helped conduct many of the clinical trials on Simtriyo. “But the brain is a lot more complicated than that.”

Scientists have since learned that ADHD is about more than just attention and hyperactivity. Mood and executive functioning also play a big role, which is why researchers and drugmakers have been trying to find ways to target a third neurotransmitter — serotonin. 

“Serotonin regulates a whole lot of things. It regulates mood, it regulates sleep, and it regulates emotional balance,” says Childress.

Simtriyo, which is manufactured by the pharmaceutical company Otsuka, boosts serotonin in addition to dopamine and norepinephrine. In one analysis, Otsuka looked at data from 744 of the adultsopens in a new tab in the drug’s clinical trials. Many participants said they had better executive functioning after taking Simtriyo for six weeks. 

And many reported improvements in time management, planning and prioritization, starting and finishing tasks, and working memory. There was a mood component as well. The same adults were more likely to say they had reductions in emotional overactivity, mood shifts, and anger outbursts.

Of course, Simtriyo is not the first medication to target serotonin. Selective serotonin reuptake inhibitor (SSRI) drugs — like Zoloft, Prozac, and Lexapro — do the same thing. However, these drugs are most often used to treat anxiety and depression. 

It’s important to note that Simtriyo is not an anxiety or depression medication. The drug has only been tested for how it affects ADHD symptoms. But Otsuka shared dataopens in a new tab showing that Simtriyo works well in adults who have both ADHD and social anxiety or generalized anxiety disorder. That’s likely because of Simtriyo’s effect on serotonin, Childress says. 

Otsuka tested Simtriyo in four phase 3 clinical trials.opens in a new tab Those studies included adults ages 18 to 55,opens in a new tab adolescents ages 13 to 17,opens in a new tab and kids ages 6 to 12.opens in a new tab The clinical trials found the drug to be safe for use by kids, teens, and adults. 

Side effects were mostly mild in the participants who experienced them. Some of the most common side effects included: 

• Decreased appetite

• Rash

• Vomiting 

• Nausea

• Headache

In clinical trials, about a third of adults and children and half of adolescents experienced side effects after taking Simtriyo. That’s compared to about a quarter of the placebo groups in each trial. 

In the clinical trial of 6- to 12-year-olds, common side effects reported were:

• Lower appetite: 5%

• Rash: 3% 

• Vomiting: 3% 

In the clinical trial of adults, common side effects reported were: 

• Decreased appetite: 6.5%

• Headaches: 4.5%

• Dry mouth: 5.5% 

• Nausea: 5.5%

According to Childress, Otsuka is currently working on long-term studies of Simtriyo, which may tell us whether the drug affects appetite or children’s growth after taking the drug for months or years. 

We don’t know exactly how Simtriyo compares to other ADHD stimulants and non-stimulants just yet. To learn that, scientists will have to do what’s called a “head-to-head study,” where they give participants different medications under the same conditions. 

But researchers have already done some studies that compare findings from different clinical trials to make indirect comparisons between Simtriyo and other drugs. One study comparing Simtriyo with other drugsopens in a new tab found that Simtriyo seems to work about the same as the stimulant Ritalin, and less effectively than the stimulant Vyvanse. But it came with fewer safety issues than both those drugs. Simtriyo seems less likely to cause decreased appetite, headache, and insomnia compared to Ritalin. 

Gold said she hopes the drug can work as well as other ADHD medications for most patients without the same side effects. Especially for people who tend to have difficulties sleeping, high blood pressure, or anxiety symptoms that sometimes accompany stimulant medication use. The clinical trials also showed low abuse potential,opens in a new tab meaning people didn’t use Simtriyo for reasons they shouldn’t. 

“There’s the potential for this to be like a game changer for people that really don’t tolerate stimulants, which is a lot of people,” Gold says. 

Simtriyo may be easier to tolerateopens in a new tab than non-stimulant drugs. People who take Strattera (atomoxetine) often lose their appetite or experience insomnia.opens in a new tab Those side effects weren’t very common in the Simtriyo clinical trials. 

Simtriyo could take longer to kick in, though, says Childress. In clinical trials, people experienced improvements in their ADHD symptoms within a weekopens in a new tab of taking the drug, instead of right away, like with some ADHD stimulants. However, Simtriyo works fasteropens in a new tab than some non-stimulant medications, like Strattera, which can take several weeks to kick in. 

Psychologist Dr. Ari Tuckman answers questions about ADHD treatments.

Simtriyo will be available later this year after scheduling by the U.S. Drug Enforcement Administration (DEA). It’s a new drug, so it may not be covered by insurance right away. If you’re interested in seeing if it’s an option for you, the first step is to talk to your health care provider. 

When prescribing a new medication, your health care provider will take into account lots of factors, Gold says. That includes whether you have other health conditions that could be affected by the medication, a family history of addiction, or a personal history of body image or weight problems.

“We often see new forms of Ritalin and Adderall coming out, and families do research on those on their own,” Gold says. “But with this medicine, since it’s a new mechanism, it’s really important to get the information and the safety data from your doctor.”

For adults, the recommended starting dose of Simtriyo is 210 mg orally once daily. For teens 13 to 17 years, the recommended dose is 280 mg orally once daily. For children ages 6 to 12, your doctor will set the dose based on your child’s weight.

Childress also said that it’s good to be cautious anytime you’re taking multiple drugs that affect serotonin levels. Be sure to tell your doctor about all the medications you take, including prescription medication, over-the-counter medicines, supplements, and vitamins. And if you’re taking an antidepressant or anti-anxiety medication, Childress recommends talking with your doctor about the risks and benefits of taking Simtriyo.

Understood is not affiliated with any pharmaceutical company.

Thumbnail image credit: Jacob Wackerhausen via Getty Images.