AILSA CHANG, HOST:
Today, the Food and Drug Administration approved the first new type of drug for schizophrenia in decades. It's called KarXT, and its main advantage is that it has fewer side effects than current drugs. NPR pharmaceuticals correspondent Sydney Lupkin reports on this new development.
SYDNEY LUPKIN, BYLINE: Tiffany is a librarian in Oklahoma. She has a master's degree, a husband, four cats, a dog, a hamster and a shrimp in an aquarium. She also has schizophrenia. She asks us to use only her first name because of the stigma associated with schizophrenia. When she was first put on an antipsychotic drug, she felt like a zombie.
TIFFANY: It was my birthday, and I was opening presents. Everyone was happy, and I'm just sitting there, like, there's nothing going on. Like, I'm staring at a blank wall. And so I lied, and I told everyone I was better.
LUPKIN: So she stopped taking the drug and basically white-knuckled it for years until she experienced another psychotic episode. Then she played what she calls the meds game - trying different pills until one worked for her. But some of the side effects were brutal. Common antipsychotic drugs can cause weight gain and increase the risk of diabetes. One gave Tiffany a movement disorder.
TIFFANY: So I was pacing in my office for eight hours a day - and it is exactly 3 1/2 steps, turn, 3 1/2 steps, turn (laughter). It was a nightmare.
LUPKIN: Since the first antipsychotic drug was introduced in the 1950s, the subsequent medications to treat psychosis act on the same chemical that helps the brain communicate with the rest of the body - dopamine. Here's Dr. Ann Shinn, a psychiatrist who directs clinical research on schizophrenia and bipolar disorder at McLean Hospital near Boston.
ANN SHINN: The dopamine hypothesis proposed that schizophrenia is associated with excessive dopamine neurotransmission - so too much dopamine activity.
LUPKIN: Dopamine is the neurotransmitter usually associated with reward and learning, but it actually has a lot of functions. It also plays a role in controlling movement, for example. That's why that one drug made Tiffany pace. But for the first time, there's a new medicine for psychosis that does not act on dopamine and has had fewer side effects in clinical trials. It's called KarXT. Here's its lead inventor, Andrew Miller.
ANDREW MILLER: I became really interested in schizophrenia and, through that work, became really interested in the idea of targeting muscarinic receptors because here was serendipitous clinical finding that suggested potential efficacy, which is really hard to come by in psychiatry.
LUPKIN: He's talking about a 1997 study in Alzheimer's patients of a drug that was shelved even though it reduced psychosis. The muscarinic receptors got their name because they respond to muscarine, a chemical in some mushrooms. The problem for developing a drug to activate them in the brain is that they can trigger receptors in the gastrointestinal tract. Patients couldn't tolerate it.
So Miller and his team decided to add a second medicine, one already used for overactive bladder, to shut down the gastrointestinal receptors. The trick? That medication can't cross into the brain from the blood. That difference means it shuts down the muscarinic receptors in the body but doesn't stop the first drug from doing its job in the brain. Here's Shinn again.
SHINN = PSYCHIATRIST/DIRECTOR OF CLINICAL RESEARCH, MCLEAN HOSPITAL: Basically, Karuna kind of did this brilliant thing of putting it all together in a combination drug.
LUPKIN: She's talking about Miller's company, Karuna Therapeutics, which was acquired by pharmaceutical heavyweight Bristol Myers Squibb for $14 billion earlier this year. It's unclear how easy it will be for patients to get insurance coverage for KarXT. While the new medicine isn't for everyone, it could help patients who've had trouble with existing treatments. As for Tiffany, she's interested.
TIFFANY: Every time I have an episode, you know, I lose bits of myself and bits of functionality. And that's not fair to my husband, and I hate it. So if I could have something that would help me have a little bit more initiative, that would be wonderful.
LUPKIN: Sydney Lupkin, NPR News. Transcript provided by NPR, Copyright NPR.
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