A new kind of drug for schizophrenia promises fewer side effects

Caption

The Food and Drug Administration approved Cobenfy, a twice-a-day medication that is a new kind of treatment for schizophrenia in adults. / Bristol Myers Squibb

For the first time in decades, the Food and Drug Administration has approved a new type of drug for schizophrenia.

The twice-a-day pill to be marketed by Bristol Myers Squibb will be called Cobenfy, though it had been referred to as KarXT during development. Its main advantage is that it appears to have fewer side effects than current medicines.

That difference has captured the attention of patients like Tiffany, a librarian in Oklahoma. She asked us to use only her first name because of the stigma associated with schizophrenia.

When she was first put on an antipsychotic drug, she says it made her feel like a zombie. Watching a video of her birthday party that year, she didn’t recognize herself.

“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,” she says. “And so I lied and I told everyone I was better.”

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 for diabetes.

One gave Tiffany a movement disorder.

“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,” she says. “It was a nightmare.”

Decades of dopamine-focused drugs

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.

“The dopamine hypothesis proposed that schizophrenia is associated with excessive dopamine neurotransmission — so too much dopamine activity,” says Dr. Ann Shinn, a psychiatrist who directs clinical research on schizophrenia and bipolar disorder at McLean Hospital near Boston.

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.

The new drug targets different brain receptors

Cobenfy is the first new medicine for psychosis that does not act on dopamine.

“I became really interested in schizophrenia and through that work became really interested in the idea of targeting muscarinic receptors because here was a serendipitous clinical finding that suggested potential efficacy, which is really hard to come by in psychiatry,” says the drug’s lead inventor, Andrew Miller.

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 means it shuts down the muscarinic receptors in the body but doesn’t stop the first drug from doing its job in the brain.

“Basically Karuna kind of did this brilliant thing of putting it all together in a combination drug,” Shinn says.

She’s talking about Miller’s company, Karuna Therapeutics, which was acquired by pharmaceutical heavyweight Bristol Myers Squibb for $14 billion dollars earlier this year.

How much it will cost?

Bristol Myers Squibb says the drug will be available starting in October at $1,850 a month, which is in line with other schizophrenia treatments. It’s unclear how easy it will be for patients to get insurance coverage for Cobenfy.

“If it's like a lot of the other new medications, insurance is generally going to mandate that people try at least two generic medicines first … before they will pay for it,” says Dr. Jacob Ballon, an associate professor of psychiatry at Stanford University.

Still, he has a lot of patients — and their parents — who are excited about a potential new treatment option, he says. Ballon is working on an ongoing study of how Cobenfy fits in with existing drugs and whether they can be used together.

While the new medicine isn’t for everyone, it could help patients who’ve had trouble with existing treatments.

The FDA based its approval on 5-week double-blind, placebo-controlled studies. That means some patients received Cobenfy and others got a placebo, but neither the patients nor the clinicians knew which was which until the study was over. The short study length has prompted some experts to point out that questions remain about the drug’s long-term safety and efficacy.

Common side effects with Cobenfy include nausea, constipation and rapid heartbeat.

As for Tiffany, she’s interested in trying the drug down the road. Unlike previous drugs which only tackled the so-called positive symptoms of schizophrenia, like hallucinations and delusions, Cobenfy has been shown to decrease the “negative” symptoms, such as apathy and lack of motivation.

“Every time I have an episode, I lose bits of myself and bits of functionality … and that's not fair to my husband, and I hate it,” she says. “So if I could have something that would help me have a little bit more initiative, that would be wonderful.”

She also has some advice for people with schizophrenia who are still searching for the right treatment.

“Just keep trying,” she says. “It's really hard to go on and off medications, but when you find the right one, it makes a huge difference — night and day.”