A new drug for schizophrenia promises fewer side effects

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

The twice-daily pill to be marketed by Bristol Myers Squibb will be called Cobenfy, although it was called KarXT during development. Its main advantage is that it appears to have fewer side effects than current medications.

This difference has caught 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.

The first time she was given an antipsychotic, she says, it made her feel like a zombie. When she watched a video from her birthday party that year, she didn't recognize herself.

“I opened presents – everyone was happy. And I just sit there like nothing's going on. I’m staring at a blank wall,” she says. “And so I lied and told everyone I was feeling better.”

So she stopped taking the medication and stayed off it for years until she experienced another psychotic episode.

Then she played what she calls the “medication game,” trying different pills until one worked for her. But some of the side effects were brutal. Common antipsychotics can cause weight gain and increase the risk of diabetes.

One gave Tiffany a movement disorder.

“So I've been walking up and down my office for eight hours a day, and it's exactly 3 1/2 steps, turn around, 3 1/2 steps, turn around,” she says. “It was a nightmare.”

Decades of dopamine-focused drugs

Since the first antipsychotic was introduced in the 1950s, subsequent medications used to treat psychosis target 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 – that is, too much dopamine activity,” he says Dr. Ann Shinna psychiatrist who leads 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 many functions. It also plays a role in movement control, for example – that's why this one drug made Tiffany go faster.

The new drug targets different brain receptors

Cobenfy is the first new psychosis drug that does not affect dopamine.

“I was really interested in schizophrenia and through this work I became really interested in the idea of ​​targeting muscarinic receptors because it was an incidental clinical finding that suggested potential efficacy that is really hard to achieve in psychiatry “, says the main inventor of the drug. Andrew Miller.

He talks about a 1997 study in Alzheimer's patients about a drug that was shelved even though it reduced psychosis.

Muscarinic receptors get their name because they respond to muscarin, a chemical found in some mushrooms. The problem with developing a drug to activate these substances in the brain is that they can trigger receptors in the gastrointestinal tract. The patients couldn't tolerate it.

So Miller and his team decided to add a second drug — one already used for overactive bladder — to turn off the gastrointestinal receptors. The trick: The drug cannot reach the brain via the blood.

This means that it switches off the muscarinic receptors in the body, but does not prevent the first drug from exerting its effects in the brain.

“Basically, Karuna has managed to combine everything into one combination product,” says Shinn.

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

How much will it cost?

According to Bristol Myers Squibb, the drug will be available starting in October for $1,850 per month, which is comparable to other schizophrenia treatments. It's unclear how easy it will be for patients to get insurance coverage for Cobenfy.

“If it's like many other new medications, insurance will generally require people to try at least two generics first… before paying for them,” says Dr. Jacob Ballon, associate professor of psychiatry at Stanford University.

Nevertheless, he says, he has many patients – and their parents – who are enthusiastic about a possible new treatment option. Ballon is working on an ongoing study into how Cobenfy fits with existing medications and whether they can be used together.

Although the new drug isn't for everyone, it could help patients who have had problems with existing treatments.

The FDA based its approval on 5-week double-blind, placebo-controlled studies. This means that some patients received Cobenfy and others received a placebo, but neither the patients nor the doctors knew which was which until the study was completed. The short duration of the study has led some experts to point out that questions remain about the drug's long-term safety and effectiveness.

Common side effects of Cobenfy include nausea, constipation, and fast heartbeat.

Tiffany is interested in trying the drug later. Unlike previous medications that only addressed the so-called positive symptoms of schizophrenia, such as hallucinations and delusions, Cobenfy was proven to relieve the “negative” symptoms such as apathy and lack of motivation.

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

She also has some advice for people with schizophrenia who are still looking 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 big difference, day and night.”

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