Vinod H. Srihari, MD, is a professor of psychiatry at the Yale School of Medicine in New Haven, Connecticut. The information here represents his research and knowledge as a medical professional. Srihari was not involved in the clinical trials for xanomeline and trospium chloride (Cobenfy).
Psychiatrists spend a lot of time with patients who have schizophrenia. Schizophrenia is a mental health condition that affects how a person thinks, feels, and behaves. Although it occurs in less than 1% of all Americans, its effects can be devastating. People with schizophrenia often have reality distortion. They may have hallucinations, such as hearing voices that aren’t there. They may also develop delusions, like someone wants to harm them.
Although there has been a lot of progress to understand, diagnose, and treat schizophrenia, we still have a lot to learn. We do know that early, intensive treatment often leads to better outcomes. The goal is to make sure patients with schizophrenia manage their symptoms and lead productive lives.
Though there are good treatments for schizophrenia, they often come with side effects like weight gain, drowsiness, or involuntary body movements. Now, there’s a new, promising treatment available called Cobenfy. It’s a combination of two drugs: xanomeline and trospium chloride. It works in a very different way from other drugs available for schizophrenia, which means it doesn’t have the same side effects.
There haven’t been many studies on Cobenfy. We’ll want to see more research on it before we start to recommend it to patients. But it’s one of the biggest breakthroughs in schizophrenia treatment that we’ve seen in decades.
Who is Cobenfy for?
Cobenfy was FDA approved in September 2024 to treat adults with schizophrenia. I personally haven’t prescribed it to any of my patients yet. I want to see some longer-term data on its safety and efficacy. But it could turn out to be a very important first-line treatment for people diagnosed with schizophrenia. It’s also being studied now as an adjunctive treatment, which means it would be used along with other treatments for schizophrenia. We will, hopefully, see those study results sometime in 2025 or 2026.
How does Cobenfy work?
Cobenfy works quite differently from other drugs for schizophrenia. Older medications block dopamine, a brain hormone associated with schizophrenia. Instead, Cobenfy works more indirectly to reduce dopamine. It targets muscarinic receptors, which are brain proteins that help to regulate dopamine. It’s exciting because it may open the door to the development of other drugs to treat schizophrenia that also impact muscarinic receptors. We haven’t had a new drug like this for decades.
How effective is Cobenfy?
Researchers tested Cobenfy in two identical five-week clinical trials of 252 adults between the ages of 18 and 65. They all had a diagnosis of schizophrenia, and they’d all had a recent worsening of psychosis symptoms such as hallucinations that landed them in the hospital. The study found that Cobenfy had a “significant” impact on some of these most difficult symptoms.
The researchers used something called the Positive and Negative Syndrome Scale (PANSS) to measure the drug’s effectiveness. It’s a tool that’s often used to score the severity of a patient’s schizophrenia symptoms. People who took Cobenfy scored about 10 points higher on PANSS at the end of the trial compared to those who took a placebo.
This sounds very impressive, but there are a couple things to keep in mind. To get FDA approval, drugs like Cobenfy only need to show that they are better than a placebo, or no treatment. We don’t have any head-to-head trials of Cobenfy yet against other schizophrenia treatments. The studies also weren’t very long – just five weeks. I’d like to see longer studies, both of Cobenfy versus placebo and Cobenfy versus other schizophrenia drugs, before I start to prescribe it to my patients.
The other thing that struck me when I reviewed the data was that Cobenfy appeared to have the best results when it came to relieving the positive symptoms of schizophrenia. Positive symptoms are those that are present with a condition. For schizophrenia, that’s symptoms such as hallucinations and paranoia. These are the symptoms that are often most distressing, both for patients themselves and their loved ones and caretakers. But it doesn’t appear to have as big of an impact on negative symptoms. These include things like withdrawal from others, trouble planning and doing activities, and low energy. We’ll need more data to know for sure.
Is Cobenfy safe?
According to research so far, yes, it is. But we only have data now that’s five weeks out. To get FDA approval, a medication just needs to show that it’s safe in short-term studies and that it’s better than a placebo. We’re not going to see very rare, potentially dangerous side effects, or those that develop over time, with such a small, short-term sample.
Unlike some other antipsychotic drugs that are used to treat schizophrenia, Cobenfy doesn’t have an FDA boxed warning. It’s a very serious warning given by the FDA for drugs that have the potential to carry significant risk or side effects. It’s reassuring, but we’ll need to see if that changes once larger, longer studies are conducted.
We also don’t know how people with other conditions, such as heart or lung disease, will do on this drug. Since we don’t yet know about long-term safety or longer-term side effects, I would encourage any patient on this drug to check in at least once a week with their doctor to keep an eye out for anything unusual.
What are the common side effects of Cobenfy, and are there ways to manage them?
The most common side effects seen with Cobenfy in the clinical trials were GI ones such as constipation, diarrhea, heartburn, nausea, and vomiting. These types of side effects often get better with time as your body gets used to the medication. The drug manufacturer also recommends that you take it on an empty stomach, at least one hour before meals or two hours afterward. This may help with side effects, too.
Other, less reported side effects included headache and an increase in blood pressure. If you experience any of these, always tell your doctor. They may be able to adjust your dose or offer other suggestions to make side effects more manageable.
Reassuringly, Cobenfy doesn’t seem to have the metabolic side effects of other schizophrenia treatments, like weight gain or fatigue. There also haven’t been reports of tardive dyskinesia, or involuntary body movements. This can happen when you block dopamine receptors in the body. We tend to see these more with other antipsychotic medications such as Risperdal (risperidone) or Zyprexa (olanzapine).
How is Cobenfy taken? Is follow-up testing or monitoring needed? Do you take it for life?
Cobenfy is taken as a pill by mouth twice a day: once when you wake up, and once before you go to bed at night. Take it on an empty stomach, and don’t open the capsules. It’s available in three doses: 50 mg/20 mg, 100 mg/20 mg, or 125 mg/30 mg. Your doctor will decide which dose is right for you.
Since Cobenfy is such a new drug, it’s hard to know exactly what follow-up testing or monitoring would look like. But with any antipsychotic medication, we tend to check blood glucose, cholesterol, and blood pressure, as well as liver and kidney function, four to eight weeks after the start of the drug. If that’s normal, we will move to 12 weeks, and then six months, and then annually. If it’s not, we would want to check them more frequently.
Who shouldn’t take Cobenfy?
Right now, I’d urge caution for everyone until we get more long-term data on the drug. But people with liver or kidney problems should probably avoid it, as should folks who have trouble with urination due to underlying conditions like an enlarged prostate. Cobenfy can make it harder for you to empty your bladder. It’s also not recommended for people with certain GI diseases, such as the inflammatory bowel disease called ulcerative colitis, or for people who already have glaucoma. Cobenfy may make both of these conditions worse.
When will Cobenfy be available?
It's available now. The catch is that it is very expensive. The list price, without insurance, is $1,850. It’s also not clear yet how easy it will be to get insurance coverage. Since it’s so new, both Medicare and Medicaid and commercial health insurance companies may want to see stronger evidence that it’s more effective than other, less expensive schizophrenia treatments out there.
How can I learn more about whether Cobenfy is a good treatment for me?
It’s best to have a heart-to-heart conversation with your medical provider. You’ll want to talk about the potential benefits versus the risks and side effects. My advice is to wait for more studies on Cobenfy to come out. This will help give us a better idea of who is the right candidate for the drug. But if you’re unhappy with your current schizophrenia treatment – for example, you’re on a medication that has caused significant weight gain that hasn’t responded to lifestyle measures like changes in diet and exercise – then you may want to consider a switch. You’ll need to be closely followed and monitored, though.
The good news is it’s another option for people with schizophrenia who are unhappy with their current treatment. About a third of patients end up switching their medication within the first year of treatment. It’s good for them to know there’s another choice that may not have the same side effects.
It’s also important to remember that drug therapy is just one part of schizophrenia treatment. Psychotherapy and social support are also crucial to help a patient succeed. People with schizophrenia also often face obstacles to treatment such as diagnosis delays and trouble accessing medication. We need to focus on ways to deliver better care at all stages of the disease. This way, patients can live the most fulfilling and productive lives possible.