Alternative to Meds Editorial Team
Medically Reviewed by Dr John Motl MD
Don’t stop or switch an antipsychotic on your own. Any change should be planned with your prescriber, because stopping suddenly can lead to withdrawal and relapse.
- Medication
- Cobenfy (xanomeline and trospium chloride), an oral capsule
- Approved for
- Schizophrenia in adults (FDA approval September 26, 2024)
- What’s new
- The first schizophrenia medicine that targets muscarinic (acetylcholine) receptors instead of blocking dopamine
- Common side effects
- Nausea, indigestion, constipation, vomiting, high blood pressure, stomach pain, diarrhea, fast heart rate, dizziness, acid reflux
- Serious risks
- Urinary retention, liver problems, slowed gut movement, facial swelling (angioedema), narrow-angle glaucoma
- Boxed warning
- None on the current label
- Still unknown
- How it compares head-to-head with older antipsychotics, and long-term results beyond about a year
- At ATMC
- We don’t prescribe Cobenfy. We help people review and safely taper psychiatric medications.
Table of contents (11)
What is Cobenfy?
Cobenfy (xanomeline and trospium chloride) is a prescription capsule for schizophrenia in adults. The U.S. Food and Drug Administration (FDA) approved it on September 26, 2024, calling it the first antipsychotic for schizophrenia that targets cholinergic receptors rather than dopamine receptors.1
For decades, schizophrenia medicines have worked mainly by blocking dopamine. Cobenfy takes a different route, so its side effects are different too. It tends to cause stomach upset rather than the weight gain, sleepiness, and movement problems many people know from older antipsychotics.2,3
It is a meaningful new option, but it is not right for everyone, and long-term data are still limited. This guide explains how it works, what the label says, and what to talk over with your prescriber.
Want medical support while you taper? Learn how our residential medication tapering program in Sedona works, or call (888) 907-7075.
How Cobenfy differs from older antipsychotics
Short answer: older antipsychotics block dopamine receptors. Cobenfy instead switches on certain acetylcholine receptors in the brain, called M1 and M4 muscarinic receptors.2
Cobenfy combines two medicines in one capsule:
- Xanomeline is the active treatment. Its benefit in schizophrenia is thought to come from stimulating M1 and M4 receptors in the brain, though the exact mechanism is not fully understood.2
- Trospium chloride blocks muscarinic receptors mainly in the body outside the brain.2 Researchers added it to reduce side effects that xanomeline alone caused, such as nausea, vomiting, and sweating.10
| Older antipsychotics (for example, Seroquel, Zyprexa, Risperdal) | Cobenfy | |
|---|---|---|
| Main target | Block dopamine receptors | Activates M1 and M4 muscarinic receptors2 |
| Boxed warning | Yes: higher risk of stroke and death in older adults with dementia8,9 | None on the current label2 |
| Typical side effect concerns | Weight and blood sugar changes, sleepiness, movement problems such as tardive dyskinesia8 | Nausea, constipation, indigestion, vomiting, higher blood pressure and heart rate2 |
| Weight gain in trials | Common with many second-generation drugs | Similar to placebo in the 5-week trials3,4 |
| How it’s taken | Pills once or twice a day, and some come as long-acting injections | Capsule twice a day, on an empty stomach2 |
The absence of a boxed warning does not mean Cobenfy has no serious risks. It has its own warnings, covered below.2
New to antipsychotics? Learn how the different types work and why people take them.
FDA approval and what the label says
Short answer: Cobenfy is approved only for schizophrenia in adults. The approval rested on two 5-week trials, and the label lists five conditions in which it should not be used.1,2
The trials behind the approval. In EMERGENT-2 and EMERGENT-3, adults hospitalized with worsening schizophrenia took Cobenfy or placebo for 5 weeks.3,4 Symptom scores (PANSS) dropped by about 21 points on Cobenfy versus about 12 points on placebo in both trials.3,4 Rates of movement side effects, weight gain, and sleepiness were similar to placebo.3,4
Who should not take Cobenfy, according to the label:2
- People with urinary retention
- People with moderate or severe liver impairment
- People with gastric retention (the stomach doesn’t empty properly)
- Anyone who has had an allergic reaction to Cobenfy or trospium
- People with untreated narrow-angle glaucoma
The label also says Cobenfy is not recommended for people with mild liver impairment or moderate to severe kidney impairment.2 Before starting, prescribers are asked to check liver enzymes, bilirubin, and heart rate.2 The capsules are taken at least 1 hour before or 2 hours after a meal, and should not be opened.2 Your prescriber decides the dose and how it is adjusted.
Pregnancy. There is no data on Cobenfy in pregnancy. The label notes that untreated schizophrenia also carries risks, and a pregnancy registry tracks outcomes.2 If you are pregnant or planning to be, talk with your prescriber before any change.
Cobenfy side effects
Short answer: the most common side effects are stomach-related, plus higher blood pressure and heart rate. In the trials, most were mild to moderate.2,3
| Side effect | Cobenfy | Placebo |
|---|---|---|
| Nausea | 19% | 4% |
| Indigestion (dyspepsia) | 18% | 5% |
| Constipation | 17% | 7% |
| Vomiting | 15% | 1% |
| High blood pressure | 11% | 2% |
| Stomach pain | 8% | 4% |
| Diarrhea | 6% | 2% |
| Fast heart rate | 5% | 2% |
| Dizziness | 5% | 2% |
| Acid reflux | 5% | under 1% |
Pooled 5-week trial data from the Cobenfy prescribing information.2
Heart rate. In the trials, heart rate rose most around day 8, by an average of 13.5 beats per minute on Cobenfy versus 4 on placebo, and then partly settled.2
Serious side effects listed in the label warnings:2
- Urinary retention. Trouble emptying the bladder. Older adults and men with an enlarged prostate are at higher risk.
- Liver problems. Liver enzyme increases have occurred. The label says to stop Cobenfy if there are signs of significant liver injury.
- Slowed gut movement. Caution is advised with ulcerative colitis, bowel obstruction, and myasthenia gravis.
- Angioedema. Swelling of the face, lips, tongue, or throat. This is an emergency.
- Narrow-angle glaucoma. Cobenfy can widen the pupils, which may set off a sudden glaucoma attack in people with narrow eye angles.
- Confusion or drowsiness. Anticholinergic effects on thinking can occur, especially in older adults and people with kidney problems. Don’t drive until you know how Cobenfy affects you.
Weight and metabolism. In the 52-week extension study, Cobenfy was not linked to meaningful weight gain, prolactin increases, movement problems, or metabolic changes.5 In a separate year-long study, about 6% of participants reported weight loss.6
What we still don’t know
Short answer: Cobenfy is new, and the evidence is still building. Here is what is uncertain:
- Long-term results. The longest studies run about one year, and they were open-label (everyone knew they were taking Cobenfy). About half of participants finished the 52-week EMERGENT-5 study, and about 1 in 5 finished EMERGENT-4.5,6
- Head-to-head comparisons. The approval trials compared Cobenfy with placebo, not with other antipsychotics.3,4
- Adding it to another antipsychotic. In the ARISE trial, adding Cobenfy to an existing antipsychotic did not significantly improve symptoms compared with placebo. Bristol Myers Squibb announced the result on April 22, 2025.7
- Other conditions. Cobenfy is approved only for schizophrenia in adults. It is being studied for psychosis linked to Alzheimer’s disease, but it is not approved for that use.2,13
- Older adults. The controlled trials did not include people over 65.2
Most of the published Cobenfy research was funded and run by the company that developed it.5,6 That is common for new drugs, but independent studies will add to the picture over time.
Who might Cobenfy suit?
Short answer: that is a decision for you and your prescriber. Based on the label and trial data, these are the kinds of factors they may weigh.
| May be worth discussing if you… | May not be a good fit if you… |
|---|---|
| Have had weight gain or blood sugar changes on a dopamine-blocking antipsychotic3,5 | Have urinary retention or an enlarged prostate with trouble urinating2 |
| Have had movement side effects or high prolactin5 | Have liver disease or moderate to severe kidney disease2 |
| Feel too sleepy on your current medication3 | Have untreated narrow-angle glaucoma, gastric retention, or certain bowel conditions2 |
| Can take a capsule twice a day away from meals2 | Need a long-acting injection, or find a twice-daily empty-stomach routine hard to keep2 |
Many people do well on the medication they already take. A new option is worth knowing about, but it is not a reason to change something that is working without a careful conversation.
Thinking about switching? Talk to your prescriber first
Short answer: please don’t stop your current antipsychotic to try Cobenfy, and don’t start Cobenfy on top of it, without your prescriber’s plan. Stopping an antipsychotic suddenly can cause withdrawal symptoms, and stopping antipsychotic treatment raises the risk of relapse.9,14
In the EMERGENT-5 study, people whose schizophrenia was stable were switched from their previous antipsychotic to Cobenfy under study supervision.6 That shows switching can be done with care. It does not tell you how your own switch should go. The timing depends on which medicine you take now, your dose, how long you have taken it, and your history.
Questions to bring to your appointment:
- What do you hope Cobenfy would do better for me than my current medication?
- Do I have any condition that rules it out, such as bladder, liver, kidney, or eye problems?
- How would we move from my current medication, and how will you watch for relapse?
- Which side effects should I report right away?
- Will my insurance cover it?
If you want to reduce or come off antipsychotics rather than switch, that also needs a slow, supervised plan. Read about antipsychotic tapering and antipsychotic withdrawal, or see our guides to Seroquel withdrawal and tardive dyskinesia.
Want a second look at your antipsychotic? Talk to our team about a supervised medication review and taper in a residential setting.
Call (888) 907-7075Free, confidential consultation
Helping a loved one
- Notice changes early. Gradual changes in thinking, mood, and social life often come before an episode of psychosis.11 Let the care team know what you see.
- Watch for Cobenfy-specific problems. Trouble urinating, swelling of the face, lips, or throat, or new confusion need prompt medical attention.2
- Help with the routine. Twice-daily doses taken away from meals can be hard to remember.2 A simple schedule can help.
- Go to appointments if they want you there. A second set of ears helps with questions about switching or side effects.
- Take talk of suicide seriously. Call or text 988 any time, or 911 in an emergency.12
Where ATMC fits
Alternative to Meds Center is a residential treatment center in Sedona, Arizona. We don’t prescribe Cobenfy. Our work is helping people take a careful, supervised look at the psychiatric medications they already take, and, when it makes sense, reduce them slowly.
People come to us with schizophrenia, psychosis, bipolar disorder, depression, and anxiety, often after years on antipsychotics. Care here includes residential support with psychiatric oversight, lab testing, nutrition, counseling, and neurotransmitter support. Medication can have a real role, and no medication decisions are made without you.
Each week you meet with your therapist, the medical director and nursing team, a naturopathic doctor, and your care manager. Our Medical Director describes how the team runs a taper:
“Our medical and nursing teams collaborate closely to monitor each client’s tapering plan, assess progress, and make adjustments as clinically indicated. The team regularly evaluates symptoms, sleep patterns, mood, and overall well-being to support a safe and individualized process.”
Kimberli Galloway, PMHNP-BC, Medical Director
Learn more about psychosis, supervised medication tapering, and residential vs. outpatient tapering.
Talk to our admissions team. Ask about antipsychotic tapering, what a stay looks like, and insurance. Family members are welcome to call.
Call (888) 907-7075Free, confidential consultation
Cobenfy FAQs
Sources:
1. U.S. Food and Drug Administration. FDA Approves Drug with New Mechanism of Action for Treatment of Schizophrenia. News release, September 26, 2024. [cited 2026 Oct 20]
2. Bristol Myers Squibb. COBENFY (xanomeline and trospium chloride) capsules, prescribing information. DailyMed, National Library of Medicine. Updated August 2026. [cited 2026 Oct 20]
3. Kaul I, Sawchak S, Correll CU, et al. Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. Lancet. 2024;403(10422):160-170. doi:10.1016/S0140-6736(23)02190-6. PMID: 38104575. [cited 2026 Oct 20]
4. Kaul I, Sawchak S, Walling DP, et al. Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2024;81(8):749-756. doi:10.1001/jamapsychiatry.2024.0785. PMID: 38691387. [cited 2026 Oct 20]
5. Kaul I, Claxton A, Sauder C, et al. Long-Term Safety and Efficacy of Xanomeline and Trospium Chloride in Schizophrenia: A 52-Week Open-Label Extension Trial. Am J Psychiatry. 2026;183(3):183-192. doi:10.1176/appi.ajp.20241186. PMID: 41634905. [cited 2026 Oct 20]
6. Kaul I, Claxton A, Chaturvedi S, et al. Long-term efficacy, safety, and tolerability of xanomeline and trospium chloride in schizophrenia: A 52-week, open-label trial (EMERGENT-5). Schizophr Res. 2026;288:86-94. doi:10.1016/j.schres.2025.12.015. PMID: 41506001. [cited 2026 Oct 20]
7. Bristol Myers Squibb. Bristol Myers Squibb Announces Topline Results from Phase 3 ARISE Trial Evaluating Cobenfy as an Adjunctive Treatment to Atypical Antipsychotics in Adults with Schizophrenia. Press release, April 22, 2025. [cited 2026 Oct 20]
8. National Institute of Mental Health. Mental Health Medications. [cited 2026 Oct 20]
9. H2-Pharma. SEROQUEL (quetiapine) tablets, prescribing information. DailyMed, National Library of Medicine. [cited 2026 Oct 20]
10. Brannan SK, Sawchak S, Miller AC, Lieberman JA, Paul SM, Breier A. Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia. N Engl J Med. 2021;384(8):717-726. doi:10.1056/NEJMoa2017015. PMID: 33626254. [cited 2026 Oct 20]
11. National Institute of Mental Health. Schizophrenia. [cited 2026 Oct 20]
12. 988 Suicide and Crisis Lifeline. 988lifeline.org. [cited 2026 Oct 20]
13. ClinicalTrials.gov. Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of KarXT in Subjects With Psychosis Associated With Alzheimer’s Disease (ADEPT-3). NCT05980949. [cited 2026 Oct 20]
14. Leucht S, Tardy M, Komossa K, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012;379(9831):2063-2071. doi:10.1016/S0140-6736(12)60239-6. PMID: 22560607. [cited 2026 Oct 20]
Dr. John Motl, M.D.
Dr. Motl is currently certified by the American Board of Psychiatry and Neurology in Psychiatry, and Board eligible in Neurology and licensed in the state of Arizona. He holds a Bachelor of Science degree with a major in biology and minors in chemistry and philosophy. He graduated from Creighton University School of Medicine with a Doctor of Medicine. Dr. Motl has studied Medical Acupuncture at the Colorado School of Traditional Chinese Medicine and at U.C.L.A.
Social Profile: LinkedIn
Diane is an avid supporter and researcher of natural mental health strategies. Diane received her medical writing and science communication certification through Stanford University and has published over 3 million words on the topics of holistic health, addiction, recovery, and alternative medicine. She has proudly worked with the Alternative to Meds Center since its inception and is grateful for the opportunity to help the founding members develop this world-class center that has helped so many thousands regain natural mental health.