Sponsored by Bristol Myers Squibb
Fines Shaw, DNP, PMHNP was paid honoraria by Bristol Myers Squibb.
For people living with schizophrenia, it can be difficult to talk about their condition and symptoms they may be experiencing. Stigma, shame, or the feeling of not wanting to let down their loved ones or even medical professionals can all become barriers to honest conversations, which in turn can impact their journey with schizophrenia, and ultimately make it harder to find an appropriate treatment option for them.
As nurses and nurse practitioners, it is our responsibility to create an environment that allows for dialogue to help our patients feel comfortable opening up about the challenges they’re facing. This may include socioeconomic struggles that are affecting their access to care or elements of their condition that may be interfering with their daily lives. We’re uniquely positioned to listen, which has helped me build trust with my patients and, in turn, given them the confidence to share symptoms or other challenges that I would not have known otherwise.
Understanding Unique Challenges of Schizophrenia
Because schizophrenia is a complex illness that remains stigmatized, patients may avoid talking about what is affecting them. This can include negative symptoms like lack of emotional affect and social withdrawal, positive symptoms like hallucinations and delusions, and general psychopathology symptoms like impaired attention and deficits in decision-making.
Many people living with schizophrenia experience symptoms, which can in turn lead to feelings of isolation and shame causing disruptions to daily life, like employment or trying to keep up routines and relationships. These symptoms can in turn exacerbate feelings of isolation and shame causing significant disruptions to daily life, whether maintaining employment or trying to keep up with routines and relationships.
Listening Builds Trust
As stated, trust is fundamental to our work as nurses and nurse practitioners. It enables us to listen to our patients without judgment and helps let them know they’re in a safe space where they can be more candid about how they’re doing.
In my clinical practice, I strive to create a safe, supportive and nonjudgmental environment where patients feel comfortable sharing their experiences, as well as their symptoms. I intentionally work to normalize these conversations, emphasizing that they’re not alone in their experiences and don’t have to feel ashamed. When appropriate, I share how mental illnesses have touched my own family, including my mother and daughter, who both live with schizophrenia. I explain that, despite the challenges they’ve faced, they have demonstrated resilience and ability to navigate their disease journey. Sharing this perspective with my patients can help them feel less alone and often opens the door to more honest and meaningful conversations.
My goal is for patients to feel heard, validated and understood, and to recognize that discussing their symptoms openly is a sign of strength rather than weakness. When this happens, it can unlock new information that allows us to holistically understand their situation and tailor treatment options for them.
Building trust doesn’t happen overnight, though. For one of my patients in particular, it took time for him to open up about symptoms that were significantly impacting his daily life. This made me start thinking differently about his treatments. Through a lot of open dialogue and honest conversation about options, including the potential benefits and risks, we ultimately decided to try COBENFY™ (xanomeline and trospium chloride), a twice-daily oral medication for adults with schizophrenia.[i]
It is not known if COBENFY is safe and effective in children. Please see Important Safety Information below and U.S. Full Prescribing Information and Patient Information for COBENFY.
What is COBENFY?
Unlike other schizophrenia treatments, COBENFY does not bind to dopamine D2 receptors. It is a unique combination of xanomeline, a dual M1– and M4-preferring muscarinic receptor agonist, and trospium chloride, a muscarinic antagonist. Xanomeline binds to muscarinic receptors M1 and M5 with comparable affinity and exhibits higher agonist activity at the M1 and M4 receptors. Trospium chloride antagonizes the muscarinic receptors primarily in the peripheral tissues. While the exact mechanism of action of COBENFY is unclear, its efficacy is thought to be due to the agonist activity of xanomeline at M1 and M4 muscarinic acetylcholine receptors in the central nervous system.[ii]
The EMERGENT clinical trial program evaluated COBENFY in more than 1,250 patients across five clinical trials, including three 5-week placebo-controlled efficacy and safety trials* and two open-label trials evaluating long-term safety and tolerability for up to one year.[iii],[iv],[v],[vi],[vii] EMERGENT-1 (N=182, phase 2), EMERGENT-2 (N=252, phase 3), and EMERGENT-3 (N=253, phase 3) were randomized, double-blind, placebo controlled studies that assessed the safety and efficacy of COBENFY. The primary endpoint in all short-term studies was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 5 vs placebo.
In the Phase 3 EMERGENT-2 and EMERGENT-3 trials specifically, which supported the FDA approval of COBENFY, patients saw a 9.6-point reduction (-21.2 COBENFY vs. -11.6 placebo, P < 0.001) and an 8.4-point reduction in (-20.6 COBENFY vs. -12.2 placebo, P < 0.001) in PANSS total score, respectively, compared to placebo at week five. As assessed by the PANSS total score in the pooled, mITT population, patients treated with COBENFY experienced a two times greater reduction in PANSS total score compared with placebo (-19.5 v. -9.6) at week 5. Endpoints in the pooled analysis were analyzed descriptively and considered exploratory.
The safety and tolerability profile of COBENFY has also been established across acute and long-term trials. The most common adverse reactions (≥ 5 % and at least twice placebo) included nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease (GERD). Additional adverse reactions include dry mouth, somnolence, blurred vision, salivary hypersecretion, orthostatic hypotension, cough and extrapyramidal symptoms (non-akathisia).
COBENFY has warnings and precautions for: risk of urinary retention, risk of use in patients with hepatic impairment, risk of use in patients with biliary disease, decreased gastrointestinal motility, risk of angioedema, risk of use in patients with narrow-angle glaucoma, increases in heart rate, anticholinergic adverse reactions in patients with renal impairment, and central nervous system effects. Please see Important Safety Information and U.S. Full Prescribing Information, including contraindications, below.
With my patient I previously mentioned, we have seen an improvement in his overall schizophrenia symptoms since starting on medication. Though each person’s experience may be different and results may vary, his story reminds me why it’s so important to have open dialogue with patients and work collaboratively to find the treatment that is right for them.
If it weren’t for listening to my patient and building that trust, the path to finding the right treatment for them could have been prolonged. This kind of trust requires give and take though, so being honest with them about the side effects they might experience from treatment is also critical to ensuring they are confident in the choice we’re making.
If my patients do experience side effects, I always tell them to contact me right away, and as long as we continue to have an open dialogue, we can work together to navigate and help address them when they arise.
Turning Trust into Ongoing Care
As healthcare professionals on the front lines of patient care, we know better than anyone that, once trust is established, that doesn’t mean the work is done—that trust must be maintained. The way I personally handle that is holding both myself and my patients accountable to the same standards of honesty and respect, ensuring that both of us are listening and on the same page—even when things get difficult.
I am confident that almost every nurse and nurse practitioner will already have their own unique ways to actively build trust and understand the symptoms of their patients. From listening to learning to continually fostering those relationships, we can help our patients determine which treatment option may be right for them. And, in my experience, for appropriate patients that could be COBENFY.
To learn more about COBENFY, see additional findings from the clinical trials and explore other resources to determine if COBENFY could be right for your patients, visit COBENFYHCP.com.
*Patients who were newly diagnosed or were experiencing their first treated episode of schizophrenia were excluded
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INDICATION
COBENFY™ (xanomeline and trospium chloride) is indicated for the treatment of schizophrenia in adults.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
COBENFY is contraindicated in patients with:
- urinary retention
- moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment
- gastric retention
- history of hypersensitivity to COBENFY or trospium chloride. Angioedema has been reported with COBENFY and trospium chloride.
- untreated narrow-angle glaucoma
WARNINGS AND PRECAUTIONS
Risk of Urinary Retention: COBENFY can cause urinary retention. Geriatric patients and patients with clinically significant bladder outlet obstruction and incomplete bladder emptying (e.g., patients with benign prostatic hyperplasia (BPH), diabetic cystopathy) may be at increased risk of urinary retention.
COBENFY is contraindicated in patients with pre-existing urinary retention and is not recommended in patients with moderate or severe renal impairment.
In patients taking COBENFY, monitor for symptoms of urinary retention, including urinary hesitancy, weak stream, incomplete bladder emptying, and dysuria. Instruct patients to be aware of the risk and promptly report symptoms of urinary retention to their healthcare provider. Urinary retention is a known risk factor for urinary tract infections. In patients with symptoms of urinary retention, consider reducing the dose of COBENFY, discontinuing COBENFY, or referring patients for urologic evaluation as clinically indicated.
Risk of Use in Patients with Hepatic Impairment: Patients with hepatic impairment have higher systemic exposures of xanomeline, a component of COBENFY, compared to patients with normal hepatic function, which may result in increased incidence of COBENFY-related adverse reactions.
COBENFY is contraindicated in patients with moderate or severe hepatic impairment. COBENFY is not recommended in patients with mild hepatic impairment.
Assess liver enzymes prior to initiating COBENFY and as clinically indicated during treatment.
Risk of Use in Patients with Biliary Disease: In clinical studies with COBENFY, transient increases in liver enzymes with rapid decline occurred, consistent with transient biliary obstruction due to biliary contraction and possible gallstone passage.
COBENFY is not recommended for patients with active biliary disease such as symptomatic gallstones. Assess liver enzymes and bilirubin prior to initiating COBENFY and as clinically indicated during treatment. The occurrence of symptoms such as dyspepsia, nausea, vomiting, or upper abdominal pain should prompt assessment for gallbladder disorders, biliary disorders, and pancreatitis, as clinically indicated.
Discontinue COBENFY in the presence of signs or symptoms of substantial liver injury such as jaundice, pruritus, or alanine aminotransferase levels more than five times the upper limit of normal or five times baseline values.
Decreased Gastrointestinal Motility: COBENFY contains trospium chloride. Trospium chloride, like other antimuscarinic agents, may decrease gastrointestinal motility. Administer COBENFY with caution in patients with gastrointestinal obstructive disorders because of the risk of gastric retention. Use COBENFY with caution in patients with conditions such as ulcerative colitis, intestinal atony, and myasthenia gravis.
Risk of Angioedema: Angioedema of the face, lips, tongue, and/or larynx has been reported with COBENFY and trospium chloride, a component of COBENFY. In one case, angioedema occurred after the first dose of trospium chloride. Angioedema associated with upper airway swelling may be life-threatening. If involvement of the tongue, hypopharynx, or larynx occurs, discontinue COBENFY and initiate appropriate therapy and/or measures necessary to ensure a patent airway. COBENFY is contraindicated in patients with a history of hypersensitivity to trospium chloride.
Risk of Use in Patients with Narrow-angle Glaucoma: Pupillary dilation may occur due to the anticholinergic effects of COBENFY. This may trigger an acute angle closure attack in patients with anatomically narrow angles. In patients known to have anatomically narrow angles, COBENFY should only be used if the potential benefits outweigh the risks and with careful monitoring.
Increases in Heart Rate: COBENFY can increase heart rate. Assess heart rate at baseline and as clinically indicated during treatment with COBENFY.
Anticholinergic Adverse Reactions in Patients with Renal Impairment: Trospium chloride, a component of COBENFY, is substantially excreted by the kidney. COBENFY is not recommended in patients with moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) <60 mL/min). Systemic exposure of trospium chloride is higher in patients with moderate and severe renal impairment. Therefore, anticholinergic adverse reactions (including dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention) are expected to be greater in patients with moderate and severe renal impairment.
Central Nervous System Effects: Trospium chloride, a component of COBENFY, is associated with anticholinergic central nervous system (CNS) effects. A variety of CNS anticholinergic effects have been reported with trospium chloride, including dizziness, confusion, hallucinations, and somnolence. Monitor patients for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how COBENFY affects them. If a patient experiences anticholinergic CNS effects, consider dose reduction or drug discontinuation.
Most Common Adverse Reactions (≥5% and at least twice placebo): nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease.
Use in Specific Populations:
- Moderate or Severe Renal Impairment: Not recommended
- Mild Hepatic Impairment: Not recommended
Pregnancy and Lactation: There is a pregnancy exposure registry that monitors outcomes in women exposed to psychiatric medications, including COBENFY, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling 1-866-961-2388 or visiting https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/.
There are no available data on COBENFY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Additionally, there are no data on the presence of xanomeline or trospium in human milk, the effects on the breastfed infant, or the effects on milk production. However, xanomeline and trospium are present in animal milk, suggesting they may also be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for COBENFY and any potential adverse effects on the breastfed infant from COBENFY or the underlying maternal condition.
COBENFY (xanomeline and trospium chloride) is available in 50mg/20mg, 100mg/20mg, and 125mg/30mg capsules.
Please see U.S. Full Prescribing Information, including Patient Information.
Cobenfy and the Cobenfy logo are trademarks of Karuna Therapeutics, Inc., a Bristol Myers Squibb company.
© 2026 Bristol-Myers Squibb Company.
1629-US-2600202 06/26
1 COBENFY. Prescribing Information. Bristol-Myers Squibb Company; 2026.
2 Dean B, Bakker G, Ueda HR, Tobin AB, Brown A, Kanaan RAA. A growing understanding of the role of muscarinic receptors in the molecular pathology and treatment of schizophrenia. Front Cell Neurosci. 2023;17:1124333.
3 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.
4 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.
5 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.
6 Kaul I, Claxton A, Sauder C, et al. Long-term safety and efficacy of xanomeline and trospium chloride in schizophrenia: results from the 52-week, open-label EMERGENT-4 trial. Poster presented at: Psych Congress; October 29-November 2, 2024; Boston, MA.
7 Kaul I, Claxton A, Sauder C, et al. Long-term safety, tolerability, and efficacy of xanomeline and trospium chloride in people with schizophrenia: results from the 52-week, open-label EMERGENT-5 trial. Poster presented at: Psych Congress; October 29- November 2, 2024; Boston, MA.
- Listening First: The Role of Trust in Schizophrenia Care - July 7, 2026