Primary Efficacy - Schizophrenia | CAPLYTA® (lumateperone) Skip to Content Now approved for adults with major depressive disorder  (adjunctive) For US Healthcare Professionals For US Healthcare Professionals For Patients Adjunctive MDD Bipolar Depression Schizophrenia For Pharmacists Prescribing Information Request a Rep Menu Disease States Major Depressive Disorder Bipolar I & II Depression Schizophrenia Efficacy Adjunctive MDD Primary: MADRS Total Score MADRS Individual Scores MADRS Anxious Distress Bipolar I & II Depression Primary Efficacy Disease Severity Quality of Life Bipolar II Pooled Data Schizophrenia Primary Efficacy PANSS Subscales Prosocial Subscale Safety & Tolerability Adjunctive MDD Most Common Adverse Reactions Weight & Metabolic Effects Sexual Side Effects & EPS Bipolar I & II Depression EPS and Akathisia Weight & Metabolic Effects Most Common Adverse Reactions Schizophrenia EPS and Akathisia Weight & Metabolic Effects Most Common Adverse Reactions Long-term Data Dosing & MOA Dosing MOA Savings & Resources Coverage CAPLYTA withMe Resources Savings Card For US Healthcare Professionals For Patients Adjunctive MDD Bipolar Depression Schizophrenia CAPLYTA demonstrated statistically superior improvement vs placebo in 2 clinical trials 1 For schizophrenia in adults Significant improvement in PANSS total score over 4 weeks in Study 1 1 * Change in baseline in PANSS total score 1,2 This study was not designed to allow for efficacy comparison of CAPLYTA and risperidone. Risperidone was included for assay sensitivity. 1,3 Baseline PANSS Total Scores: CAPLYTA 42 mg: 88.1; risperidone 4 mg: 86.1; placebo: 86.3. 1,2 LSM=least squares mean; PANSS=Positive and Negative Syndrome Scale. * The PANSS is a 30-item scale used to measure symptoms of schizophrenia. Each item is rated by a clinician on a 7-point scale. A score of 1 indicates the absence of symptoms, and a score of 7 indicates extremely severe symptoms. The PANSS total score may range from 30 to 210, with higher scores reflecting greater overall symptom severity. 1 View study design & full chart description Study design A randomized, double-blind, placebo-controlled, multicenter, inpatient clinical trial that enrolled patients with an acute exacerbation of schizophrenia. The primary endpoint was change from baseline in the PANSS total score at 4 weeks compared to placebo. Patients were screened for up to a 7-day drug-free period. All treatments were dosed as oral monotherapy once daily in the morning for 4 weeks. 1,2 Study 1 randomized 335 patients to either CAPLYTA 42 mg, CAPLYTA 84 mg, active comparator, or placebo in a 1:1:1:1 fashion. Patients were generally moderately to markedly ill. Median age was 42 years (range 20 to 55 years). 17% were female, 19% were Caucasian, and 78% were African American. The treatment effect in the CAPLYTA 84 mg group (vs placebo) was not statistically significant. 1,3 Full chart description This graph depicts the change in total PANSS score over 4 weeks for patients receiving risperidone 4 mg, CAPLYTA 42 mg, or placebo. Baseline PANSS total scores were 86.1 for risperidone, 88.1 for CAPLYTA, and 86.3 for placebo. At 4 weeks, patients on risperidone saw a 13.4-point reduction in PANSS total score, patients on CAPLYTA saw a 13.2-point reduction in PANSS total score, and patients on placebo saw a 7.4-point reduction in PANSS total score. CAPLYTA showed a 5.8-point reduction in PANSS total score over placebo. CAPLYTA separated from placebo as early as week 1 in Study 2 1,3,4 Change from baseline in PANSS total score over 4 weeks 1,3,4 Limitation: The weekly time points prior to 4 weeks were not powered for statistical comparison and are descriptive only. Baseline PANSS Total Scores: CAPLYTA 42 mg: 90.0; placebo: 89.0 1 ‡ P <0.05 vs placebo. 3 View study design & full chart description Study design A randomized, double-blind, placebo-controlled, multicenter, inpatient clinical trial that enrolled patients with an acute exacerbation of schizophrenia. The primary endpoint was change from baseline in the PANSS total score at 4 weeks compared to placebo. Patients were screened for up to a 7-day drug-free period. All treatments were dosed as oral monotherapy once daily in the morning for 4 weeks. 1,4 Study 2 randomized 450 patients to either CAPLYTA 28 mg, CAPLYTA 42 mg, or placebo in a 1:1:1 fashion. Patients were generally moderately to markedly ill. Median age was 44 years (range 19 to 60 years); 23% were female, 26% were Caucasian, and 66% were African American. The treatment effect in the CAPLYTA 28 mg group (vs placebo) was not statistically significant. 1,3 Full chart description This graph depicts the change from baseline in PANSS total score over 28 days for patients receiving CAPLYTA 42 mg or placebo. Baseline PANSS total scores were 90.0 for CAPLYTA, and 89.0 for placebo. At 4 weeks, CAPLYTA showed a 4.2-point reduction in baseline PANSS total score over placebo. CAPLYTA demonstrated significant improvement in clinical global impression-severity (CGI-S) scores 4‖ CGI-S was a secondary endpoint 3 Patients on CAPLYTA 42 mg saw a 0.8 improvement in CGI-S score vs 0.5 on placebo ( P <0.05). Baseline CGI-S scores (mean) were 4.8 for CAPLYTA 42 mg and placebo. 3 ‖ The CGI-S asks the clinician how mentally ill the patient is, which is rated on the following 7-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. 5 See CAPLYTA secondary endpoint data in schizophrenia PANSS Subscales Frequently Asked Questions Was risperidone an active control or active comparator in Study 1? In Study 1, risperidone was an active comparator and included for assay sensitivity. 2 The study was not designed to allow for efficacy comparison of CAPLYTA and risperidone. 1 Can CAPLYTA be used for first break psychosis in schizophrenia, including first-episode psychosis? CAPLYTA is indicated for the treatment of schizophrenia in adults. CAPLYTA may be used at any point across the spectrum and severity of disease. 1 Indications CAPLYTA is indicated in adults for adjunctive therapy along with antidepressants for the treatment of major depressive disorder (MDD); the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate; and the treatment of schizophrenia. Important Safety Information BOXED WARNINGS: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients. Contraindications: CAPLYTA is contraindicated in patients with a history of hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria. Warnings & Precautions: Antipsychotic drugs have been reported to cause: Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis , including stroke and transient ischemic attack. See Boxed WARNING above. Neuroleptic Malignant Syndrome , which is a potentially fatal reaction. Signs and symptoms include hyperpyrexia, muscle rigidity, delirium, autonomic instability, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation of CAPLYTA and provide intensive symptomatic treatment and monitoring. Tardive Dyskinesia (TD) may develop in patients treated with antipsychotic drugs, including CAPLYTA. TD can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. The TD risk appears to be highest in elderly women. The likelihood that TD will become irreversible increases with the duration of the antipsychotic drug treatment and cumulative dose. If signs and symptoms of TD appear, consider discontinuing CAPLYTA if clinically appropriate. Metabolic Changes , including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment. Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases) . Perform complete blood counts in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing CAPLYTA if clinically significant decline in WBC occurs in absence of other causative factors. Discontinue CAPLYTA in patients with clinically significant neutropenia or absolute neutrophil count <1000/mm 3 and monitor closely until neutropenia resolves. Orthostatic Hypotension and Syncope . Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension. Falls . CAPLYTA may cause somnolence, postural hypotension, and motor and/or sensory instability, which may lead to falls and, consequently, fractures and other injuries. Assess patients for fall risk when initiating treatment and periodically during long-term treatment. Seizures . Use CAPLYTA cautiously in patients with a history of seizures or with conditions that lower seizure threshold. Potential for Cognitive and Motor Impairment . Advise patients to use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them. Body Temperature Dysregulation . Use CAPLYTA with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics. Dysphagia . Use CAPLYTA with caution in patients at risk for aspiration. Drug Interactions: Avoid concomitant use with CYP3A4 inducers. Reduce dose for concomitant use with strong CYP3A4 inhibitors (10.5 mg) or moderate CYP3A4 inhibitors (21 mg). Increased monitoring for serotonin reuptake inhibitor (SRI)‑associated adverse reactions is recommended when used with SRIs; including in geriatric patients who may be at greater risk for clinically significant hyponatremia. Special Populations: Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Reduce dose for patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment (21 mg). Adverse Reactions: The most common adverse reactions in clinical trials (≥5% and greater than twice placebo) with CAPLYTA vs placebo were: Major Depressive Disorder (Adjunctive therapy): dizziness (17% vs 5%), dry mouth (13% vs 3%), somnolence/sedation (12% vs 2%), nausea (9% vs 4%), fatigue (8% vs 2%), and diarrhea (5% vs 1%). Bipolar Depression (Monotherapy, Adjunctive therapy): somnolence/sedation (13% vs 3%, 13% vs 3%), dizziness (8% vs 4%, 11% vs 2%), nausea (8% vs 3%, 9% vs 4%), and dry mouth (5% vs 1%, 5% vs 1%). Schizophrenia: somnolence/sedation (24% vs 10%) and dry mouth (6% vs 2%). CAPLYTA is available in 42 mg, 21 mg, and 10.5 mg capsules. Indications CAPLYTA is indicated in adults for adjunctive therapy along with antidepressants for the treatment of major depressive disorder (MDD); the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate; and the treatment of schizophrenia. US‑CAP‑2500828 Please see full Prescribing Information , including Boxed WARNINGS. Savings Card Local Coverage  Finder Samples Indications CAPLYTA is indicated in adults for adjunctive therapy along with antidepressants for the treatment of major depressive disorder (MDD); the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate; and the treatment of schizophrenia. Important Safety Information BOXED WARNINGS: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients. Contraindications: CAPLYTA is contraindicated in patients with a history of hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria. Warnings & Precautions: Antipsychotic drugs have been reported to cause: Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis , including stroke and transient ischemic attack. See Boxed WARNING above. Neuroleptic Malignant Syndrome , which is a potentially fatal reaction. Signs and symptoms include hyperpyrexia, muscle rigidity, delirium, autonomic instability, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation of CAPLYTA and provide intensive symptomatic treatment and monitoring. Tardive Dyskinesia (TD) may develop in patients treated with antipsychotic drugs, including CAPLYTA. TD can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. The TD risk appears to be highest in elderly women. The likelihood that TD will become irreversible increases with the duration of the antipsychotic drug treatment and cumulative dose. If signs and symptoms of TD appear, consider discontinuing CAPLYTA if clinically appropriate. Metabolic Changes , including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment. Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases) . Perform complete blood counts in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing CAPLYTA if clinically significant decline in WBC occurs in absence of other causative factors. Discontinue CAPLYTA in patients with clinically significant neutropenia or absolute neutrophil count <1000/mm 3 and monitor closely until neutropenia resolves. Orthostatic Hypotension and Syncope . Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension. Falls . CAPLYTA may cause somnolence, postural hypotension, and motor and/or sensory instability, which may lead to falls and, consequently, fractures and other injuries. Assess patients for fall risk when initiating treatment and periodically during long-term treatment. Seizures . Use CAPLYTA cautiously in patients with a history of seizures or with conditions that lower seizure threshold. Potential for Cognitive and Motor Impairment . Advise patients to use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them. Body Temperature Dysregulation . Use CAPLYTA with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics. Dysphagia . Use CAPLYTA with caution in patients at risk for aspiration. Drug Interactions: Avoid concomitant use with CYP3A4 inducers. Reduce dose for concomitant use with strong CYP3A4 inhibitors (10.5 mg) or moderate CYP3A4 inhibitors (21 mg). Increased monitoring for serotonin reuptake inhibitor (SRI)‑associated adverse reactions is recommended when used with SRIs; including in geriatric patients who may be at greater risk for clinically significant hyponatremia. Special Populations: Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Reduce dose for patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment (21 mg). Adverse Reactions: The most common adverse reactions in clinical trials (≥5% and greater than twice placebo) with CAPLYTA vs placebo were: Major Depressive Disorder (Adjunctive therapy): dizziness (17% vs 5%), dry mouth (13% vs 3%), somnolence/sedation (12% vs 2%), nausea (9% vs 4%), fatigue (8% vs 2%), and diarrhea (5% vs 1%). Bipolar Depression (Monotherapy, Adjunctive therapy): somnolence/sedation (13% vs 3%, 13% vs 3%), dizziness (8% vs 4%, 11% vs 2%), nausea (8% vs 3%, 9% vs 4%), and dry mouth (5% vs 1%, 5% vs 1%). Schizophrenia: somnolence/sedation (24% vs 10%) and dry mouth (6% vs 2%). CAPLYTA is available in 42 mg, 21 mg, and 10.5 mg capsules. Indications CAPLYTA is indicated in adults for adjunctive therapy along with antidepressants for the treatment of major depressive disorder (MDD); the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate; and the treatment of schizophrenia. US‑CAP‑2500828 Please see full Prescribing Information , including Boxed WARNINGS. References: 1. CAPLYTA Prescribing Information. 2. Lieberman JA, Davis RE, Correll CU, et al. CAPLYTA for the treatment of schizophrenia: a 4-week randomized, double-blind, controlled trial. Biol Psychiatry . 2016;79(12):952-961. doi:10.1016/j.biopsych.2015.08.026 3. Data on File (REF-00332, REF-00360). 4. Correll CU, Davis RE, Weingart M, et al. Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical trial. JAMA Psychiatry . 2020;77(4):349-358. doi:10.1001/jamapsychiatry.2019.4379 5. Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont) . 2007;4(7):28-37. Terms of Use Privacy Policy Cookie Policy Contact Us Disclosures ITCI Corporate Site Sitemap Your Privacy Choices AdChoices Opt-out © Johnson & Johnson and its affiliates 2025. CAPLYTA and LET IN THE LYTE are trademarks of Johnson & Johnson and its affiliates. Trademarks listed are the property of their respective owners. 10/25 US-CAP-2500203 Important Safety Information See Full ISI BOXED WARNINGS: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients.