Primary Efficacy - Bipolar Depression | 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 Unlike some medicines that only treat bipolar I, CAPLYTA treats both bipolar I and II 1-5 For bipolar I and II depression in adults The first and only treatment for depressive episodes associated with bipolar I and bipolar II disorder in adults as monotherapy and adjunctive therapy (with lithium or valproate) 1-5 Clinical studies evaluating adults with a depressive episode associated with bipolar disorder (bipolar depression) 1-5 BP=bipolar. * With lithium or valproate. There are no head-to-head clinical studies comparing the safety and efficacy of these products. This chart is descriptive of the FDA-approved indications in adults with bipolar depression and does not represent all approved indications for each product. Proven antidepressant efficacy at 6 weeks as monotherapy and adjunctive therapy 1,6,7 * †‡ Change from baseline in MADRS total score 1,6,7 †* Monotherapy study placebo-subtracted difference was -4.6 (95% CI, -6.3, -2.8). Mean baseline MADRS total scores for CAPLYTA 42 mg and placebo were 30.8 and 30.3, respectively. Adjunctive therapy study placebo-subtracted difference was -2.4 (95% CI, -4.4, -0.4). Mean baseline MADRS total scores for CAPLYTA 42 mg and placebo were 32.2 and 32.1, respectively. 1 ‡ †The MADRS total score ranges from 0 to 60. Higher scores reflect greater symptom severity. LSM=least squares mean; MADRS=Montgomery-Åsberg Depression Rating Scale. View study design & full chart description Study design Monotherapy study: 6-week study that randomized 381 patients to either CAPLYTA 42 mg or placebo. Patients were generally moderately to markedly ill. Median age was 45 years (range 18 to 72 years). 58% were female, 91% were Caucasian, and 8% were African American. 1 The primary efficacy measure was the change from baseline in MADRS total score. The MADRS is a 10-item clinician-rated scale with total scores ranging from 0 (no depressive features) to 60 (maximum score). Adjunctive therapy study: 6-week study that randomized 529 patients to lithium or valproate with either CAPLYTA 28 mg (two-thirds of the recommended daily dose), CAPLYTA 42 mg, or placebo. Patients were generally moderately to markedly ill. Median age was 46 years (range 18 to 75 years). 58% were female, 88% were Caucasian, and 11% were African American. The treatment effect in the CAPLYTA 28 mg group (vs placebo) was not statistically significant. 1 Full chart description This graph depicts the change from baseline in MADRS total score over 6 weeks for patients receiving CAPLYTA 42 mg or placebo as monotherapy or adjunctive therapy with lithium or valproate. In the monotherapy study, patients on CAPLYTA saw a 16.7-point reduction at 6 weeks compared to 12.1-point reduction with placebo. In the adjunctive therapy study, patients on CAPLYTA saw a 16.9-point reduction at 6 weeks compared to 14.5-point reduction with placebo. MADRS description ‡ †The MADRS total score ranges from 0 to 60. Higher scores reflect greater symptom severity. Each item is scored from 0 to 6, with 0 being the least severe and 6 being most severe. The symptoms scored are: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. 1,8 A higher score represents a more severe condition. Usual cutoffs: 0-6 normal, 7-19 mild, 20-34 moderate, 35-60 severe. CAPLYTA separated from placebo as early as 1 week, continuing to 6 weeks 1,6 Change in MADRS total score in monotherapy study 1,6 CAPLYTA—the maintenance dose is the starting dose ‖ ‡ The primary endpoint was the change from baseline to 6 weeks in score on the Montgomery-Åsberg Depression Rating Scale (MADRS). 2 Baseline MADRS Total Score: CAPLYTA 42 mg: 30.8; placebo 30.3. 1 View full chart description Full chart description This graph depicts the change from baseline in MADRS total score by week over a 6-week period for patients receiving CAPLYTA 42 mg or placebo as monotherapy. Patients on CAPLYTA saw a 16.7-point reduction at 6 weeks compared to 12.1-point reduction with placebo. Improvement observed in individual MADRS item scores in bipolar I and II depression at 6 weeks 9 Improvement in average baseline score in the monotherapy study 9 Limitation: These are exploratory endpoints; results require cautious interpretation. Improvement based on least squares mean change from baseline on individual MADRS items scored 0-6. ¶ ‖ Patients who were at risk for suicide were excluded from the clinical trials. View full chart description This graph depicts the improvement based on least squares mean change from baseline to 6 weeks on individual MADRS items. Patients on CAPLYTA saw a 2.3-point reduction in reported sadness compared to 1.7-point reduction with placebo; 2.1-point reduction in apparent sadness compared to 1.7-point reduction with placebo; 1.6-point reduction in inner tension compared to 1.1-point reduction with placebo; 2.1-point reduction in reduced sleep compared to 1.4-point reduction with placebo; 1.6-point reduction in reduced appetite compared to 1.2-point reduction with placebo; 1.7-point reduction in concentration difficulties compared to 1.4-point reduction with placebo; 1.8-point reduction in lassitude compared to 1.4-point reduction with placebo; 1.8-point reduction in inability to feel compared to 1.3-point reduction with placebo; 1.5-point reduction in pessimistic thoughts compared to 1.1-point reduction with placebo; 0.3-point reduction in suicidal thoughts compared to 0.1‑point reduction with placebo. See the efficacy of CAPLYTA in disease severity Disease Severity 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. Vraylar. Prescribing Information. AbbVie Inc. 3. Seroquel. Prescribing Information. AstraZeneca. 4. Zyprexa. Prescribing Information. Eli Lilly and Company. 5. Latuda. Prescribing Information. Sumitomo Pharma America, Inc. 6. Calabrese JR, Durgam S, Satlin A, et al. Efficacy and safety of lumateperone for major depressive episodes associated with bipolar I or bipolar II disorder: a phase 3 randomized placebo-controlled trial. Am J Psychiatry . Published online September 23, 2021. doi:10.1176/appi.apj.2021.20091339 7. Suppes T, Durgam S, Kozauer SG, et al. Adjunctive lumateperone (ITI-007) in the treatment of bipolar depression: Results from a randomized placebo-controlled clinical trial. Bipolar Disord . 2023;10.1111/bdi.13310. doi:10.1111/bdi.13310 8. Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389. doi:10.1192/bjp.134.4.382 9. McIntyre RS, Durgam S, Kozauer SG, et al. The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses. Eur Neuropsychopharmacol . 2023;68:78-88. doi:10.1016/j.euroneuro.2022.12.012 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.