Lumateperone

CAPLYTA is indicated for: Treatment of schizophrenia in adults [see Clinical Studies (14.1) ] . Treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate [see Clinical Studies (14.2) ] . Adjunctive therapy with antidepressants for the treatment of major depressive disorder (MDD) in adults [see Clinical Studies ( 14.3 ) ]. CAPLYTA is an atypical antipsychotic indicated for: Treatment of schizophrenia in adults. ( 1 ) Treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate. ( 1 ) Adjunctive therapy with antidepressants for the treatment of major depressive disorder (MDD) in adults. ( 1 )

CAPLYTA capsules are available in three strengths: 42 mg: Blue cap and opaque white body imprinted with “ITI-007 42 mg” 21 mg: Opaque white cap and body imprinted with “ITI-007 21 mg” 10.5 mg: Opaque light pink cap and body imprinted with “ITI-007 10.5 mg” Capsules: 42 mg, 21 mg, 10.5 mg ( 3 )

CAPLYTA is contraindicated in patients with history of hypersensitivity reaction to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g. allergic dermatitis, papular rash, and generalized rash), and urticaria. CAPLYTA is contraindicated in patients with history of hypersensitivity reaction to lumateperone or any components of CAPLYTA. ( 4 )

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke and transient ischemic attack). ( 5.3 ) Neuroleptic Malignant Syndrome: If NMS is suspected, immediately discontinue CAPLYTA and provide intensive symptomatic treatment and monitoring. ( 5.4 ) Tardive Dyskinesia: If signs and symptoms of TD occur consider discontinuing CAPLYTA treatment. ( 5.5 ) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. ( 5.6 ) Leukopenia, Neutropenia, and Agranulocytosis : In patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia, perform complete blood counts (CBC). 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 ANC < 1000/mm 3 and monitor closely until the neutropenia resolve. ( 5.7 ) Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure in patients who are vulnerable to hypotension. ( 5.8 ) Seizures: Use cautiously in patients with a history of seizures or with other conditions that lower seizure threshold. ( 5.10 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery and driving a motor vehicle until patients are reasonably certain that therapy with CAPLYTA does not affect them adversely. ( 5.11 )

5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. In an analysis of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, the risk of death in antipsychotic drug-treated patients was 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the incidence of death in antipsychotic-treated patients was about 4.5%, compared to an incidence of about 2.6% in placebo-treated patients. Although the causes of death varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia). CAPLYTA is not approved for the treatment of patients with dementia-related psychosis [see Indications and Usage (1) ] .

5.2 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated pediatric and young adult patients was greater than in placebo-treated patients. There were differences in absolute risk of suicidal thoughts and behaviors across the different uses, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1. Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric* and Adult Patients Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18-24 years old 5 additional patients Decreases Compared to Placebo 25-64 years old 1 fewer patient > 65 years old 6 fewer patients * CAPLYTA is not approved for use in pediatric patients. It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients, especially during the initial few months of anti-depressant drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the health care provider. Consider changing the therapeutic regimen, including possibly discontinuing CAPLYTA, in patients whose depression is persistently worse, or who experience suicidal thoughts or behaviors.

5.3 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials, elderly patients with dementia-related psychosis treated with antipsychotics had a higher incidence of stroke and transient ischemic attack, including fatal stroke compared to those treated with placebo. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis [see Indications and Usage ( 1 ) ] .

5.4 Neuroleptic Malignant Syndrome Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue CAPLYTA and provide intensive symptomatic treatment and monitoring.

5.5 Tardive Dyskinesia Tardive dyskinesia (TD) may develop in patients treated with antipsychotic drugs, including CAPLYTA. TD can develop after a relatively brief treatment period at low dosages and may also occur after discontinuation of treatment. If antipsychotic treatment is discontinued, TD may partially or completely remit. Antipsychotic treatment, however, may suppress or partially suppress the signs and symptoms of TD, and may mask the underlying process. The effect that symptomatic suppression has upon the long-term course of TD is unknown. The TD risk appears to be highest among the elderly, especially elderly women, but it is not possible to predict which patients are likely to develop TD. The TD risk and the likelihood that TD will become irreversible increase with the duration of antipsychotic drug treatment and the cumulative dosage. Periodically reassess the need for continued treatment. If signs and symptoms of TD appear in CAPLYTA-treated patients, consider drug discontinuation. However, some patients may require CAPLYTA treatment despite the presence of TD.

5.6 Metabolic Changes Antipsychotic drugs have caused metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia and Diabetes Mellitus Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. There have been reports of hyperglycemia in patients treated with CAPLYTA. Assess fasting plasma glucose before or soon after initiation of CAPLYTA and monitor periodically during long-term treatment. In pooled data from short-term (4- to 6-week), placebo-controlled trials of adult patients with schizophrenia, mean changes from baseline and the proportion of patients with shifts from normal to greater than normal levels of fasting glucose were similar in CAPLYTA-treated and placebo-treated patients. In an uncontrolled open-label trial of CAPLYTA for up to 1 year in adult patients with stable schizophrenia, the percentages of patients with shifts in fasting glucose and insulin values from normal to high were 8% and 12%, respectively. In this trial, 5% of CAPLYTA-treated patients with normal hemoglobin A1c (<6.5%) at baseline developed elevated levels (≥6.5%) post-baseline. […]

The following adverse reactions are discussed in detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning , Warnings and Precautions (5.1) ] Suicidal Thoughts and Behaviors [see Boxed Warning , Warnings and Precautions (5.2) ] Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-related Psychosis [see Warnings and Precautions (5.3) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.4) ] Tardive Dyskinesia [see Warnings and Precautions (5.5) ] Metabolic Changes [see Warnings and Precautions (5.6) ] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.7) ] Orthostatic Hypotension and Syncope [see Warnings and Precautions (5.8) ] Falls [see Warnings and Precautions (5.9) ] Seizures [see Warnings and Precautions (5.10) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.11) ] Body Temperature Dysregulation [see Warnings and Precautions (5.12) ] Dysphagia [see Warnings and Precautions (5.13) ] Most common adverse reactions in clinical trials (incidence ≥ 5% and greater than twice placebo) were ( 6.1 ): Schizophrenia: somnolence/sedation and dry mouth. Bipolar depression: somnolence/sedation, dizziness, nausea, dry mouth. MDD: dizziness, dry mouth, somnolence/sedation, nausea, fatigue, diarrhea. To report SUSPECTED ADVERSE REACTIONS, contact Intra-Cellular Therapies, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of CAPLYTA has been evaluated in placebo-controlled clinical trials that included 3575 adult patients with schizophrenia, bipolar depression, or major depressive disorder, exposed to one or more CAPLYTA doses. A total of 852 CAPLYTA-treated patients had at least 6 months of treatment and 108 had at least 1 year of treatment with the 42-mg once daily dosage. Adverse Reactions in Patients with Schizophrenia The following adverse reactions are based on the pooled short-term (4- to 6-week), placebo-controlled studies in adult patients with schizophrenia in which CAPLYTA was administered at a dosage of 42 mg once daily (N=406) [see Clinical Studies (14.1) ]. There was no single adverse reaction that led to discontinuation that occurred at a rate of >2% in CAPLYTA-treated patients. The most common adverse reactions (incidence of at least 5% of CAPLYTA-treated patients and greater than twice the rate of placebo-treated patients) were somnolence/sedation and dry mouth. Adverse reactions (incidence of at least 2% in CAPLYTA-treated patients and greater than in placebo-treated patients) are shown in Table 2. Table 2: Adverse Reactions Reported in ≥2% of CAPLYTA-Treated Patients and Greater Incidence Than in Placebo-Treated Patients in 4- to 6-week Schizophrenia Trials CAPLYTA 42 mg (N=406) Placebo (N=412) Somnolence/Sedation 24% 10% Nausea 9% 5% Dry Mouth 6% 2% Dizziness 1 5% 3% Creatine Phosphokinase Increased 4% 1% Fatigue 3% 1% Vomiting 3% 2% Hepatic Transaminases Increased 2 2% 1% Decreased Appetite 2% 1% 1 Dizziness, dizziness postural 2 ALT, AST, “hepatic enzymes” increased, or liver function test abnormal Adverse Reactions in Patients with Bipolar Depression (CAPLYTA Monotherapy) The following adverse reactions are based on the pooled short-term (6-week), placebo-controlled monotherapy bipolar depression studies in adult patients treated with CAPLYTA 42 mg once daily (N=372) [see Clinical Studies (14.2) ] . There was no single adverse reaction leading to discontinuation that occurred at a rate of >2% in CAPLYTA-treated patients. The most common adverse reactions (incidence of at least 5% of CAPLYTA-treated patients and greater than twice the rate in placebo-treated patients) were somnolence/sedation, dizziness, nausea, and dry mouth. Adverse reactions associated with CAPLYTA (incidence of at least 2% in CAPLYTA-treated patients and greater than placebo-treated patients) are shown in Table 3. Table 3: Adverse Reactions Reported in ≥2% of CAPLYTA-Treated Patients and Greater Incidence than in Placebo-Treated Patients in Pooled 6-week Monotherapy Bipolar Depression Trials CAPLYTA 42 mg (N=372) Placebo (N=374) Headache 14% 8% Somnolence/Sedation 13% 3% Dizziness 1 8% 4% Nausea 8% 3% Dry mouth 5% 1% Diarrhea 4% 2% Vomiting 4% 0% Abdominal pain 2 2% 1% Upper respiratory tract infection 2% 1% 1 Dizziness, dizziness postural 2 Abdominal discomfort, abdominal pain, abdominal pain upper and lower Adverse Reactions in Patients with Bipolar Depression (Concomitant Treatment with CAPLYTA and Lithium or Valproate) The adverse reactions below are based on a 6-week, placebo-controlled adjunctive therapy bipolar depression study in adult patients treated with CAPLYTA 42 mg once daily + lithium or valproate OR placebo + lithium or valproate (N=177) [see Clinical Studies (14.2) ]. There was no single adverse reaction leading to discontinuation that occurred at a rate of >2% in patients in the CAPLYTA + lithium or valproate group. The most common adverse reactions (incidence of at least 5% in patients treated with CAPLYTA + lithium or valproate and greater than twice the rate of patients treated with placebo + lithium or valproate) were somnolence/sedation, dizziness, nausea, and dry mouth. Adverse reactions associated with CAPLYTA + lithium or valproate (incidence of at least 2% in patients treated with CAPLYTA + lithium or valproate and greater than with patients treated with placebo + lithium or valproate) are shown in Table 4. Table 4: Adverse Reactions Reported in ≥2% of CAPLYTA-Treated Patients and that Occurred at Greater Incidence than in the Placebo-Treated Patients in a 6-Week Adjunctive Therapy Bipolar Depression Trial CAPLYTA 42 mg + lithium or valproate (N=177) Placebo + lithium or valproate (N=175) Somnolence/Sedation 13% 3% Dizziness 1 11% 2% Nausea 9% 4% Dry mouth 5% 1% Vomiting 4% 0% Diarrhea 3% 2% Upper respiratory tract infection 3% 1% Blurred vision 3% 1% Increased blood prolactin 2% 0% 1 Dizziness, dizziness postural Adverse Reactions in Studies for Adjunctive Treatment of Major Depressive Disorder The following adverse reactions are based on pooled short-term (6-week), placebo-controlled adjunctive therapy MDD studies in adult patients treated with CAPLYTA 42 mg orally once daily and background antidepressant therapy (ADT) or placebo and background ADT (N=483) [see Clinical Studies (14.3) ]. There was no single adverse reaction leading to discontinuation that occurred at an incidence of >2% in patients treated with CAPLYTA and background ADT. The most common adverse reactions (incidence of at least 5% of patients treated with CAPLYTA and background ADT and greater than twice the incidence in patients treated with placebo and background ADT) were dizziness, dry mouth, somnolence/sedation, nausea, fatigue, and diarrhea. Adverse reactions in the adjunctive therapy MDD studies (incidence of at least 2% of patients treated with CAPLYTA and background ADT and greater than in patients treated with placebo and background ADT) are shown in Table 5. […]

CYP3A4 inducers: Avoid concomitant use with CAPLYTA. ( 7.1 ) Strong CYP3A4 inhibitors: Recommended dosage is 10.5 mg once daily. ( 2.2 , 7.1 ) Moderate CYP3A4 inhibitors: Recommended dosage is 21 mg once daily. ( 2.2 , 7.1 )

7.1 Drugs Having Clinically Important Interactions with CAPLYTA Clinically important drug interactions with CAPLYTA are presented in Table 6. Table 6: Clinically Important Drug Interactions with CAPLYTA CYP3A4 Inducers* Prevention or Management Avoid concomitant use of CAPLYTA with CYP3A4 inducers . Clinical Impact Concomitant use of CAPLYTA with CYP3A4 inducers decreases the exposure of lumateperone [see Clinical Pharmacology ( 12.3 ) ]. Moderate or Strong CYP3A4 Inhibitors* Prevention or Management Reduce the CAPLYTA dosage when used concomitantly with moderate or strong CYP3A4 inhibitors [see Dosage and Administration ( 2.2 ) ]. Clinical Impact Concomitant use of CAPLYTA with moderate or strong CYP3A4 inhibitors increases lumateperone exposure [see Clinical Pharmacology ( 12.3 ) ] , which may increase the risk of adverse reactions. Serotonin Reuptake Inhibitors Prevention or Management Increased monitoring for SRI- associated adverse reactions is recommended. Clinical Impact Although no clinically significant drug interactions with adjunctive SSRI/SNRIs in MDD were observed in CAPLYTA clinical trials, CAPLYTA’s moderate serotonin transporter (SERT) activity may increase the risk of SRI-associated adverse reactions (e.g., serotonin syndrome, hyponatremia). * See www.fda.gov/CYPandTransporterInteractingDrugs for examples of CYP3A4 Inducers and Moderate or Strong CYP3A4 Inhibitors

Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 )

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including CAPLYTA, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ). Available data from case reports on CAPLYTA use in pregnant women are insufficient to establish any drug associated risks for birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including CAPLYTA, during pregnancy (see Clinical Considerations ). In animal reproduction studies, no malformations were observed with oral administration of lumateperone to pregnant rats and rabbits during organogenesis at doses up to 2.4 and 9.7 times, respectively, the maximum recommended human dose (MRHD) of 42 mg/day on a mg/m 2 basis. When pregnant rats were administered lumateperone during the period of organogenesis through lactation, the number of perinatal deaths of pups was increased at 4.9 times the MRHD, with no adverse effects on pups at 2.4 times the MRHD (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease Associated Maternal and/or Embryo/fetal Risk: There is risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide. Schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/neonatal Adverse Reactions: Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Animal Data Pregnant rats were treated with oral doses of 3.5, 10.5, 21, and 63 mg/kg/day lumateperone (0.8, 2.4, 4.9, and 14.6 times the MRHD on a mg/m 2 basis) during the period of organogenesis. No malformations were observed with lumateperone at doses up to 2.4 times the MRHD. Findings of decreased body weight were observed in fetuses at 4.9 and 14.6 times the MRHD. Findings of incomplete ossification and increased incidences of visceral and skeletal variations were recorded in fetuses at 14.6 times the MRHD, a dose that induced maternal toxicity. Pregnant rabbits were treated with oral doses of 2.1, 7, and 21 mg/kg/day lumateperone (1.0, 3.2, and 9.7 times the MRHD on a mg/m 2 basis) during the period of organogenesis. Lumateperone did not cause adverse developmental effects at doses up to 9.7 times the MRHD. In a study in which pregnant rats were administered oral doses of 3.5, 10.5, and 21 mg/kg/day lumateperone (0.8, 2.4, and 4.9 times the MRHD on a mg/m 2 basis) during the period of organogenesis and through lactation, the number of live-born pups was decreased at 2.4 and 4.9 times the MRHD, and early postnatal deaths increased at a dose 4.9 times the MRHD. Impaired nursing and decreased body weight gain in pups were observed at 4.9 times, but not at 2.4 times, the MRHD. Pregnant rats were treated with a human metabolite of lumateperone (reduced ketone metabolite) at oral doses of 15, 60, and 100 mg/kg/day (1.2, 19, and 27 times the exposure to this metabolite at the MRHD of lumateperone based on AUC plasma exposure) during the period of organogenesis. This metabolite did not cause adverse developmental effects at a dose 1.2 times the exposure at the MRHD of lumateperone; however, it caused an increase in visceral malformations (cleft palate) at 27 times and skeletal malformations at 19 times the exposure at the MRHD of lumateperone, a dose that induced maternal toxicity.

8.2 Lactation Risk Summary Lumateperone and its metabolites are present in human breast milk in low amounts. In a clinical lactation study, lumateperone was detected in human milk at an estimated daily infant dose 0.0004 mg/kg, with a relative infant dose (RID) of 0.06% the maternal weight-adjusted dosage. Several major circulating metabolites were similarly detected in breast milk in low amounts; however, aniline metabolites were not present in milk or maternal plasma at quantifiable levels (see Data ) . There are no data on the effects of lumateperone on the breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CAPLYTA and any potential adverse effects on the breastfed child from CAPLYTA or from the underlying maternal condition. Data A lactation study in 17 lactating women evaluated the concentrations of lumateperone and its metabolites in plasma and mature breast milk following a single dose of 42 mg CAPLYTA. The estimated daily infant dose of lumateperone in human milk was 0.0004 mg/kg/day (with assumed average milk consumption of 200 ml/kg/day). The mean relative infant dose (RID) (with assumed mean milk consumption of 200 mL/kg/day and average maternal weight of 71 kg) was 0.06% of the maternal weight-adjusted dosage. Several major circulating metabolites were also present in breast milk at estimated daily infant dose of 0.0004 mg/kg/day. Aniline metabolites were not present in milk or maternal plasma at quantifiable levels.

8.3 Females and Males of Reproductive Potential Infertility Based on findings from animal studies, lumateperone may impair male and female fertility [see Nonclinical Toxicology (13.1) ].

8.4 Pediatric Use Safety and effectiveness of CAPLYTA have not been established in pediatric patients. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions (5.2) ].

8.5 Geriatric Use Controlled clinical studies of CAPLYTA for the treatment of schizophrenia and as adjunctive therapy with antidepressants for the treatment of MDD did not include any patients aged 65 or older to determine whether or not they respond differently from younger adult patients. Among the CAPLYTA-treated patients in clinical studies for the treatment of depressive episodes associated with bipolar depression, 20 (6%) were 65 to 74 years of age, and none were 75 years of age or older [see Clinical Studies (14.2) ]. These clinical studies did not include sufficient numbers of patients aged 65 years of age or older to determine whether or not they respond differently from younger adult patients. Antipsychotic drugs increase the risk of death in elderly patients with dementia-related psychosis. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions ( 5.1 ) and ( 5.3 ) ] . […]

The mechanism of action of lumateperone for the treatment of schizophrenia in adults, for the treatment of depressive episodes associated with bipolar depression (as monotherapy or as adjunctive therapy with lithium or valproate), and as adjunctive therapy with antidepressants for the treatment of MDD is unknown. However, the mechanism of action of lumateperone for these uses could be mediated through a combination of antagonist activity at central serotonin 5-HT 2A receptors, and partial agonist activity at central dopamine D 2 receptors.