VRAYLAR® (cariprazine) Efficacy as an Add-on for MDD Skip to Main Content Contact Medical Information Prescribing Information Patient Site Savings Cards Request Samples Speaker Program Request a Rep Indications Adjunctive MDD Overview Bipolar I Overview Schizophrenia Efficacy Adjunctive MDD Bipolar I Depression Bipolar I Acute Manic or Mixed Episodes Schizophrenia Tolerability & Safety Mechanism of Action Dosing Savings & Resources Access Savings Resources VRAYLAR Videos Speaker Program Request a Rep Proven effective in improving overall depressive symptoms as an antidepressant add-on for MDD Primary endpoint Primary endpoint Anhedonia analysis SF-12 analysis MADRS symptom analysis HAM-A analysis 6-Week Fixed Dose 8-Week Flexible Dose MADRS total score reduction for VRAYLAR + ADT vs placebo + ADT 1,2 6-week fixed dose study (N=751) Pinch to zoom ‡ Not prespecified endpoint and not adjusted for multiplicity. Baseline Mean 31.9 Placebo + ADT (n=249) 32.8 VRAYLAR 1.5 mg/day + ADT (n=250) 32.7 VRAYLAR 3 mg/day + ADT (n=252) VRAYLAR CAN PROVIDE A BOOST of additional antidepressant efficacy at 6 weeks when added to an antidepressant for MDD partial responders Study design 1,3 Duration N Design Doses Studied Control Primary Endpoint 6-Week 751 Fixed Dose 1.5 mg/day + ADT; 3 mg/day + ADT Placebo + ADT Mean change from baseline in MADRS total score at the end of Week 6 8-Week 808 Flexible Dose 1-2 mg/day + ADT Mean VRAYLAR dose was 1.4 mg/day; 2-4.5 mg/day + ADT Mean VRAYLAR dose was 2.6 mg/day Placebo + ADT Mean change from baseline in MADRS total score at the end of Week 8 Both adjunctive MDD studies were randomized, double-blind, placebo-controlled, and evaluated the efficacy and safety of VRAYLAR in adult patients (mean age of 45 years, range 18-65 years) who met DSM-IV-TR or DSM-5 criteria for MDD, with or without symptoms of anxiety, and had an inadequate response to 1 to 3 courses of prior antidepressant (ADT) therapy. § § Inadequate response during antidepressant treatment was defined as less than 50% improvement to antidepressant treatment of adequate dose and duration. Clinical trial patients The VRAYLAR studies included the types of major depressive disorder patients you may see in your practice Baseline characteristics across the 2 pivotal adjunctive MDD studies 1,3,4 Most patients had moderate to severe depressive symptoms at baseline with ADT Baseline mean MADRS total scores: 6-week MDD trial (pooled) = 32.5 VRAYLAR 1.5 mg/day + ADT = 32.8 VRAYLAR 3 mg/day + ADT = 32.7 Placebo + ADT = 31.9 8-week MDD flexible-dose trial VRAYLAR 1-2 mg/day + ADT = 29.0 VRAYLAR 2-4.5 mg/day + ADT = 29.3 Placebo + ADT = 28.9 Patients enrolled were taking the most commonly used antidepressants, including || : sertraline fluoxetine bupropion escitalopram duloxetine citalopram desvenlafaxine venlafaxine had an inadequate response to their first ADT in the current episode across both MDD studies had anhedonia symptoms that were moderate to severe at baseline in the 6-week fixed-dose trial ¶ had anxiety symptoms at baseline in the 6-week fixed-dose trial # || These are not all of the ADTs patients were taking prior to and during the VRAYLAR MDD studies. Please see publications for complete list. 3 ¶ 584/751 (77.8%) patients had MADRS anhedonia subscale scores ≥18. The MADRS anhedonia subscale is the sum of the following items: 1 (apparent sadness), 2 (reported sadness), 6 (concentration difficulties), 7 (lassitude), and 8 (inability to feel). 4 # Overall, 83% of patients had anxiety symptoms at baseline, defined as a score of ≥7 at baseline on the HAM-D anxiety/somatization factor. Anxiety/somatization factor comprises the following 6 items from the HAM-D: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. 3,5 MADRS total score reduction for VRAYLAR + ADT vs placebo + ADT 1,3 8-week flexible dose study (N=808) Pinch to zoom Baseline Mean 28.9 Placebo + ADT (n=264) 29.0 VRAYLAR 1-2 mg/day + ADT (n=273) 29.3 VRAYLAR 2-4.5 mg/day + ADT (n=271) VRAYLAR CAN PROVIDE A BOOST of additional antidepressant efficacy at 8 weeks when added to an antidepressant for MDD partial responders Study design 1,3 Duration N Design Doses Studied Control Primary Endpoint 6-Week 751 Fixed Dose 1.5 mg/day + ADT; 3 mg/day + ADT Placebo + ADT Mean change from baseline in MADRS total score at the end of Week 6 8-Week 808 Flexible Dose 1-2 mg/day + ADT Mean VRAYLAR dose was 1.4 mg/day; 2-4.5 mg/day + ADT Mean VRAYLAR dose was 2.6 mg/day Placebo + ADT Mean change from baseline in MADRS total score at the end of Week 8 Both adjunctive MDD studies were randomized, double-blind, placebo-controlled, and evaluated the efficacy and safety of VRAYLAR in adult patients (mean age of 45 years, range 18-65 years) who met DSM-IV-TR or DSM-5 criteria for MDD, with or without symptoms of anxiety, and had an inadequate response to 1 to 3 courses of prior antidepressant (ADT) therapy. § § Inadequate response during antidepressant treatment was defined as less than 50% improvement to antidepressant treatment of adequate dose and duration. Clinical trial patients The VRAYLAR studies included the types of major depressive disorder patients you may see in your practice Baseline characteristics across the 2 pivotal adjunctive MDD studies 1,3,4 Most patients had moderate to severe depressive symptoms at baseline with ADT Baseline mean MADRS total scores: 6-week MDD trial (pooled) = 32.5 VRAYLAR 1.5 mg/day + ADT = 32.8 VRAYLAR 3 mg/day + ADT = 32.7 Placebo + ADT = 31.9 8-week MDD flexible-dose trial VRAYLAR 1-2 mg/day + ADT = 29.0 VRAYLAR 2-4.5 mg/day + ADT = 29.3 Placebo + ADT = 28.9 Patients enrolled were taking the most commonly used antidepressants, including ‖ : sertraline fluoxetine bupropion escitalopram duloxetine citalopram desvenlafaxine venlafaxine had an inadequate response to their first ADT in the current episode across both MDD studies had anhedonia symptoms that were moderate to severe at baseline in the 6-week fixed-dose trial ¶ had anxiety symptoms at baseline in the 6-week fixed-dose trial # ‖ These are not all of the ADTs patients were taking prior to and during the VRAYLAR MDD studies. Please see publications for complete list. 3 ¶ 584/751 (77.8%) patients had MADRS anhedonia subscale scores ≥18. The MADRS anhedonia subscale is the sum of the following items: 1 (apparent sadness), 2 (reported sadness), 6 (concentration difficulties), 7 (lassitude), and 8 (inability to feel). 4 # Overall, 83% of patients had anxiety symptoms at baseline, defined as a score of ≥7 at baseline on the HAM-D anxiety/somatization factor. Anxiety/somatization factor comprises the following 6 items from the HAM-D: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. 3,5 Observed reduction in MADRS anhedonia subscale score in patients with major depressive disorder at Week 6 in a post-hoc analysis 4 ** Change from baseline in MADRS anhedonia (loss of interest or pleasure) subscale score (N=751) Pinch to zoom Baseline Mean MADRS Anhedonia Subscale Score 19.0 Placebo + ADT (n=249) 19.5 VRAYLAR 1.5 mg/day + ADT (n=250) 19.4 VRAYLAR 3 mg/day + ADT (n=252) These analyses were not prespecified endpoints and were not adjusted for multiplicity. Therefore, treatment differences cannot be regarded as statistically significant. VRAYLAR is indicated in adults as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). 1 MADRS anhedonia subscale is the sum of the following items: 1 (apparent sadness), 2 (reported sadness), 6 (concentration difficulties), 7 (lassitude), and 8 (inability to feel). **This was a post-hoc analysis of the primary endpoint (MADRS change from baseline to Week 6) and was not adjusted for multiplicity. The primary endpoint was change from baseline to Week 6 in MADRS total score. Results of a representative, pivotal, multicenter, randomized, placebo-controlled 6-week trial in adults with MDD (N=751). Patients were randomized in 3 arms: VRAYLAR 1.5 mg, VRAYLAR 3 mg, or placebo + ongoing ADT. 1,4 Study design 4 Duration N Design Doses Studied Control Primary Endpoint 6-Week 751 Fixed Dose 1.5 mg/day + ADT; 3 mg/day + ADT Placebo + ADT Mean change from baseline in MADRS total score at the end of Week 6 A post-hoc analysis of data from 1 multicenter, randomized, placebo-controlled, double-blind study of adults with MDD who had an inadequate response to ADT alone (n=751). Patients in the mITT population (n=751) were either treated with placebo + ADT (n=249), VRAYLAR 1.5 mg/day + ADT, or VRAYLAR 3 mg/day + ADT (n=502). The primary efficacy parameter was change from baseline at 6 weeks in MADRS total score and was analyzed using an MMRM approach. MADRS anhedonia subscale MADRS anhedonia subscale score components 4 The MADRS anhedonia subscale score is composed of 5 items: Apparent sadness Reported sadness Concentration difficulties Lassitude, eg, lack of energy/motivation Inability to feel Observed increase in health-related quality of life in patients with major depressive disorder at Week 6 in a health outcomes measure 3,6 Mean change from baseline to Week 6 in SF-12v2 component summary scores The SF-12v2 measures health-related quality of life and consists of two separate summary scores: Pinch to zoom Placebo (n=249) VRAYLAR 1.5 mg/day + ADT (n=250) VRAYLAR 3 mg/day + ADT (n=252) VRAYLAR is indicated in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). 1 The 12-item Short Form version 2 Health Survey (SF-12v2) was a prespecified Health Outcome Measure in the 6-week adjunctive MDD trial. These data were not adjusted for multiplicity; therefore, treatment differences cannot be regarded as statistically significant. Results from 1 multicenter, randomized, placebo-controlled, double-blind study of adults with MDD who had an inadequate response to ADT alone (n=751). Patients in the mITT population (n=751) were either treated with placebo + ADT (n=249), VRAYLAR 1.5 mg/day + ADT (n=250), or VRAYLAR 3 mg/day + ADT (n=252). The primary efficacy endpoint was change from baseline at 6 weeks in MADRS total score. 3,6 Study design 2,6 Duration N Design Doses Studied Control Primary Endpoint 6-Week 751 Fixed Dose 1.5 mg/day + ADT; 3 mg/day + ADT Placebo + ADT Mean change from baseline in MADRS total score at the end of Week 6 A post-hoc analysis of data from 1 multicenter, randomized, placebo-controlled, double-blind study of adults with MDD who had an inadequate response to ADT alone (n=751). Patients in the mITT population (n=751) were either treated with placebo + ADT (n=249), VRAYLAR 1.5 mg/day + ADT, or VRAYLAR 3 mg/day + ADT (n=502). The primary efficacy parameter was change from baseline at 6 weeks in MADRS total score and was analyzed using an MMRM approach. The 12-Item Short Form version 2 Health Survey (SF-12v2) 6,7 The SF-12v2 survey measures health-related quality of life and consists of the following 2 summary scores, further broken down into 8 subdomains Physical Component Summary (PCS) (Range 0 - 100) Physical Function Limitations of moderate physical activities such as moving a table, pushing a vacuum cleaner, bowling, playing golf, and climbing flights of stairs Role-Physical Limitations of regular daily activities, including work, because of physical health Bodily Pain Extent to which pain interferes with normal work (both outside the home and housework) General Health Rating of overall health Mental Component Summary (MCS) (Range 0 - 100) Vitality Energy levels Social Function Impact of physical/emotional health on engagement in social activities (like visiting friends, relatives, etc) Role-Emotional Limitations of regular daily activities, including work, because of emotional problems Mental Health Rating of overall mental health (calm/peaceful vs down/depressed) Higher scores indicate increased quality of life. Observed reduction in individual MADRS item scores at Week 6 in a post-hoc analysis 1,3 ††‡‡ MADRS items (Scored 0-6) Pinch to zoom Placebo + ADT (n=249) VRAYLAR 1.5 to 3 mg/day + ADT (n=502) These analyses were not prespecified endpoints and were not adjusted for multiplicity. Therefore, treatment differences cannot be regarded as statistically significant. †† This was a post-hoc analysis of the primary endpoint (MADRS change from baseline to Week 6) and was not adjusted for multiple comparisons. ‡‡ The primary endpoint was change from baseline to Week 6 in MADRS total score. Results of a representative, pivotal, multicenter, randomized, placebo-controlled 6-week trial in adults with MDD (N=751). Patients were randomized in 3 arms: cariprazine 1.5 mg, cariprazine 3 mg, or placebo + ongoing ADT. 1,3 Study design 3 Duration N Design Doses Studied Control Primary Endpoint 6-Week 751 Fixed Dose 1.5 mg/day + ADT; 3 mg/day + ADT Placebo + ADT Mean change from baseline in MADRS total score at the end of Week 6 A post-hoc analysis of data from 1 multicenter, randomized, placebo-controlled, double-blind study of adults with MDD who had an inadequate response to ADT alone (n=751). Patients in the mITT population (n=751) were either treated with placebo + ADT (n=249), VRAYLAR 1.5 mg/day + ADT, or VRAYLAR 3 mg/day + ADT (n=502). The primary efficacy parameter was change from baseline at 6 weeks in MADRS total score and was analyzed using an MMRM approach. Observed reduction in anxiety symptom score in patients with major depressive disorder at Week 6 2 Additional efficacy endpoint: Mean change from baseline to Week 6 in HAM-A total score Pinch to zoom Baseline Mean 20.6 Placebo + ADT (n=249) 21.7 VRAYLAR 1.5 mg/day + ADT (n=250) 21.9 VRAYLAR 3 mg/day + ADT (n=252) VRAYLAR is indicated in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). VRAYLAR is not approved for the treatment of anxiety disorders. 1 HAM-A was an additional efficacy endpoint in the 6-week adjunctive MDD trial. This prespecified endpoint was not adjusted for multiplicity. Therefore, treatment differences cannot be regarded as statistically significant. Results from 1 multicenter, randomized, placebo-controlled, double-blind study of adults with MDD who had an inadequate response to ADT alone (n=751). Patients in the mITT population (n=751) were either treated with placebo + ADT (n=249), VRAYLAR 1.5 mg/day + ADT (n=250), or VRAYLAR 3 mg/day + ADT (n=252). The primary efficacy endpoint was change from baseline at 6 weeks in MADRS total score. 2 Study design 2 Duration N Design Doses Studied Control Primary Endpoint 6-Week 751 Fixed Dose 1.5 mg/day + ADT; 3 mg/day + ADT Placebo + ADT Mean change from baseline in MADRS total score at the end of Week 6 The 6-week adjunctive MDD study was randomized, double-blind, placebo-controlled, and evaluated adult patients (mean age of 45 years, range 18 to 65 years) who met DSM IV-TR or DSM-5 criteria for MDD, with or without symptoms of anxiety, and had an inadequate response to 1 to 3 courses of prior antidepressant therapy. §§ §§ Inadequate response during antidepressant treatment was defined as less than 50% improvement to antidepressant treatment of adequate dose and adequate duration. 2 HAM-A scale 8 Hamilton Anxiety Rating Scale (HAM-A) components The HAM-A scale measures the severity of anxiety symptoms and consists of the following 14 items: Anxious mood Tension Fears Insomnia Intellectual (cognitive) Depressed mood General somatic (muscular) General somatic (sensory) Cardiovascular symptoms Respiratory symptoms Gastrointestinal symptoms Genitourinary symptoms Autonomic symptoms Behavior at interview Each item is rated using a 4-point scale: 0 = not present; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. The total score is the sum of all 14 items. Review tolerability & safety Review dosing ADT=antidepressant therapy; DSM= Diagnostic and Statistical Manual of Mental Disorders; HAM-A=Hamilton Anxiety Rating Scale; HAM-D=Hamilton Depression Rating Scale; LS=least squares; MADRS=Montgomery-Asberg Depression Rating Scale; MDD=major depressive disorder; mITT=modified intent-to-treat; MMRM=mixed-effects model for repeated measures; NS=not significant; SF-12v2=Short Form version 2 Health Survey; TR=text revision. INDICATIONS AND USAGE VRAYLAR (cariprazine) is indicated in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of schizophrenia. IMPORTANT SAFETY INFORMATION WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for 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 antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. Contraindication: VRAYLAR is contraindicated in patients with known hypersensitivity. Reactions have included rash, pruritus, urticaria, and reactions suggestive of angioedema. Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic drugs, elderly patients with dementia had a higher incidence of cerebrovascular adverse reactions, including fatalities, vs placebo. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis. Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with antipsychotic drugs. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and monitoring. Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of TD appear, drug discontinuation should be considered. Late-Occurring Adverse Reactions: Adverse reactions may first appear several weeks after initiation of VRAYLAR, probably because plasma levels of cariprazine and its major metabolites accumulate over time. As a result, the incidence of adverse reactions in short-term trials may not reflect the rates after longer-term exposures. Monitor for adverse reactions, including extrapyramidal symptoms (EPS) or akathisia, and patient response for several weeks after starting VRAYLAR and after each dosage increase. Consider reducing the dose or discontinuing the drug. Metabolic Changes: Atypical antipsychotics, including VRAYLAR, have caused metabolic changes, such as: Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Assess fasting glucose before or soon after initiation of treatment, and monitor periodically during long-term treatment. Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after starting an antipsychotic, obtain baseline fasting lipid profile and monitor periodically during treatment. Weight Gain: Weight gain has been observed with VRAYLAR. Monitor weight at baseline and frequently thereafter. Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have been reported with antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically significant decline in WBC and in severely neutropenic patients. Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope, with the greatest risk during initial titration and with dose increases. Monitor orthostatic vital signs in patients predisposed to hypotension and in those with cardiovascular/cerebrovascular diseases. Falls: VRAYLAR may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotics and recurrently for patients on long-term therapy. Seizures: Use VRAYLAR with caution in patients with a history of seizures or with conditions that lower the seizure threshold. Potential for Cognitive and Motor Impairment: Somnolence was reported with VRAYLAR. Caution patients about performing activities requiring mental alertness (eg, operating hazardous machinery or a motor vehicle). Body Temperature Dysregulation: Use VRAYLAR with caution in patients who may experience conditions that increase body temperature (eg, strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics). Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk for aspiration. Drug Interactions: Strong and moderate CYP3A4 inhibitors increase VRAYLAR concentrations, so VRAYLAR dose reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended. Adverse Reactions: The most common adverse reactions in adult clinical trials (≥5% and at least twice the rate of placebo) are listed below: Adjunctive Treatment of Major Depressive Disorder: In 6-week, fixed-dose trials the incidences within the recommended doses (VRAYLAR 1.5 mg/day + antidepressant therapy [ADT] or 3 mg/day + ADT vs placebo + ADT) were akathisia (7%, 10% vs 2%), nausea (7%, 6% vs 3%), and insomnia (9%, 10% vs 5%). In one 8-week flexible-dose trial, incidences within the doses (VRAYLAR 1-2 mg/day + antidepressant therapy [ADT] or 2-4.5 mg/day + ADT vs placebo + ADT) were akathisia (8%, 23% vs 3%), restlessness (8%, 8% vs 3%), fatigue (7%, 10% vs 4%), constipation (2%, 5% vs 2%), nausea (7%, 13% vs 5%), increased appetite (2%, 5% vs 2%), dizziness (4%, 5% vs 2%), insomnia (14%, 16% vs 8%), and extrapyramidal symptoms (12%, 18% vs 5%). Bipolar Mania: The incidences within the recommended dose range (VRAYLAR 3–6 mg/day vs placebo) were EPS (26% vs 12%), akathisia (20% vs 5%), vomiting (10% vs 4%), dyspepsia (7% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%). Bipolar Depression: The incidences within the recommended doses (VRAYLAR 1.5 mg/day or 3 mg/day vs placebo) were nausea (7%, 7% vs 3%), akathisia (6%, 10% vs 2%), restlessness (2%, 7% vs 3%), and EPS (4%, 6% vs 2%). Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5–3 mg/day and 4.5–6 mg/day vs placebo) were EPS (15%, 19% vs 8%) and akathisia (9%, 13% vs 4%). VRAYLAR is available in 0.5 mg, 0.75 mg, 1.5 mg, 3 mg, 4.5 mg, and 6 mg capsules. INDICATIONS AND USAGE VRAYLAR (cariprazine) is indicated for adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults, for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults, for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adult and pediatric patients 10 years of age and older, and for the treatment of schizophrenia in adult and pediatric patients 13 years of age and older. US-VRAA-250443 Please also see full Prescribing Information , including Boxed Warnings. References: VRAYLAR [package insert]. North Chicago, IL: AbbVie Inc.; 2024. Sachs GS, Yeung PP, Rekeda L, Khan A, Adams JL, Fava M. Adjunctive cariprazine for the treatment of patients with major depressive disorder: a randomized, double-blind, placebo-controlled phase 3 study. Am J Psychiatry . 2023;180(3):241-251. doi:10.1176/appi.ajp.20220504 Data on file. AbbVie Inc. McIntyre RS, Malaetic V, Masand P, et al. Effect of adjunctive cariprazine on symptoms of anhedonia in patients with major depressive disorder. Poster presented at: American Society of Clinical Psychopharmacology (ASCP) Annual Meeting; May 30-June 2, 2023. Farabaugh AH, Bitran S, Witte J, et al. Anxious depression and early changes in the HAM-17 anxiety-somatization factor items and antidepressant treatment outcome. Int Clin Psychopharmacol . 2010;25(4):214-217. doi:10.1097/YIC.0b13e328339fbbd Parikh M, Adams JL, Rekeda L, Yee T, Gleeson M, Nabulsi N. Impact of adjunctive cariprazine on quality of life in major depressive disorder: a post hoc analysis. Poster presented at: Psych Congress 2023; September 6-10, 2023; Nashville, TN. Ware JE, Kosinski M, Keller SD. SF-12: How to Score the SF-12 Physical and Mental Health Summary Scales. 2nd ed. The Health Institute, New England Medical Center; 1995. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959;32(1):50-55. doi:10.1111/j.2044-8341.1959.tb00467 Important Safety Information Full Prescribing Information About AbbVie Site Map Accessibility Statement Contact Us Terms of Use Privacy Notice Cookies Settings Your Privacy Choices US-VRAA-240301 If you are a patient, and have any questions, please discuss them with your doctor or healthcare provider. For additional information about VRAYLAR ® , call AbbVie Medical Information toll-free at 1.800.678.1605 . Licensed from Gedeon Richter Plc. © 2025 AbbVie. All rights reserved. VRAYLAR ® and its design are trademarks of Allergan Pharmaceuticals International Limited, an AbbVie company. VRAYPAY SM is a service mark of Allergan Pharmaceuticals International Limited, an AbbVie company. You are about to enter a site that is for U.S. Healthcare Professionals only. By selecting "Yes" below, you certify that you are a Healthcare Professional and that you wish to proceed to the Healthcare Professionals Only section on the AbbVie Medical Information site. Products or treatments described on this site are available in the U.S. but may not be available in all other countries. I am a licensed Healthcare Professional and wish to proceed to the Healthcare Professionals Only AbbVie Medical Information Site. Yes No US-VRAA-240301 WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for 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 antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for 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 antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. INDICATIONS AND USAGE VRAYLAR (cariprazine) is indicated in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of schizophrenia. IMPORTANT SAFETY INFORMATION WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for 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 antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. Contraindication: VRAYLAR is contraindicated in patients with known hypersensitivity. Reactions have included rash, pruritus, urticaria, and reactions suggestive of angioedema. Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic drugs, elderly patients with dementia had a higher incidence of cerebrovascular adverse reactions, including fatalities, vs placebo. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis. Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with antipsychotic drugs. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and monitoring. Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of TD appear, drug discontinuation should be considered. Late-Occurring Adverse Reactions: Adverse reactions may first appear several weeks after initiation of VRAYLAR, probably because plasma levels of cariprazine and its major metabolites accumulate over time. As a result, the incidence of adverse reactions in short-term trials may not reflect the rates after longer-term exposures. Monitor for adverse reactions, including extrapyramidal symptoms (EPS) or akathisia, and patient response for several weeks after starting VRAYLAR and after each dosage increase. Consider reducing the dose or discontinuing the drug. Metabolic Changes: Atypical antipsychotics, including VRAYLAR, have caused metabolic changes, such as: Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Assess fasting glucose before or soon after initiation of treatment, and monitor periodically during long-term treatment. Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after starting an antipsychotic, obtain baseline fasting lipid profile and monitor periodically during treatment. Weight Gain: Weight gain has been observed with VRAYLAR. Monitor weight at baseline and frequently thereafter. Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have been reported with antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically significant decline in WBC and in severely neutropenic patients. Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope, with the greatest risk during initial titration and with dose increases. Monitor orthostatic vital signs in patients predisposed to hypotension and in those with cardiovascular/cerebrovascular diseases. Falls: VRAYLAR may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotics and recurrently for patients on long-term therapy. Seizures: Use VRAYLAR with caution in patients with a history of seizures or with conditions that lower the seizure threshold. Potential for Cognitive and Motor Impairment: Somnolence was reported with VRAYLAR. Caution patients about performing activities requiring mental alertness (eg, operating hazardous machinery or a motor vehicle). Body Temperature Dysregulation: Use VRAYLAR with caution in patients who may experience conditions that increase body temperature (eg, strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics). Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk for aspiration. Drug Interactions: Strong and moderate CYP3A4 inhibitors increase VRAYLAR concentrations, so VRAYLAR dose reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended. Adverse Reactions: The most common adverse reactions in adult clinical trials (≥5% and at least twice the rate of placebo) are listed below: Adjunctive Treatment of Major Depressive Disorder: In 6-week, fixed-dose trials the incidences within the recommended doses (VRAYLAR 1.5 mg/day + antidepressant therapy [ADT] or 3 mg/day + ADT vs placebo + ADT) were akathisia (7%, 10% vs 2%), nausea (7%, 6% vs 3%), and insomnia (9%, 10% vs 5%). In one 8-week flexible-dose trial, incidences within the doses (VRAYLAR 1-2 mg/day + antidepressant therapy [ADT] or 2-4.5 mg/day + ADT vs placebo + ADT) were akathisia (8%, 23% vs 3%), restlessness (8%, 8% vs 3%), fatigue (7%, 10% vs 4%), constipation (2%, 5% vs 2%), nausea (7%, 13% vs 5%), increased appetite (2%, 5% vs 2%), dizziness (4%, 5% vs 2%), insomnia (14%, 16% vs 8%), and extrapyramidal symptoms (12%, 18% vs 5%). Bipolar Mania: The incidences within the recommended dose range (VRAYLAR 3–6 mg/day vs placebo) were EPS (26% vs 12%), akathisia (20% vs 5%), vomiting (10% vs 4%), dyspepsia (7% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%). Bipolar Depression: The incidences within the recommended doses (VRAYLAR 1.5 mg/day or 3 mg/day vs placebo) were nausea (7%, 7% vs 3%), akathisia (6%, 10% vs 2%), restlessness (2%, 7% vs 3%), and EPS (4%, 6% vs 2%). Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5–3 mg/day and 4.5–6 mg/day vs placebo) were EPS (15%, 19% vs 8%) and akathisia (9%, 13% vs 4%). VRAYLAR is available in 0.5 mg, 0.75 mg, 1.5 mg, 3 mg, 4.5 mg, and 6 mg capsules. INDICATIONS AND USAGE VRAYLAR (cariprazine) is indicated for adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults, for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults, for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adult and pediatric patients 10 years of age and older, and for the treatment of schizophrenia in adult and pediatric patients 13 years of age and older. US-VRAA-250443 Please also see full Prescribing Information , including Boxed Warnings.