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REXULTI® (brexpiprazole) + Antidepressants: Better Together

For patients with MDD who have a partial response

REXULTI® (brexpiprazole) + Antidepressants: Better Together

For patients with MDD who have a partial response

In patients with MDD experiencing partial response, REXULTI taken with antidepressants amplified antidepressant symptom response

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Antidepressants + REXULTI

MDD study design summary

REXULTI was studied in two 6-week, double-blind, placebo-controlled, fixed-dose pivotal trials of adult patients meeting DSM-IV-TR criteria for MDD. After a screening phase of 1-4 weeks, patients who met inclusion criteria were treated with an SSRI or SNRI for 8 weeks. Patients who met criteria for persistent partial responsea to an 8-week prospective treatment with an antidepressant were randomized to receive adjunctive REXULTI. Approximately 49% of patients in the 2 trials had symptoms of anxiety at randomization.1-3,b

See full study design below.

Primary endpoint was the mean change from baseline to Week 6 in the MÅDRS total score in the randomization phase1,2

aPersistent partial response criteria (prospective phase) included: <50% reduction in HAM-D17 Total Score and ≥14 HAM-D17 score at Week 8; <50% reduction in MÅDRS Total Score and Clinical Global Impression-Improvement Score of ≥3 at each scheduled visit.1,2
bPresence of anxiety symptoms was defined by a HAM-D anxiety/somatization factor of ≥7.4

DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision); HAM-D17, 17-item Hamilton Depression Rating Scale; MÅDRS, Montgomery-Åsberg Depression Rating Scale.

 

REXULTI added to an antidepressant achieved a 62% greater reduction in Montgomery-Åsberg Depression Rating Scale (MÅDRS) total score vs antidepressants alone (+ placebo)

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an=379 patients with confirmed partial response to ADT + single-blind placebo. Persistent partial response criteria (prospective phase) included: <50% reduction in HAM-D17 Total Score and ≥14 HAM-D17 score at Week 8; <50% reduction in MÅDRS Total Score and Clinical Global Impression-Improvement Score of ≥3 at each scheduled visit.1,2

*p<0.05, **p<0.01, <0.001 vs placebo. MÅDRS before prospective treatment (SD): 31.0 (4.7).5 MÅDRS after prospective treatment (SD): 27.1 (5.7).5 MÅDRS at randomization (SD): ADT + placebo (n=178), 27.3 (5.6); ADT + REXULTI 2 mg/day (n=175), 26.9 (5.7).

MEAN CHANGE FROM BASELINE ACROSS TWO PIVOTAL TRIALS

At the 2-mg/day recommended dose, the mean change from baseline (SE) at 6 weeks (randomized phase) was -8.4 (0.6) for ADT + REXULTI vs -5.2 (0.6) for ADT + placebo (-3.2 [95% CI: -4.9, -1.5], p=0.0002).1,b At the 3-mg/day maximum dose, the mean change from baseline (SE) at 6 weeks (randomized phase) was -8.3 (0.5) for ADT + REXULTI vs -6.3 (0.5) for ADT + placebo (-2.0 [95% CI: -3.4, -0.5], p=0.0079).2 At the 3-mg dose, the MÅDRS baseline (SD) for ADT + REXULTI (n=213) and ADT + placebo (n=203) was 26.5 (5.3) and 26.5 (5.2), respectively.2

aDose statistically significantly superior to placebo.
ADT, antidepressant treatment; CI, confidence interval; SD, standard deviation; SE, standard error.
The efficacy and safety of REXULTI was also studied in patients randomized to receive 1 mg/day in Study 2 (n=211). Results for the ADT + REXULTI 1 mg group for the primary efficacy parameter were not statistically significant when compared with ADT + placebo; p=0.0737.2

Contraindication:

In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.

 

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  • Titration—all patients randomized to REXULTI initiated treatment at 0.5 mg/day during Week 1. At Week 2, the REXULTI dose was increased to 1 mg/day and either maintained at 1 mg/day or increased to 2 mg/day or 3 mg/day, based on treatment assignment, from Week 3 onward
  • Primary endpoint—change from baseline to Week 6 in MÅDRS in the randomization phase1,2

aPersistent inadequate response criteria (prospective phase) included: <50% reduction in HAM-D17 Total Score and ≥14 HAM-D17 score at Week 8; <50% reduction in MÅDRS Total Score and Clinical Global Impression-Improvement Score of ≥3 at each scheduled visit.1,2

bThe efficacy and safety of REXULTI 1 mg/day were also studied in Study 2 (n=211).

cn values represent efficacy population per final protocol1,2.

dPresence of anxiety symptoms was defined by HAM-D anxiety/somatization factor of ≥74

ATRQ: Antidepressant Treat Response Questionnaire; CR: controlled release; DR: delayed release; HAM-D17: 17-item Hamilton Depression Rating Scale; SNRI: serotonin and norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; XR: extended release.

Continue exploring REXULTI

Safety Profile

See safety profile demonstrated across 2 clinical trials.

Dosing Information

Learn about once-daily treatment with a target dose of 2 mg.

INDICATIONS and IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole)

INDICATIONS

REXULTI is indicated for:

  • Use as an adjunctive therapy to antidepressants in adults with major depressive disorder
  • Treatment of schizophrenia in adults

IMPORTANT SAFETY INFORMATION

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increase the risk of suicidal thoughts and behaviors in patients aged 24 years and younger. Monitor for clinical worsening and emergence of suicidal thoughts and behaviors. The safety and effectiveness of REXULTI have not been established in pediatric patients.

Contraindication: In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: In clinical trials, elderly patients with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs including REXULTI. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of REXULTI, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation of treatment. For chronic treatment, use the lowest dose and shortest duration of REXULTI needed to produce a clinical response. If signs and symptoms of TD appear, drug discontinuation should be considered.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment.
  • Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.
  • Weight Gain: Weight gain has been observed in patients treated with REXULTI. Monitor weight at baseline and frequently thereafter.

Pathological Gambling and Other Compulsive Behaviors: Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking REXULTI. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping REXULTI if such urges develop.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia and neutropenia have been reported with antipsychotics. Agranulocytosis (including fatal cases) has been reported with other agents in this class. 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 REXULTI 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. Generally, the risk is greatest during initial dose titration and when increasing the dose. Monitor in patients vulnerable to hypotension, and those with cardiovascular and cerebrovascular diseases.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Seizures: REXULTI may cause seizures and should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Body Temperature Dysregulation: Use REXULTI with caution in patients who may experience conditions that increase body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics, including REXULTI, and should be used with caution in patients at risk for aspiration.

Potential for Cognitive and Motor Impairment: REXULTI has the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are reasonably certain REXULTI does not affect them adversely.

Concomitant Medication: Dosage adjustments are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers.

Most commonly observed adverse reactions: In clinical trials, the most common adverse reactions were:

  • Major Depressive Disorder (MDD) (adjunctive treatment to antidepressant therapy; ≥5% incidence and at least twice the rate of placebo for REXULTI vs. placebo): akathisia and weight increase
  • Schizophrenia (≥4% incidence and at least twice the rate of placebo for REXULTI vs. placebo): weight increased

Dystonia: Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy: Adequate and well-controlled studies to assess the risks of REXULTI during pregnancy have not been conducted. REXULTI should be used during pregnancy only if the benefit justifies the risk to the fetus.

Lactation: It is not known if REXULTI is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

References:

  1. Thase ME, Youakim JM, Skuban A, et al. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants. J Clin Psychiatry 2015;76(9):1224-1231.
  2. Thase ME, Youakim JM, Skuban A, et al. Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study. J Clin Psychiatry. 2015;76(9):1232-1240.
  3. Data on file (REX-291).
  4. Kostic D, Weiller E, Zhang P, et al. Adjunctive brexpiprazole (OPC-34712) in patients with MDD and anxiety symptoms: results from post-hoc analyses of two pivotal studies. Poster presented at: 54th Annual Meeting of the American College of Neuropsychopharmacology; December 6-10, 2015; Hollywood, FL.
  5. Data on file (REX-284).
  6. Data on file (REX-014).
  7. Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.

REXULTI® (brexpiprazole) Savings and Support

Help your eligible patients start saving today with the NEW Savings Card, now with TWO separate benefits!

Interested in ordering REXULTI samples? Click here

For access and copay support, go to www.otsukapatientsupport.com/rexulti or call Otsuka Patient Support at 1-855-242-7787.

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

June 202011US20EBP0111

REXULTI® (brexpiprazole) Savings and Support

Help your eligible patients start saving today with the NEW Savings Card, now with TWO separate benefits!

Interested in ordering REXULTI samples? Click here

For access and copay support, go to www.otsukapatientsupport.com/rexulti or call Otsuka Patient Support at 1-855-242-7787.

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

June 202011US20EBP0111

IMPORTANT SAFETY INFORMATION and INDICATIONS for REXULTI® (brexpiprazole)
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IMPORTANT SAFETY INFORMATION

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increase the risk of suicidal thoughts and behaviors in patients aged 24 years and younger. Monitor for clinical worsening and emergence of suicidal thoughts and behaviors. The safety and effectiveness of REXULTI have not been established in pediatric patients.

Contraindication: In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: In clinical trials, elderly patients with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs including REXULTI. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of REXULTI, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation of treatment. For chronic treatment, use the lowest dose and shortest duration of REXULTI needed to produce a clinical response. If signs and symptoms of TD appear, drug discontinuation should be considered.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment.
  • Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.
  • Weight Gain: Weight gain has been observed in patients treated with REXULTI. Monitor weight at baseline and frequently thereafter.

Pathological Gambling and Other Compulsive Behaviors: Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking REXULTI. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping REXULTI if such urges develop.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia and neutropenia have been reported with antipsychotics. Agranulocytosis (including fatal cases) has been reported with other agents in this class. 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 REXULTI 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. Generally, the risk is greatest during initial dose titration and when increasing the dose. Monitor in patients vulnerable to hypotension, and those with cardiovascular and cerebrovascular diseases.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Seizures: REXULTI may cause seizures and should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Body Temperature Dysregulation: Use REXULTI with caution in patients who may experience conditions that increase body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics, including REXULTI, and should be used with caution in patients at risk for aspiration.

Potential for Cognitive and Motor Impairment: REXULTI has the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are reasonably certain REXULTI does not affect them adversely.

Concomitant Medication: Dosage adjustments are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers.

Most commonly observed adverse reactions: In clinical trials, the most common adverse reactions were:

  • Major Depressive Disorder (MDD) (adjunctive treatment to antidepressant therapy; ≥5% incidence and at least twice the rate of placebo for REXULTI vs. placebo): akathisia and weight increase
  • Schizophrenia (≥4% incidence and at least twice the rate of placebo for REXULTI vs. placebo): weight increased

Dystonia: Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy: Adequate and well-controlled studies to assess the risks of REXULTI during pregnancy have not been conducted. REXULTI should be used during pregnancy only if the benefit justifies the risk to the fetus.

Lactation: It is not known if REXULTI is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

INDICATIONS

REXULTI is indicated for:

  • Use as an adjunctive therapy to antidepressants in adults with major depressive disorder
  • Treatment of schizophrenia in adults

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.