Is Partial Response Good Enough?
Patient Profiles

Is partial response good enough?

Major depression among adults in the US has continued to increase1

11 million
11 million

Of an estimated 22 million US adults affected, approximately half, or 11 million, may not fully respond to their antidepressant2,3,a

Partial Response
Partial Response

has been defined as a 25-50% reduction from baseline in depression scale scores4,b

MDD symptoms reported by adult patients on one or more antidepressant5

frequently reported symptoms frequently reported symptoms
frequently reported symptoms frequently reported symptoms

Despite evidence supporting appropriate use, a chart review study showed that a patient may undergo ~5 treatment changes before being prescribed an adjunctive atypical antipsychotic6

Decrease in response rate icon
Decrease in response rate icon

Antidepressant treatment changes may affect response rates. In the STAR*D study, rates of response decreased with each additional switch in antidepressant treatment (48.6% in Step 1 to 16.3% in Step 4)2,d

Atypical antipsychotics may increase response rates for patients

Meta-analysis 68% greater chance of a response Meta-analysis 68% greater chance of a response
Meta-analysis 68% greater chance of a response Meta-analysis 68% greater chance of a response

According to a meta-analysis,

The chance of response doubled in patients treated with adjunctive atypical antipsychotics vs antidepressant treatments alone (odds ratio=1.68)7,e

aDemonstrated in almost 3700 adult patients with MDD who were prescribed an SSRI. In the STAR*D study, inadequate response was defined as less than 50% reduction from treatment step entry in QIDS-SR16 score at 12 to 14 weeks. Statistic is an extrapolation of the STAR*D study.2

bThe HAM-D has been the metric of choice for measuring depression in research settings. Other scales such as the MÅDRS and the Inventory for Depressive Symptomatology have also been used.4

cBased on an online survey of adult patients (n=2096) age 18-65 with an inadequate response to an antidepressant who reported symptoms occurring (1) several days to (3) nearly every day on the PHQ-9; current symptoms of depression were assessed with a modified PHQ-9 that excluded the question of suicidal ideation; non-PHQ-9 symptoms were elicited from a checklist of clinical symptoms associated with depression. In the survey, 38% of participants were taking combination antidepressant therapy (more than one antidepressant at the same time) and 16% were taking adjunctive atypical antipsychotics.5

dAs demonstrated in almost 3700 adult patients with MDD who were prescribed antidepressants. In the STAR*D study, partial response was defined as a less-than-50% reduction from treatment step entry in Quick Inventory of Depressive Symptomatology Self-Report score at 12-14 weeks. The patient sample received successive acute treatment steps: 3671 patients entered at Step 1; 1439 patients continued at Step 2; 390 patients proceeded to Step 3; 123 patients advanced through all 4 steps. After SSRI monotherapy in Step 1, treatment options included switching medications or augmentation with either medication or cognitive therapy. Adjunctive atypical antipsychotics were not included at any step. Patients who either did not achieve response with a treatment or were unable to tolerate a treatment were encouraged to move to the next step.2

eIn a meta-analysis, response was defined as a 50% improvement from baseline to endpoint on either the MÅDRS or HAM-D17. Meta-analysis included 17 randomized trials with 3807 patients (duration range: 4-12 weeks) comparing adjunctive antipsychotic treatment to SSRI/SNRI treatment in adult patients (age range: 18-65 years) with MDD. There was a 68% greater chance of response from the antidepressant + adjunctive antipsychotic group vs the antidepressant + placebo group.7

HAM-D17, 17-item Hamilton Depression Rating Scale; MÅDRS, Montgomery-Åsberg Depression Rating Scale; MDD, major depressive disorder; PHQ-9, Patient Health Questionnaire-9; QIDS-SR16, Quick Inventory of Depressive Symptomatology-Self Report 16; SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; STAR*D, Sequenced Treatment Alternatives to Relieve Depression.

See what partial response looks like in a patient like Kimberly
 

Watch Dr. Jain discuss the prevalence of partial response
in MDD and considerations for addressing it

Dr. Jain discussing the prevalence of partial response in MDD and considerations for addressing it.

Rakesh Jain, MD, MPH

Clinical Professor

Department of Psychiatry

Texas Tech University School of Medicine

Austin, Texas

The presenter is a paid consultant of Otsuka America Pharmaceutical, Inc. and Lundbeck.

ADDING AN ATYPICAL ANTIPSYCHOTIC IN MDD: WHY NOT EARLIER?

Review treatment history data for patients with MDD experiencing partial response to antidepressants, and learn about REXULTI as an adjunctive treatment option.

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Clinical trial results of REXULTI for Major Depressive Disorder.

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Full Prescribing Information

All rights reserved.

October 2024
11US24EBP0400
ISI Block Title

INDICATIONS and IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole)

INDICATIONS

REXULTI is indicated for:

  • Use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults
  • Treatment of schizophrenia in adults and pediatric patients ages 13 years and older
  • Treatment of agitation associated with dementia due to Alzheimer’s disease

Limitations of Use: REXULTI is not indicated as an as needed (“prn”) treatment for agitation associated with dementia due to Alzheimer’s disease.

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 without agitation associated with dementia due to Alzheimer’s disease.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients and young adult patients. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. The safety and effectiveness of REXULTI have not been established in pediatric patients with MDD.

Contraindication: In patients with known hypersensitivity 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 without agitation associated with dementia due to Alzheimer’s disease.

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 (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). 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, appear to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after relatively brief treatment periods, 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, including REXULTI, have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia and diabetes mellitus, in some cases extreme and associated with diabetic ketoacidosis, hyperosmolar coma, or death, have 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 patients with severe neutropenia.

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, and 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 treatment.

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 (eg, 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 may cause somnolence and has the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including operating motor vehicles, 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 of adults, 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): weight increased, somnolence, and akathisia.
  • Schizophrenia (≥4% incidence and at least twice the rate of placebo for REXULTI vs placebo): weight increased. Adverse reactions in patients 13 to 17 years of age were generally similar to those observed in adult patients.
  • Agitation associated with dementia due to Alzheimer’s disease (≥4% incidence and at least twice the rate of placebo for REXULTI vs placebo): nasopharyngitis and dizziness.

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.

IMPORTANT SAFETY INFORMATION
and INDICATIONS

 
  • Use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults
  • Treatment of schizophrenia in adults and pediatric patients ages 13 years and older
  • Treatment of agitation associated with Alzheimer’s dementia (AAD)
ISI Block Title

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 without agitation associated with dementia due to Alzheimer’s disease.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients and young adult patients. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. The safety and effectiveness of REXULTI have not been established in pediatric patients with MDD.

Contraindication: In patients with known hypersensitivity 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 without agitation associated with dementia due to Alzheimer’s disease.

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 (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). 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, appear to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after relatively brief treatment periods, 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, including REXULTI, have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia and diabetes mellitus, in some cases extreme and associated with diabetic ketoacidosis, hyperosmolar coma, or death, have 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 patients with severe neutropenia.

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, and 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 treatment.

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 (eg, 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 may cause somnolence and has the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including operating motor vehicles, 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 of adults, 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): weight increased, somnolence, and akathisia.
  • Schizophrenia (≥4% incidence and at least twice the rate of placebo for REXULTI vs placebo): weight increased. Adverse reactions in patients 13 to 17 years of age were generally similar to those observed in adult patients.
  • Agitation associated with dementia due to Alzheimer’s disease (≥4% incidence and at least twice the rate of placebo for REXULTI vs placebo): nasopharyngitis and dizziness.

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 for the treatment of major depressive disorder (MDD) in adults
  • Treatment of schizophrenia in adults and pediatric patients ages 13 years and older
  • Treatment of agitation associated with dementia due to Alzheimer’s disease

Limitations of Use: REXULTI is not indicated as an as needed (“prn”) treatment for agitation associated with dementia due to Alzheimer’s disease.

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

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