This website is intended for use by
U.S. healthcare professionals only.

Partial Response to Antidepressant Monotherapies in Patients with Major Depressive Disorder (MDD)

Partial Response to Antidepressant Monotherapies in Patients with Major Depressive Disorder (MDD)

Video: Dr. Jain on Major Depressive Disorder Treatment Considerations

At least half of patients with MDD have an partial response to antidepressant medications.1,a In the video below, Dr. Jain discusses treatment considerations that may address the partial response of MDD patients.

Dr. Rakesh Jain, MD, MPH

Clinical Professor, Department of Psychiatry and Behavior Sciences, Texas Tech University School of Medicine

Dr. Jain is a paid consultant of Otsuka America Pharmaceutical, Inc. and Lundbeck.

“I’m on an antidepressant, but I still have little interest or desire in doing things.”
“My depression is not getting better.”
“I am on a treatment for depression, but I am still feeling sad.”

Dr. Jain: Do you see patients like these in your practice?

Dr. Jain: Major depressive disorder, or MDD, can be overwhelming for your patients and challenging for clinicians—especially when our patients continue to experience symptoms.

Dr. Jain: My name is Dr. Rakesh Jain, and I am a Clinical Professor in the Department of Psychiatry and Behavioral Sciences at Texas Tech University School of Medicine.

This video was created by Otsuka America Pharmaceutical, Inc. and Lundbeck for healthcare professionals looking for guidance when patients with MDD have symptoms that are not adequately treated with antidepressant medications.

We’ll review the prevalence of inadequate response to antidepressant therapy in patients with MDD. We will discuss recommended treatment options, and explore current utilization of atypical antipsychotics as adjunctive treatment for these patients.

Many of us have had patients with MDD who don’t respond well to an initial course of antidepressant treatment, but how common is this problem?

The STAR*D trial evaluated outcomes in patients with MDD across successive steps of treatment.

Dr. Jain in voiceover: In this large study involving a broadly representative population of outpatients, at least 50% of patients with MDD did not achieve an adequate response after initial treatment with an SSRI.

Results of that classic study, published more than 10 years ago, have been confirmed in several meta-analyses. Together, these studies demonstrate that there is no one-size-fits-all approach for MDD.

Dr. Jain in voiceover: If we extrapolate from the STAR*D study to the overall US population, we can estimate that as many as 8.2 million adults in the United States may currently have an inadequate response to their antidepressant.

So, given that estimated prevalence, odds are that you may have patients with MDD in your practice who demonstrate inadequate response as well.

Dr. Jain in voiceover: What is the best approach to treat patients with MDD experiencing an inadequate treatment response? Let’s look at the professional guidelines.

The American Psychiatric Association, the leading authority for MDD treatment guidelines, endorses four treatment options, which may be used concurrently: First, optimize medication dose as tolerated. Second, augment pharmacologic therapy with depression-focused psychotherapy, an option at any time during treatment. Third, switch to a different monotherapy of the same or different pharmacologic class, and fourth, augment with antidepressant pharmacotherapy, including an atypical antipsychotic.

Dr. Jain: At least two meta-analyses were recently published comparing outcomes in patients with MDD who had an inadequate response and who were then treated with an antidepressant alone or an antidepressant plus an atypical antipsychotic.

Both showed adjunctive use of atypical antipsychotics significantly increased response rates versus antidepressant alone. This provides further support for considering an atypical antipsychotic when adjunctive therapy is indicated.

Dr. Jain in voiceover: However, although we see that patients can potentially benefit from adjunctive treatment, one study suggested that fewer than 10% of patients with MDD who received a change in their treatment received an atypical antipsychotic. What could be the reasons for this discrepancy?

Dr. Jain: Let’s look at a survey that asked for reasons why physicians did or did not prescribe an atypical antipsychotic for their patients with MDD who had an inadequate response to treatment.

In a recent survey, physicians in the United States and Europe were asked to document the reasons behind their treatment decisions for 10 consecutive adults with MDD who had an inadequate response to antidepressant therapy for whom they had considered or made a treatment change.

The most common reason for not prescribing an adjunctive atypical antipsychotic, or not prescribing one earlier, was a preference to wait to see if symptoms improved. Other common reasons were that the patient’s response to antidepressant therapy was adequate, their symptoms were not severe enough for an atypical antipsychotic, and the physician had concerns about tolerability or safety.

The most common reasons physicians reported that they did prescribe an adjunctive atypical antipsychotic for individuals with MDD with an inadequate response to their antidepressant were: that they were looking for efficacy and symptom control in addition to the patient's current treatment, specific drug features, as well as the patient's disease and their treatment response history.

Dr. Jain in voiceover: What is your approach when your patients face an inadequate response to antidepressant treatment?

Dr. Jain: It is my sincere hope that you consider this information when you’re developing treatment strategies that may improve symptoms for your patients with MDD for whom monotherapy is not enough.

Thank you.


Partial response unmet need

aAs 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.1
SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; STAR*D, Sequenced Treatment Alternatives to Relieve Depression

bIn 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.2
HAM-D17, 17-item Hamilton Depression Rating Scale; MÅDRS, Montgomery-Åsberg Depression Rating Scale.


Continue exploring REXULTI

Efficacy Data

Review efficacy results from pivotal clinical trials for REXULTI.

Safety Profile

See safety profile for REXULTI, demonstrated across 2 clinical trials.

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. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163:1905-1917.
  2. Wen XJ, Wang LM, Liu ZL, Huang A, Liu YY, Hu JY. Meta-analysis on the efficacy and tolerability of the augmentation of antidepressants with atypical antipsychotics in patients with major depressive disorder. Braz J Med Biol Res. 2014;47(7):605-616.
  3. McIntyre RS, Weiller E. Real-world determinants of adjunctive antipsychotic prescribing for patients with major depressive disorder and inadequate response to antidepressants: a case study review. Adv Ther. 2015;32(5):429-444.

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)
See More
Minimize

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.