Escitalopram + Brexpiprazole for Depression

(CAN-BIND-17 Trial)

Recruiting at 6 trial locations

Overseen By Roumen Milev, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University Health Network, Toronto

Must not be taking: Antidepressants, Psychotropics

Disqualifiers: Bipolar, Substance abuse, Neurological disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

400 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study that will test a predictive biomarker algorithm based on results from a previous study. The goal of this study is to integrate clinical, imaging, EEG, and molecular data across 8 sites to predict treatment outcome for patients experiencing a major depressive episode (MDE).

Will I have to stop taking my current medications?

Yes, you will need to stop taking psychotropic medications (drugs that affect your mood, thoughts, or behavior) for at least 5 half-lives before the study starts, which is about 1 week for most antidepressants and 5 weeks for fluoxetine. However, you can continue using stable doses of sleep aids or ADHD medications.

What data supports the effectiveness of the drug combination of Escitalopram and Brexpiprazole for depression?

Research shows that Brexpiprazole, when used alongside other antidepressants, can help improve symptoms in people with major depressive disorder who haven't fully responded to previous treatments. This suggests that combining Brexpiprazole with Escitalopram might be effective for treating depression. ^{1 2 3 4 5}

Is the combination of Escitalopram and Brexpiprazole safe for humans?

Escitalopram is generally considered safe for treating depression, but there are concerns about heart-related side effects, especially in cases of overdose or in patients with certain heart conditions. It's important to monitor heart health, particularly in older adults or those with a history of heart issues. ^{6 7 8 9 10}

How is the drug combination of Escitalopram and Brexpiprazole unique for treating depression?

The combination of Escitalopram and Brexpiprazole is unique because it combines an antidepressant (Escitalopram) with an antipsychotic (Brexpiprazole), potentially offering a more comprehensive approach to treating depression by targeting different brain pathways compared to standard treatments that typically use only one type of medication. ^{11 12 13 14 15}

Research Team

Rudolf Uher, MD

Principal Investigator

Nova Scotia Health Authority

Eligibility Criteria

The OPTIMUM-D trial is for adults aged 18-60 with major depressive disorder (MDD) and a current major depressive episode (MDE). Participants must have a moderate to severe depression score, no significant mental or physical health issues, not be on psychotropic meds recently, speak English fluently, and have had the episode for at least 3 months. Excluded are those with bipolar disorder, unstable conditions, pregnancy/breastfeeding women, multiple failed depression treatments, recent psychotherapy starters or intolerance to study drugs.

Inclusion Criteria

I am between 18 and 60 years old.

I am between 18 and 60 years old.

I haven't taken any psychiatric medication for the required time before my first visit.

Exclusion Criteria

I began psychological treatment in the last 3 months and plan to continue.

I have tried 4 or more different depression medications without success.

I had issues with escitalopram or brexpiprazole, or antidepressants caused me to become overly energetic.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Primary Treatment

Participants receive open-label escitalopram and either blinded placebo or brexpiprazole based on group assignment for 8 weeks

8 weeks

4 visits (in-person)

Secondary Extension

Participants continue treatment with open-label escitalopram and either open-label brexpiprazole or no additional medication based on response for 4 weeks

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Brexpiprazole
• Escitalopram

Trial Overview This trial tests whether data from clinical assessments, brain scans (imaging), EEGs (brain wave tests), and molecular studies can predict how well patients will respond to two antidepressants: Escitalopram or Brexpiprazole. It's conducted across eight sites using an algorithm developed from previous research.

Participant Groups

Group I: Random Allocation; Escitalopram + Brexpiprazole Active Control 2 Interventions

Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.

Group II: Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole Active Control 2 Interventions

Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted as non-responders to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.

Group III: Allocation by Predictive Biomarker Algorithm; Placebo Placebo Group 1 Intervention

Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted to respond to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.

Group IV: Random Allocation; Placebo Placebo Group 1 Intervention

Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.

Brexpiprazole is already approved in United States, Canada, European Union, Japan, Brazil for the following indications:

Approved in United States as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)
• Schizophrenia
• Agitation associated with dementia due to Alzheimer's disease

Approved in Canada as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)
• Schizophrenia

Approved in European Union as Rexulti for:

• Schizophrenia

Approved in Japan as Rexulti for:

• Schizophrenia

Approved in Brazil as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Nova Scotia Health Authority

Lead Sponsor

Trials

302

Recruited

95,300+

Queen's University

Collaborator

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Baycrest

Collaborator

Trials

46

Recruited

6,900+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Simon Fraser University

Collaborator

Trials

59

Recruited

12,500+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

McGill University

Collaborator

Trials

421

Recruited

1,017,000+

Findings from Research

Brexpiprazole, a new treatment for schizophrenia, has been shown to be more effective than a placebo in reducing symptoms, with significant improvements observed at doses of 1 mg, 2 mg, and 4 mg over 6 weeks in 12 clinical trials.

The safety and tolerability of Brexpiprazole are favorable, with side effects like akathisia, headache, and insomnia occurring at rates similar to those seen with placebo, indicating it is a well-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole for the treatment of schizophrenia. Yee, A.[2018]

Brexpiprazole, at doses of 2-3 mg/day, significantly improved depression symptoms in adults with major depressive disorder who did not respond adequately to previous antidepressant treatments, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).

The treatment was generally well tolerated, with common side effects including akathisia, somnolence, and headache, but no unexpected adverse effects were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study. Hobart, M., Skuban, A., Zhang, P., et al.[2019]

Brexpiprazole, a serotonin-dopamine activity modulator, has been shown to be more effective than standard antidepressant therapy alone in improving depressive symptoms in adults with major depressive disorder who did not fully respond to previous treatments, based on two phase III trials.

The drug was generally well tolerated over treatment periods of up to 52 weeks, suggesting a lower risk of activation-like side effects compared to similar medications like aripiprazole, making it a suitable adjunctive option for patients with persistent symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive Brexpiprazole: A Review in Major Depressive Disorder. McKeage, K.[2018]

Brexpiprazole is an effective new treatment for schizophrenia when used alone, providing a novel option for patients managing this condition.

Additionally, brexpiprazole can be used as an adjunctive therapy for major depressive disorder, enhancing the effectiveness of other treatments for individuals with this mental health issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. Eaves, S., Rey, JA.[2022]

Brexpiprazole is a new drug similar to aripiprazole and is being reviewed by the FDA for treating schizophrenia and as an add-on treatment for major depressive disorder.

This drug is also being tested for other conditions like ADHD, PTSD, and agitation in Alzheimer's patients, showcasing its potential for multiple therapeutic uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexpiprazole: another multipurpose antipsychotic drug? Howland, RH.[2015]

Regulatory alerts regarding the cardiac toxicity of citalopram and escitalopram primarily concern patients with a history of syncope or poisoning, suggesting that the risk may not be as widespread as initially thought.

It is recommended that elderly patients undergo an electrocardiogram as a precaution before starting treatment with these medications to monitor for potential cardiac issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Citalopram, escitalopram and prolonged QT: warning or alarm?]. Alvarez, E., Vieira, S., Garcia-Moll, X.[2022]

Escitalopram, the S-enantiomer of citalopram, effectively inhibits serotonin reuptake, which is crucial for its antidepressant effects, with minimal interaction with other receptors, ensuring a better safety profile.

Clinical trials show that a daily dose of 10 mg of escitalopram is as effective as 40 mg of citalopram, highlighting its efficacy and tolerability, making it a refined option for treating depression and anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram: A New SSRI for the Treatment of Depression in Primary Care. Culpepper, L.[2020]

A case study of a 52-year-old man who overdosed on escitalopram revealed significant ECG abnormalities, including a prolonged QT interval and junctional rhythm, highlighting potential cardiac risks associated with escitalopram overdose.

Despite the initial severe ECG changes, the patient's heart rhythm normalized within 48 hours without specific treatment for the QT prolongation, suggesting that while escitalopram overdose can lead to serious cardiac effects, recovery is possible with appropriate medical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corrected QT interval prolongation after an overdose of escitalopram, morphine, oxycodone, zopiclone and benzodiazepines. Baranchuk, A., Simpson, CS., Methot, M., et al.[2021]

In a study involving 240 Chinese patients with major depressive disorder, escitalopram (10-20 mg/d) was found to be as effective and safe as citalopram (20-40 mg/d) over a 6-week treatment period, with no significant differences in depression scores or response rates.

Both medications had similar safety profiles, with no serious adverse events reported, indicating that escitalopram can be a suitable alternative to citalopram for treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study. Ou, JJ., Xun, GL., Wu, RR., et al.[2022]

Escitalopram, the active s-enantiomer of citalopram, is an effective selective serotonin reuptake inhibitor (SSRI) used to treat major depressive disorder.

As an SSRI, escitalopram works by increasing serotonin levels in the brain, which can help improve mood and alleviate symptoms of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram (Lexapro) for depression. Masilamani, S., Ruppelt, SC.[2022]

In a 12-week study involving 44 outpatients with binge-eating disorder (BED) and obesity, high-dose escitalopram (average 26.5 mg/day) was found to significantly reduce weight, body mass index (BMI), and overall severity of illness, although it did not effectively reduce obsessive-compulsive symptoms associated with BED.

While escitalopram showed some promise in reducing binge-eating frequency, the results were inconclusive due to limitations in statistical power, indicating that further research is needed to fully understand its efficacy in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose escitalopram in the treatment of binge-eating disorder with obesity: a placebo-controlled monotherapy trial. Guerdjikova, AI., McElroy, SL., Kotwal, R., et al.[2022]

In a small study of 10 individuals with bulimia who did not respond to traditional antidepressants, treatment with the long-acting opiate antagonist naltrexone led to a significant reduction in bulimic symptoms for 7 participants, with improvements lasting for 3 to 5 months.

These findings suggest that naltrexone could be a promising alternative treatment for bulimia, particularly for those resistant to standard therapies, and may help researchers understand the role of opioids in eating disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of antidepressant-resistant bulimia with naltrexone. Jonas, JM., Gold, MS.[2019]

In an 8-week study involving 33 obese binge eaters and 22 bulimics, naltrexone significantly reduced binge duration in bulimics by 36%, while imipramine reduced binge duration in obese bingers by 88%.

Both medications showed a reduction in binge frequency, but this effect was not significantly different from the placebo, suggesting that while naltrexone and imipramine may help with binge eating, the placebo effect is also strong in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a tricyclic antidepressant and opiate antagonist on binge-eating behavior in normoweight bulimic and obese, binge-eating subjects. Alger, SA., Schwalberg, MD., Bigaouette, JM., et al.[2018]

In a 17-week pilot study involving 27 adults with binge eating disorder (BED), liraglutide 3.0 mg/day led to a significant weight loss of 5.2% compared to 0.9% in the placebo group, indicating its potential efficacy for weight management in BED.

While both liraglutide and placebo groups experienced reductions in binge eating episodes, the difference in the number of objective binge episodes per week was not statistically significant, suggesting that while liraglutide may aid in weight loss, its effect on binge eating frequency needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot randomized controlled trial of liraglutide 3.0 mg for binge eating disorder. Allison, KC., Chao, AM., Bruzas, MB., et al.[2023]

Pharmacological treatments for bulimia nervosa (BN) have shown efficacy, with tricyclic antidepressants, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors significantly reducing binge eating and purging compared to placebo.

For binge eating disorder, several medications, including antidepressants and topiramate, have demonstrated some effectiveness, indicating potential treatment options, although further research is needed for certain promising agents like odansitron and topiramate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Academy for Eating Disorders International Conference on Eating Disorders. Denver, CO, USA, May 29-31, 2003. Kaplan, AS.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Brexpiprazole for the treatment of schizophrenia. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Adjunctive Brexpiprazole: A Review in Major Depressive Disorder. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Brexpiprazole: another multipurpose antipsychotic drug? [2015]

6. Spain pubmed.ncbi.nlm.nih.gov

[Citalopram, escitalopram and prolonged QT: warning or alarm?]. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Escitalopram: A New SSRI for the Treatment of Depression in Primary Care. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Corrected QT interval prolongation after an overdose of escitalopram, morphine, oxycodone, zopiclone and benzodiazepines. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Escitalopram (Lexapro) for depression. [2022]

11. England pubmed.ncbi.nlm.nih.gov

High-dose escitalopram in the treatment of binge-eating disorder with obesity: a placebo-controlled monotherapy trial. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Treatment of antidepressant-resistant bulimia with naltrexone. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Effect of a tricyclic antidepressant and opiate antagonist on binge-eating behavior in normoweight bulimic and obese, binge-eating subjects. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

A pilot randomized controlled trial of liraglutide 3.0 mg for binge eating disorder. [2023]

15. England pubmed.ncbi.nlm.nih.gov

Academy for Eating Disorders International Conference on Eating Disorders. Denver, CO, USA, May 29-31, 2003. [2019]