Duloxetine vs Escitalopram for Depression

(AtLAS-A Trial)

Overseen By Heidi K Schroeder, BS

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Cincinnati

Must not be taking: Antidepressants

Disqualifiers: Intellectual disability, Suicide risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram, followed by open-label naturalistic follow-up.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those taking medications that require a taper or washout period of more than 5 days. It's best to discuss your current medications with the trial team.

Is it safe to use Duloxetine and Escitalopram for depression?

Studies show that both Duloxetine and Escitalopram are generally safe for treating depression, with some patients experiencing mild to moderate side effects. Escitalopram is noted for having fewer adverse events compared to some other antidepressants. ^{1 2 3 4 5}

How do Duloxetine and Escitalopram differ from other drugs for depression?

Duloxetine and Escitalopram are unique because they target different neurotransmitters in the brain to treat depression. Duloxetine affects both serotonin and norepinephrine, while Escitalopram primarily targets serotonin, offering different options for patients based on their specific needs and responses to treatment. ^{6 7 8 9 10}

Research Team

Jeffrey R Strawn, MD, FAACAP

Principal Investigator

University of Cincinnati

Eligibility Criteria

The AtLAS-A trial is for English-speaking adolescents aged 12-17 with anxiety disorders as per DSM-5 criteria. They must have a caregiver to monitor safety and manage medication, no significant physical health issues, and agree to use reliable contraception if sexually active. Excluded are those with intellectual disabilities, recent suicide risk, allergies or non-response to the study drugs, certain medication regimens or psychotherapy changes within the last month.

Inclusion Criteria

No clinically significant abnormalities on physical examination

I use skin patches or injections for birth control.

You must use both a diaphragm and a condom for contraception.

Exclusion Criteria

Suicide risk as determined by either: (1) any suicide attempt within the past 6 months and/or (2) significant risk at Visit 1 (Screening) or Visit 2 (Baseline), as judged by the Investigator

My mental health treatment has been stable for at least a month.

I have a serious health condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram

8 weeks

Weekly visits for dose adjustments

Follow-up

Open-label naturalistic follow-up to monitor long-term response and relapse

16 weeks

Monthly visits

Treatment Details

Interventions

• Duloxetine
• Escitalopram

Trial Overview This study tests two antidepressants: Duloxetine and Escitalopram in teens with anxiety. It starts with a double-blind phase where neither participants nor researchers know who's getting which drug. After that comes an open-label follow-up without this blinding.

Participant Groups

Group I: Duloxetine Active Control 1 Intervention

Patients randomized to duloxetine, treatment will be initiated at 30 mg qAM through Week 4 (V5) (consistent with the registration trial for duloxetine in pediatric patients with generalized anxiety disorder). Then, duloxetine will be increased to 60 mg qAM at Week 4 (V5) and will be continued at this dose until Week 6 (V6) or the end of the acute phase of the study. Beginning at Week 6 (V6), duloxetine may be increased to 90 mg daily and at Week 8 (V7), may be increased to 120 mg daily.

Group II: Escitalopram Active Control 1 Intervention

Patients randomized to escitalopram, will initiate treatment at 5 mg qAM for 1 week and then 10 mg qAM (the recommended starting dose for adolescents 12-17 years and the dose used in the pediatric registration trials). After Week 4 (V5), escitalopram will be increased to 15 mg and this dose will be continued until either Week 6 (V6) or the end of the acute phase of the study; however, at Week 6 (V6), escitalopram may be increased to 20 mg qAM based on efficacy.

Duloxetine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Approved in European Union as Cymbalta / Yentreve for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Diabetic Peripheral Neuropathic Pain
• Fibromyalgia
• Stress Urinary Incontinence

Approved in Canada as Cymbalta for:

• Major Depressive Disorder
• Generalized Anxiety Disorder
• Fibromyalgia
• Neuropathic Pain
• Chronic Musculoskeletal Pain

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Findings from Research

In a study of 929 patients with major depressive disorder, escitalopram was found to be more effective than SNRIs (duloxetine and venlafaxine XR) in achieving remission without adverse events, with 28.4% of escitalopram patients reaching this outcome compared to 21.6% for SNRIs.

Patients treated with escitalopram had significantly higher odds of achieving remission free from any adverse events (38% greater), moderate-to-severe adverse events (28% greater), and study drug-related adverse events (34% greater), highlighting its favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of major depressive disorder without adverse events: a comparison of escitalopram versus serotonin norepinephrine reuptake inhibitors. Signorovitch, J., Ramakrishnan, K., Ben-Hamadi, R., et al.[2015]

A study evaluated the adherence to prescribing guidelines for citalopram and found that implementing an EMIS safety prompt and providing prescriber training led to a significant reduction in incorrect prescriptions for patients over 65, from 8 to 1.

The interventions also decreased dangerous drug interactions involving citalopram from 44 to 8 and overall unsafe prescribing from 47 to 9, highlighting improved patient safety and resource use that could be applied to other medications with safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safer citalopram use in primary care: Can staff education and prescribing prompts improve adherence to national guidance? A closed loop clinical audit, service evaluation and quality improvement study. Waller, M.[2023]

In an 8-week study involving 278 patients with major depressive disorder, escitalopram was found to be more effective than duloxetine, showing a greater improvement in depression scores as measured by the MADRS scale.

Escitalopram also had a better safety profile, with significantly fewer patients discontinuing treatment due to adverse events compared to those taking duloxetine (2% vs 13%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind comparison of escitalopram and duloxetine in the acute treatment of major depressive disorder. Khan, A., Bose, A., Alexopoulos, GS., et al.[2022]

In a double-blind trial with 60 patients suffering from endogenous depression, citalopram showed a significantly greater reduction in depression scores compared to mianserin after just 1 and 2 weeks of treatment.

Citalopram was found to be safe, with only mild to moderate side effects reported in six patients, while no cardiovascular side effects were observed, suggesting it may be a preferable option over mianserin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citalopram versus mianserin. A controlled, double-blind trial in depressed patients. de Wilde, J., Mertens, C., Overø, KF., et al.[2019]

In a study involving 217 patients with depression, citalopram and fluvoxamine were found to be equally effective in treating depressive disorders.

Citalopram was better tolerated than fluvoxamine, causing fewer gastrointestinal side effects, although this difference did not impact the overall drop-out rates from the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group. Haffmans, PM., Timmerman, L., Hoogduin, CA.[2022]

The CILON-T trial, involving 960 patients, aims to determine if adding cilostazol to standard dual anti-platelet therapy (aspirin and clopidogrel) can reduce major cardiovascular events and platelet reactivity after drug-eluting stent implantation.

This study will also explore the potential interaction between lipophilic statins (like atorvastatin) and clopidogrel, providing insights into their combined effects on patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design and rationale of 'Influence of Cilostazol-based triple anti-platelet therapy on ischemic complication after drug-eluting stent implantation (CILON-T)' study: A multicenter randomized trial evaluating the efficacy of Cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease. Lee, SP., Suh, JW., Park, KW., et al.[2021]

In a study of 15,968 chronic ischemic stroke patients, cilostazol and clopidogrel showed no significant differences in efficacy or safety over a 3-year period, with similar rates of recurrent strokes and major bleeding events.

However, cilostazol may offer advantages for patients with a history of hypertension or gastrointestinal bleeding, showing trends towards lower rates of recurrent ischemic strokes and major bleeding compared to clopidogrel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of long-term efficacy and safety between cilostazol and clopidogrel in chronic ischemic stroke: a nationwide cohort study. Lee, TH., Lin, YS., Liou, CW., et al.[2022]

Cilostazol, whether used alone or in combination with aspirin or clopidogrel, significantly reduces the risk of recurrent and ischemic strokes compared to standard single antiplatelet therapy (SAPT), based on a systematic review of 10 studies involving over 7,800 participants.

Cilostazol monotherapy is particularly effective in lowering the risk of hemorrhagic stroke without increasing its incidence, making it a safer option than SAPT, while combination therapy shows superior efficacy for overall stroke prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilostazol Mono and Combination Treatments in Ischemic Stroke: An Updated Systematic Review and Meta-Analysis. Kim, SM., Jung, JM., Kim, BJ., et al.[2020]

Novel antiplatelet agents prasugrel and ticagrelor offer faster and more consistent inhibition of platelet aggregation compared to clopidogrel, leading to better clinical outcomes for patients with acute coronary syndromes.

While these newer agents improve survival and reduce ischemic complications, they also carry a higher risk of bleeding, highlighting the need for careful consideration of safety versus efficacy in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which antiplatelet agent for whom? Which patient populations benefit most from novel antiplatelet agents (ticagrelor, prasugrel)? Varenhorst, C., James, S.[2021]

In a study of 4,754 patients, cilostazol showed similar effectiveness and safety compared to clopidogrel for preventing recurrent ischemic strokes, with no significant differences in major outcomes like recurrent strokes or gastrointestinal bleeding.

However, cilostazol may be more effective than clopidogrel in hypertensive patients, showing a lower incidence of recurrent ischemic strokes (2.5% vs 3.9%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of cilostazol versus clopidogrel in secondary prevention of noncardioembolic ischemic stroke. Lee, YJ., Je, NK.[2023]

References

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

Remission of major depressive disorder without adverse events: a comparison of escitalopram versus serotonin norepinephrine reuptake inhibitors. [2015]

2. India pubmed.ncbi.nlm.nih.gov

Safer citalopram use in primary care: Can staff education and prescribing prompts improve adherence to national guidance? A closed loop clinical audit, service evaluation and quality improvement study. [2023]

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

Double-blind comparison of escitalopram and duloxetine in the acute treatment of major depressive disorder. [2022]

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

Citalopram versus mianserin. A controlled, double-blind trial in depressed patients. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Study design and rationale of 'Influence of Cilostazol-based triple anti-platelet therapy on ischemic complication after drug-eluting stent implantation (CILON-T)' study: A multicenter randomized trial evaluating the efficacy of Cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease. [2021]

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

Comparison of long-term efficacy and safety between cilostazol and clopidogrel in chronic ischemic stroke: a nationwide cohort study. [2022]

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

Cilostazol Mono and Combination Treatments in Ischemic Stroke: An Updated Systematic Review and Meta-Analysis. [2020]

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

Which antiplatelet agent for whom? Which patient populations benefit most from novel antiplatelet agents (ticagrelor, prasugrel)? [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of cilostazol versus clopidogrel in secondary prevention of noncardioembolic ischemic stroke. [2023]