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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two medications, duloxetine and escitalopram, to evaluate their effectiveness in treating depression in young people. Researchers aim to determine which drug works better over a short period and monitor its effects over time. Teens aged 12 to 17 with depression and anxiety issues, such as frequent panic attacks or social anxiety, may be suitable candidates for this study. As a Phase 4 trial, this research seeks to understand how these FDA-approved treatments can benefit more patients.

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.

What is the safety track record for duloxetine and escitalopram?

Research has shown that duloxetine is generally well-tolerated for treating major depressive disorder. A review of studies confirms its safety, though some individuals might experience side effects like trouble sleeping or mood changes. Duloxetine's use for various conditions means its safety profile is well-established.

Studies have demonstrated that escitalopram is effective and safe for treating major depressive disorder. The FDA has approved it for adults and teens. Research highlights its favorable tolerance compared to other antidepressants, with most people experiencing manageable side effects.

Both duloxetine and escitalopram have proven safety records for treating depression. Most study participants have found them tolerable, experiencing only mild side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments, duloxetine and escitalopram, for depression because they offer distinct approaches to managing the condition. Unlike many standard antidepressants, duloxetine not only targets serotonin but also norepinephrine, potentially providing a broader spectrum of relief for depressive symptoms. Escitalopram, on the other hand, is a selective serotonin reuptake inhibitor (SSRI) known for its tolerability and effectiveness, especially in younger populations. Both treatments have flexible dosing options that can be tailored to individual patient needs, which is a significant advantage over some existing therapies.

What evidence suggests that this trial's treatments could be effective for depression?

This trial will compare Duloxetine and Escitalopram for treating major depressive disorder (MDD). Research has shown that Duloxetine, which participants in this trial may receive, effectively treats MDD. It reduces pain and alleviates symptoms like anhedonia and fatigue. Doctors often choose Duloxetine as an initial treatment for depression.

Escitalopram, another treatment option in this trial, has also proven effective for MDD. It outperforms citalopram and some other antidepressants in short-term treatment. Many people taking Escitalopram notice an improvement in their depression symptoms, and it is generally well-tolerated. Both medications have helped many individuals with depression. ^{1 4 5 6 7}

Who Is on the Research Team?

Jeffrey R Strawn, MD, FAACAP

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

Citations

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Duloxetine in the treatment of major depressive disorder - PMC Results from the analysis of pooled data (Brannan et al 2005; Fava et al 2004) showed that duloxetine reduced pain severity by 22%–41% (depending on the item) ...

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NDA/BLA Multi-Disciplinary Review and Evaluation 370143000 Major depressive disorder (disorder). 21897009 Generalized ... Duloxetine delayed-release capsules are indicated for the treatment of ...

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A Systematic Review of Efficacy, Safety, and Tolerability of ... Most studies (77.8%) evaluated the efficacy of duloxetine, and 55.6% provided data of the treatment safety (97–104, 119). Statistically significant results were ...

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Duloxetine Guide: Pharmacology, Indications, Dosing ... First-line treatment option for major depressive disorder. SNRIs may be particularly effective for patients with anhedonia and fatigue symptom ...

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Cymbalta, Drizalma Sprinkle - duloxetine (Rx) Indicated for major depressive disorder (MDD) 40-60 mg/day PO initially (in single daily dose or divided q12hr for 1 week if patient needs to adjust to therapy)

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This label may not be the latest approved by FDA. For current ... The safety and effectiveness of. DRIZALMA SPRINKLE have not been established in pediatric patients with major depressive disorder. (MDD), diabetic peripheral ...

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Duloxetine (oral route) - Side effects & dosage It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Some people may have trouble sleeping, get upset easily, ...