Apply to Trial

Compensation: Varies

Number of Visits: Unknown

84 Participants Needed

Antidepressants for Anxious Depression
(DOTS-AD Trial)

Overseen ByHeidi K Schroeder

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Cincinnati

Must be taking: Escitalopram, Duloxetine

Disqualifiers: Intellectual disability, Suicide risk, Alcohol use, others

Stay on Your Current MedsYou can continue your current medications while participating

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

Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two medications, duloxetine and escitalopram, for individuals with anxiety disorders, such as generalized or social anxiety, who also experience depression. If the initial treatment does not improve symptoms, participants may receive additional medication, either clonazepam or pregabalin, to address persistent anxiety. The trial seeks individuals fluent in English who have experienced anxiety or panic disorders and have been on specific anxiety medications for at least six weeks. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand how they can benefit more patients.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it excludes those taking medications that require a taper or washout period longer than 5 days.

What is the safety track record for these treatments?

Research has shown that both duloxetine and escitalopram are generally well-tolerated for treating depression and anxiety. Duloxetine is often prescribed for these conditions, and studies indicate that most side effects, such as nausea, dry mouth, and tiredness, are mild to moderate. However, safety for doses exceeding 120 mg per day has not been fully studied.

Escitalopram is approved for treating depression and generalized anxiety disorder and is also well-tolerated. Common side effects include trouble sleeping, nausea, and dizziness. Long-term use has not revealed major safety issues.

Both medications are widely used and have been tested in numerous studies, providing a good understanding of their safety. However, individual experiences can vary, so discussing any concerns with a healthcare provider is important.¹ ² ³ ⁴ ⁵

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for anxious depression because they offer new combinations and adaptability. Duloxetine and escitalopram are being combined with adjunctive medications like clonazepam or pregabalin for patients who don’t initially respond, providing a tailored approach. This adaptability could lead to more personalized and effective treatment plans compared to traditional antidepressants alone. Unlike the usual single-drug therapies, this trial explores how different combinations might better target the complex symptoms of anxious depression.

What is the effectiveness track record for duloxetine and escitalopram in treating anxious depression?

Research has shown that duloxetine, one of the treatments in this trial, effectively treats both mood and anxiety symptoms related to depression. A review of studies found that most demonstrated significant improvements in these symptoms with duloxetine. Additionally, duloxetine consistently reduces depressed mood, regardless of initial symptom severity.

Studies have also shown that escitalopram, another treatment option in this trial, effectively treats major depressive disorder (MDD) with anxiety symptoms. Patients tolerated it well over long-term use, experiencing fewer side effects. The FDA has approved escitalopram for treating depression in adults and teenagers, highlighting its reliability. Both medications show promise in effectively managing symptoms of anxious depression.² ⁶ ⁷ ⁸ ⁹

Who Is on the Research Team?

Jeffrey R Strawn, MD, FAACAP

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18-50 with anxiety and depression, confirmed by specific criteria and tests. They must have a certain score on the HAM-A scale, no significant health issues or drug use, not be pregnant or breastfeeding, and agree to reliable contraception.

Inclusion Criteria

You must use both a diaphragm and a condom during the study.

I use a vaginal ring or contraceptive implant for birth control.

Patients must be fluent in English

See 13 more

Exclusion Criteria

I am on medication that cannot be stopped immediately and requires more than 5 days to safely stop.

You are allergic or have had bad reactions to escitalopram, duloxetine, pregabalin, or clonazepam.

You have a history of having difficulty with learning or understanding things.

See 9 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Adaptively randomized, double-blind treatment with escitalopram or duloxetine for 11 weeks

11 weeks

Weekly visits (in-person)

Phase 2 Treatment

Non-remitting patients receive adjunctive treatment with clonazepam or pregabalin for 8 weeks

8 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

Duloxetine
Escitalopram

Trial Overview The study compares two antidepressants: Escitalopram and Duloxetine. It starts with one of these drugs chosen randomly. If symptoms persist, participants are then given either Clonazepam or Pregabalin in addition to their initial treatment.

How Is the Trial Designed?

2Treatment groups

Active Control

Group I: EscitalopramActive Control1 Intervention

Adaptively randomized, double-blind treatment with escitalopram for 11 weeks in Phase 1. Non-remitting patients will be randomized in Phase 2 to adjunctive clonazepam or pregabalin for 8 weeks. Additionally, adults who are already treated with escitalopram or citalopram for at least 6 weeks prior to screening, may enter Phase 2 and be randomized to adjunctive clonazepam or pregabalin for 8 weeks.

Group II: DuloxetineActive Control1 Intervention

Adaptively randomized, double-blind treatment with duloxetine for 11 weeks in Phase 1. Non-remitting patients will be randomized in Phase 2 to adjunctive clonazepam or pregabalin for 8 weeks. Additionally, adults who are already treated with duloxetine for at least 6 weeks prior to screening, may enter Phase 2 and be randomized to adjunctive clonazepam or pregabalin for 8 weeks.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Published Research Related to This Trial

In a study of 366 outpatients with panic disorder, escitalopram significantly reduced the frequency of panic attacks compared to placebo, demonstrating its efficacy in treating this condition.

Escitalopram was found to be safe and well tolerated, with a low rate of discontinuation due to adverse events, similar to that of the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial.Stahl, SM., Gergel, I., Li, D.[2022]

In a study involving 124 patients with major depressive disorder and high anxiety, escitalopram, desvenlafaxine, and vortioxetine showed similar overall efficacy and tolerability in treating anxious depression over a 6-week period.

Desvenlafaxine was particularly effective in reducing specific anxiety-related symptoms, such as somatic and hypochondriasis scores, compared to escitalopram, indicating it may have unique benefits for certain anxiety symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Escitalopram, Desvenlafaxine, and Vortioxetine in the Acute Treatment of Anxious Depression: A Randomized Rater-blinded 6-week Clinical Trial.Shin, C., Jeon, SW., Lee, SH., et al.[2023]

In a study of 43 subjects with Generalized Anxiety Disorder, both escitalopram and duloxetine showed significant improvements in anxiety and depression scores over 6 months, with similar dropout rates.

Duloxetine demonstrated higher remission and response rates compared to escitalopram after the first month, particularly in the somatic symptoms of anxiety, suggesting it may be a more effective initial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open, non-randomised comparison of escitalopram and duloxetine for the treatment of subjects with Generalized Anxiety Disorder.Pierò, A., Locati, E.[2022]

Citations

1.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC7644852/

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 ...

2.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC2626928/

The role of duloxetine in the treatment of anxiety disordersThey concluded that duloxetine was effective in treating a broad spectrum of symptoms associated with depression, including mood, anxiety, and painful physical ...

3.nature.comnature.com/articles/s41386-019-0523-4

Item-based analysis of the effects of duloxetine in depressionDuloxetine induced a robust reduction in depressed mood that was not dependent on baseline severity and not caused by side-effects breaking the blind.

4.frontiersin.orgfrontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2019.00772/full

Duloxetine in Psychiatric Disorders: Expansions Beyond ...DUL, administered for two menstrual cycles, was effective during the first cycle in reducing mood symptoms, with 39 subjects (78%) meeting criteria for ...

5.sciencedirect.comsciencedirect.com/science/article/pii/S277240852400142X

Therapeutic reference range for duloxetine in the treatment ...We suggest a therapeutic reference range between 20 and 120 ng/mL to achieve optimal antidepressant effects during duloxetine treatment in adults.

6.mayoclinic.orgmayoclinic.org/drugs-supplements/duloxetine-oral-route/description/drg-20067247

Duloxetine (oral route) - Side effects & dosageDuloxetine is used to treat depression and anxiety. It is also used for pain ... Safety and efficacy have not been established for other indications.

7.accessdata.fda.govaccessdata.fda.gov/drugsatfda_docs/label/2010/022516lbl.pdf

Cymbalta (duloxetine hydrochloride) capsulesThe safety of doses above 120 mg/day has not been adequately evaluated [see Clinical Studies (14.1)]. Generalized Anxiety Disorder — For most patients, the ...

8.ema.europa.euema.europa.eu/en/documents/product-information/yentreve-epar-product-information_en.pdf

YENTREVE, INN-duloxetine - European Medicines AgencyThe safety and efficacy of duloxetine for the treatment of stress urinary incontinence has not been studied. No data are available. Special populations.

9.drugs.comdrugs.com/duloxetine.html

Duloxetine: Uses, Side Effects, Dosage, WarningsDuloxetine is used to treat major depressive disorder in adults. It is also used to treat general anxiety disorder in adults and children who are at least 7 ...

Other People Viewed

By Subject

By Trial