Cognitive-Behavioral Therapy vs Antidepressants for Depression

(TIDE Trial)

Recruiting at 1 trial location

Overseen By Jill Cumby, RN, MN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Nova Scotia Health Authority

Must not be taking: Antipsychotics, Antidepressants, Mood-stabilizers

Disqualifiers: Manic episode, Psychotic disorder, Autism, 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: 7

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best initial treatment for young people experiencing their first episode of depression. Participants will receive either cognitive-behavioral therapy (a type of talk therapy) or antidepressant medication to determine which approach is more effective. The study aims to identify personal indicators that guide the choice of treatment for each individual. It suits those aged 12 to 25 who have been dealing with major depression for less than a year and consider it their primary issue needing treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications to join the trial?

Yes, you must stop taking any current antipsychotic, antidepressant, or mood-stabilizer medications. Additionally, you should not have changed any psychotropic medication in the past 6 weeks.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that cognitive-behavioral therapy (CBT) is a safe way to treat depression. As a type of talk therapy, many people find it easy to handle. Unlike medications, CBT has no side effects. Studies have proven it to be an effective and evidence-based method for treating depression.

In contrast, antidepressant medications, like fluoxetine, have long been used to treat depression and are approved by the FDA. However, they carry some risks, especially for young people. Children, teenagers, and young adults taking these medications may experience increased suicidal thoughts. Monitoring for any unusual changes in mood or behavior while using these medications is important.

Overall, CBT is generally safe with no serious side effects, while antidepressants are effective but may require careful monitoring due to potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for depression because they offer unique approaches compared to standard care options like SSRIs or SNRIs. Cognitive-Behavioral Therapy (CBT) is distinctive due to its focus on changing thought patterns and behaviors without medication, potentially reducing side effects and promoting long-term mental health skills. Antidepressant medications, while traditional, are being explored in new combinations or dosages to optimize effectiveness and minimize side effects. This dual approach allows for a tailored treatment plan, potentially offering quicker and more sustainable relief for patients.

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

This trial will compare the effectiveness of antidepressant medication and cognitive-behavioral therapy (CBT) for treating depression. Studies have shown that both antidepressants, such as fluoxetine, and CBT effectively treat depression. Antidepressants can reduce symptoms in many people, with some studies showing they work better than placebos. Research indicates that antidepressants significantly decrease depression symptoms for many individuals. Similarly, CBT has demonstrated strong results, with moderate to large improvements in symptoms. In some studies, CBT has been as effective as other treatments for depression. Both treatments have solid evidence supporting their effectiveness in managing depression symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Rudolf Uher, MD

Principal Investigator

Nova Scotia Health Authority

Are You a Good Fit for This Trial?

This trial is for young people aged 12-25 with recent-onset major depressive disorder, where depression is the main issue. They must have moderate severity of depression and be able to engage in therapy. Excluded are those who've had prior treatment for depression lasting 4+ weeks, current psychotropic medication use, certain psychiatric diagnoses, or substance abuse issues.

Inclusion Criteria

I am between 12 and 25 years old.

I have moderate to severe depression.

Verbal ability sufficient to participate in psychological treatment

Exclusion Criteria

Personal history of a manic or hypomanic episode, diagnosis of psychotic disorder, pervasive developmental disorder, autism spectrum disorder, intellectual disability, mental disorders secondary to neurological or other medical condition, active substance use disorder

I have tried treatments for depression for 4+ weeks and am currently on medication.

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-4 weeks

Up to 4 visits (in-person)

Active Intervention

Participants receive either cognitive-behavioral therapy or optimized antidepressant treatment

16 weeks

Weekly visits (in-person)

Continuation Treatment and Cross-over Options

Continuation of initial treatment or cross-over to the other treatment based on remission status

Variable

Follow-up

Participants are monitored for stability of remission and functional outcomes

104 weeks

Every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Antidepressant medication
• Cognitive-Behavioural Therapy

Trial Overview The TIDE project tests two treatments for youth depression: cognitive-behavioural therapy (CBT) and optimized antidepressant medication. Participants will be randomly assigned to one of these treatments and monitored up to two years to see how they affect symptoms, life functioning, and quality of life.

How Is the Trial Designed?

Group I: Psychotherapy Experimental Treatment 1 Intervention

Cognitive-behavioural therapy

Group II: Pharmacotherapy Experimental Treatment 1 Intervention

Antidepressant medication

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

Approved in United States as Prozac for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Bulimia Nervosa
• Panic Disorder
• Depressive Episodes Associated with Bipolar I Disorder
• Treatment Resistant Depression

Approved in European Union as Fluoxetine for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Bulimia Nervosa
• Panic Disorder
• Premenstrual Dysphoric Disorder

Approved in Canada as Fluoxetine for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Bulimia Nervosa
• Panic Disorder

Who Is Running the Clinical Trial?

Nova Scotia Health Authority

Lead Sponsor

Trials

302

Recruited

95,300+

Rudolf Uher

Lead Sponsor

Trials

2

Recruited

30,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4207330/

Efficacy and Safety of Olanzapine/Fluoxetine Combination ... This study assessed prevention of relapse in patients with treatment-resistant depression (TRD) taking olanzapine/fluoxetine combination (OFC).

2. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/208020

Efficacy of Olanzapine and Olanzapine-Fluoxetine ... Results During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the ...

3. thelancet.com thelancet.com/article/S0140-6736(17)32802-7/fulltext

a systematic review and network meta-analysis In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) ...

4. nature.com nature.com/articles/s41386-024-02044-5

Relative effectiveness of antidepressant treatments in ... Data analysis. The primary efficacy outcome was response rate (defined as ≥50% reduction in depressive symptoms measured by standardized ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC356924/

Fluoxetine: a review on evidence based medicine - PMC Fluoxetine is effective in treating all degrees of depression and is clearly better tolerated (ie, has a more benign adverse-events profile) and safer in cases ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/021520s33lbl.pdf

SYMBYAX (olanzapine and fluoxetine hydrochloride) capsule SYMBYAX — Safety and effectiveness ... The efficacy of SYMBYAX in acute treatment resistant depression was demonstrated with data from 3 clinical studies.

7. mayoclinic.org mayoclinic.org/drugs-supplements/fluoxetine-oral-route/description/drg-20063952

Fluoxetine (oral route) - Side effects & dosage Fluoxetine is used to treat depression, obsessive-compulsive ... However, safety and efficacy have not been established to treat depression ...

8. fda.gov fda.gov/files/advisory%20committees/published/SYMBYAX-Safety-and-Utilization-Review.pdf

SYMBYAX Safety and Utilization Review • Pediatric Use: Safety and efficacy of Symbyax for the treatment of bipolar I depression in patients under 10 years of age have not been ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK459223/

Fluoxetine - StatPearls - NCBI Bookshelf Fluoxetine is an FDA-approved medication that has demonstrated efficacy in treating a spectrum of psychological conditions.

10. medlineplus.gov medlineplus.gov/druginfo/meds/a689006.html

Fluoxetine: MedlinePlus Drug Information Children, teenagers, and young adults who take antidepressants to treat depression or other mental illnesses may be more likely to become suicidal.