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

Trial Summary

What is the purpose of this trial?

The TIDE project aims to establish personal indicators for initial treatment choice for youth with first episode depression. Specifically, 100 adolescents and young adults (age 12 to 25) with untreated major depressive disorder of recent onset will be randomly allocated in 1:1 ratio to one of two evidence-based regimens for youth depression: (A) Individual cognitive-behavioural therapy; and (B) Optimized pharmacological treatment with an antidepressant. All participants will be offered active treatment for up to 1 year and follow-up for 2 years to establish short- and long-term outcomes, including change in depressive symptoms, maintenance of remission, core role functioning, achievement of educational, occupational and social milestones, and quality of life. Baseline characteristics including duration of untreated depression, pre-existing anxiety, attention-deficit/hyperactivity disorder, substance use, symptoms of reduced interest and activity, sleep, rhythm and melody of speech, brain function, history of childhood adversity, coping style, repetitive thinking, and family history of depression and bipolar disorder will be tested as potential moderators of outcome. Characteristics that differentially predict outcomes in those allocated to initial cognitive-behavioural therapy and those allocated to initial treatment with antidepressants will be combined into a personalized allocation algorithm.

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.

What data supports the idea that Cognitive-Behavioral Therapy vs Antidepressants for Depression is an effective treatment?

The available research shows that combining Cognitive-Behavioral Therapy (CBT) with antidepressant drugs can be more effective than using either treatment alone. Studies suggest that this combined approach may be particularly beneficial for certain groups of people with depression. While CBT and antidepressants each work well on their own, using them together might offer additional advantages, especially for those who don't respond well to just one type of treatment. ^{1 2 3 4 5}

What safety data exists for Cognitive-Behavioral Therapy and Antidepressants like Fluoxetine?

The safety data for antidepressants, including fluoxetine (also known as Prozac, Sarafem, Symbyax), is well-documented. Studies have evaluated the safety and side effect profiles of various SSRIs, including fluoxetine, in treating depression and other disorders. Common side effects include gastrointestinal, central nervous system, and sexual side effects. The choice of antidepressant often depends on these side effect profiles. SSRIs are generally considered safer than older antidepressants like tricyclics, especially for patients with increased cardiovascular risk. However, specific safety data comparing Cognitive-Behavioral Therapy (CBT) to antidepressants is not detailed in the provided research abstracts. ^{6 7 8 9 10}

Is the drug Antidepressant medication a promising treatment for depression?

Yes, antidepressant medication is a promising treatment for depression. Studies show that certain antidepressants like escitalopram and sertraline are effective and well-accepted by patients. They help many people feel better and are recommended as a first choice for treating depression. ^{11 12 13 14 15}

Research Team

Rudolf Uher, MD

Principal Investigator

Nova Scotia Health Authority

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

Combining psychotherapy or psychiatric consultation with drug therapy leads to better treatment responses for depression compared to using either method alone, as supported by several studies.

Matching antidepressant medications to individual patient characteristics based on side-effect profiles may improve treatment compliance, and switching or adding different classes of antidepressants can benefit patients who do not respond to initial treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving the best outcome in treatment of depression. Sutherland, JE., Sutherland, SJ., Hoehns, JD.[2007]

In a study involving 318 outpatients with major depressive disorder who did not respond well to citalopram, cognitive therapy showed similar effectiveness to medication strategies for improving depression outcomes after initial treatment.

Medication augmentation with bupropion or buspirone led to faster remission compared to cognitive therapy, while switching to cognitive therapy was associated with fewer side effects than switching to another antidepressant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Thase, ME., Friedman, ES., Biggs, MM., et al.[2023]

In an 8-week study involving 163 participants, both sertraline and venlafaxine XR showed similar efficacy and quality of life outcomes in treating major depression, indicating that either medication can be effective.

Sertraline was associated with fewer moderate to severe discontinuation symptoms and a lower risk of increased blood pressure compared to venlafaxine XR, suggesting it may be a safer option during treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. Sir, A., D'Souza, RF., Uguz, S., et al.[2022]

Combined psychotherapy and pharmacotherapy for unipolar depression showed significantly better results than placebo treatments, indicating that both approaches together can enhance treatment effectiveness.

However, the combination of psychotherapy and medication was only slightly more effective than using either psychotherapy or pharmacotherapy alone, suggesting that while combined treatment is beneficial, it may not be dramatically superior to individual therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined psychotherapy and pharmacotherapy for depression. A systematic analysis of the evidence. Conte, HR., Plutchik, R., Wild, KV., et al.[2019]

A review of 17 studies on combined psychotherapy and pharmacotherapy for depression suggests that this approach is not more effective than using either treatment alone, highlighting the need for further research due to methodological limitations.

However, combined treatment may offer specific benefits for certain subpopulations of depressed patients, indicating that personalized treatment strategies could be important in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of combined psychotherapy and pharmacotherapy in the treatment of depression. Manning, DW., Markowitz, JC., Frances, AJ.[2021]

In a study of 175 patients with alcohol dependence and depressive disorders, fluvoxamine showed the fastest efficacy in relieving depressive symptoms by the 7th day, while other SSRIs like sertraline and paroxetine took 14 days, and fluoxetine took 30 days.

Fluvoxamine also demonstrated the best safety profile among the SSRIs, with fewer adverse reactions compared to fluoxetine, citalopram, and sertraline, making it a favorable option for treating depression in patients with alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fluvoxamine in the treatment of depressive disorders in alcohol dependence: results of randomized open-label comparative study]. Vinnikova, MA., Severtsev, VV., Komarov, SD., et al.[2022]

Selective serotonin reuptake inhibitors (SSRIs) are the preferred treatment for depression and have also been found effective for conditions like obsessive-compulsive disorder and generalized anxiety disorder, with new uses emerging for PTSD and premenstrual dysphoric disorder.

Mirtazapine works differently by stimulating norepinephrine and serotonin release, and managing side effects like sexual dysfunction can involve dosage adjustments or switching medications, highlighting the importance of personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressants: update on new agents and indications. Ables, AZ., Baughman, OL.[2022]

Bupropion SR was found to have the most favorable side effect profile among nine antidepressants studied, while fluvoxamine had the least favorable, indicating that side effects play a crucial role in choosing antidepressant medications.

The study highlights the need for more clinical trials directly comparing the side effects of newer antidepressants, as current data from the Physicians' Desk Reference has limitations in accurately reflecting the side effects of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the tolerability of the newer antidepressants. Dewan, MJ., Anand, VS.[2022]

The review will focus on the safety and efficacy of new antidepressants, particularly SSRIs like fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram, in high-risk patients.

It will also include data on moclobemide, a new reversible inhibitor of monoamine oxidase-A, to assess its potential benefits and risks in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New antidepressants: use in high-risk patients. Hale, AS.[2022]

Selective serotonin reuptake inhibitors (SSRIs) are generally considered a safer treatment for depression compared to older tricyclic antidepressants, but they still carry potential safety risks, especially in patients with a history of stroke or myocardial infarction.

Patients with cardiovascular issues may face increased risks of adverse events, such as QT prolongation and bleeding, when prescribed SSRIs, highlighting the importance of considering individual health conditions and medications when initiating treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations for prescribing SSRI antidepressants to patients at increased cardiovascular risk. Mortensen, JK., Andersen, G.[2022]

Tetrazyclic antidepressants, selective serotonin reuptake inhibitors, and selective MAO inhibitors are recommended as first-choice treatments for depressive episodes due to their favorable side-effect profiles.

While combining drug therapy with psychotherapy may not show clear advantages over using either treatment alone, it could potentially lower the chances of relapse in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of depression]. Klimke, A., Lehmann, E., Klieser, E.[2018]

In a comprehensive analysis of 117 trials involving 25,928 participants, mirtazapine, escitalopram, venlafaxine, and sertraline were found to be significantly more effective than duloxetine, fluoxetine, fluvoxamine, paroxetine, and reboxetine for treating unipolar major depression.

Escitalopram and sertraline not only showed higher efficacy but also had better acceptability, resulting in fewer patients discontinuing treatment compared to other antidepressants, highlighting their potential as preferred options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparative efficacy and acceptability of new-generation antidepressants. Synthesis meta-analysis Cipriani]. Gaillard, R.[2009]

In a study involving 170 Romanian clients with major depressive disorder, cognitive therapy (CT) and rational emotive behavioral therapy (REBT) were found to be equally effective as fluoxetine (Prozac) in reducing depression symptoms over a 14-week treatment period, with significant improvements in Beck Depression Inventory (BDI) scores.

CT and REBT were more cost-effective than fluoxetine, with lower costs per depression-free day gained, making them preferable options for treating major depressive disorder from a financial perspective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness and cost-utility of cognitive therapy, rational emotive behavioral therapy, and fluoxetine (Prozac) in treating depression: a randomized clinical trial. Sava, FA., Yates, BT., Lupu, V., et al.[2022]

A variety of treatment options for major depression, including bibliotherapy, group CBT, and individual CBT, are highly cost-effective, costing less than 10,000 Australian dollars per disability-adjusted life year (DALY).

While maintenance treatment with SSRIs is more expensive (17,000 to 20,000 Australian dollars per DALY), it remains below the threshold of 50,000 Australian dollars, indicating that effective long-term treatment options exist but are underutilized.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of cognitive-behavioural therapy and drug interventions for major depression. Vos, T., Corry, J., Haby, MM., et al.[2022]

For patients with treatment-resistant depression, switching to other antidepressants or adding non-antidepressant medications shows the best evidence of effectiveness, with a success rate of about 25% to 30%.

While psychotherapy and electroconvulsive therapy (ECT) are options, their evidence for effectiveness after initial treatment failure is limited, and ECT has particularly weak support according to expert opinion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical inquiries: How should you manage a depressed patient unresponsive to an SSRI? Triezenberg, D., Vachon, D., Helmen, J., et al.[2022]

References

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

Achieving the best outcome in treatment of depression. [2007]

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

Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. [2023]

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

Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. [2022]

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

Combined psychotherapy and pharmacotherapy for depression. A systematic analysis of the evidence. [2019]

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

A review of combined psychotherapy and pharmacotherapy in the treatment of depression. [2021]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Fluvoxamine in the treatment of depressive disorders in alcohol dependence: results of randomized open-label comparative study]. [2022]

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

Antidepressants: update on new agents and indications. [2022]

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

Evaluating the tolerability of the newer antidepressants. [2022]

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

New antidepressants: use in high-risk patients. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Safety considerations for prescribing SSRI antidepressants to patients at increased cardiovascular risk. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[Therapy of depression]. [2018]

12. France pubmed.ncbi.nlm.nih.gov

[Comparative efficacy and acceptability of new-generation antidepressants. Synthesis meta-analysis Cipriani]. [2009]

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

Cost-effectiveness and cost-utility of cognitive therapy, rational emotive behavioral therapy, and fluoxetine (Prozac) in treating depression: a randomized clinical trial. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of cognitive-behavioural therapy and drug interventions for major depression. [2022]

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

Clinical inquiries: How should you manage a depressed patient unresponsive to an SSRI? [2022]