Fluoxetine vs Cognitive Behavioural Therapy for Childhood Anxiety Disorders

(SMART Trial)

Overseen By Bradley S. Peterson, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Hospital Los Angeles

Must not be taking: MAOIs, Antipsychotics, Anticonvulsants, others

Disqualifiers: Neurological disorder, OCD, PTSD, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether starting treatment with Cognitive Behavioral Therapy (CBT) or the medication fluoxetine (an antidepressant) more effectively reduces anxiety symptoms in children. Researchers are also examining strategies if the initial treatment proves ineffective, comparing the benefits of either optimizing the same treatment or adding the other one. The trial will evaluate which treatment sequence works best and whether improvements persist for a year after the trial concludes. Children aged 8-17 who experience significant anxiety affecting daily life may be eligible to participate. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

If you are currently taking fluoxetine, you cannot participate in the trial. If you are on other medications like SSRIs, SNRIs, antidepressants, or benzodiazepines, you may need to taper off these medications to join the study, but this will be done with guidance from your current doctor.

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

A previous study found fluoxetine, an FDA-approved medication, to be safe and effective for treating anxiety in children. It is usually well-tolerated, but like any medicine, it can cause side effects. Common side effects include nausea, headaches, and trouble sleeping, while serious side effects are rare.

Research on Cognitive Behavioral Therapy (CBT) has shown it to be safe for children with anxiety. Studies highlight its effectiveness and note that it has fewer side effects than medication. CBT involves talking with a therapist to change negative thoughts and behaviors.

Both treatments have strong safety records for treating anxiety in children. Participants in this trial will be closely monitored to ensure their well-being. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for childhood anxiety disorders because they offer distinct approaches. Fluoxetine is a well-known medication that works by balancing chemicals in the brain, offering a pharmacological solution. On the other hand, Cognitive Behavioral Therapy (CBT), specifically the Coping Cat program, focuses on helping kids change negative thought patterns and build positive behavioral skills, providing a non-drug alternative. Together, these treatments offer a comprehensive approach, giving options for both medical and therapeutic interventions for managing anxiety in children.

What evidence suggests that this trial's treatments could be effective for childhood anxiety disorders?

In this trial, participants will receive either Fluoxetine or Cognitive Behavioral Therapy (CBT) to treat childhood anxiety disorders. A previous study found that fluoxetine significantly reduced anxiety symptoms in children, with 61% of young patients showing improvement compared to 35% in a placebo group. Other research confirms that fluoxetine helps improve overall functioning in children with anxiety. Similarly, CBT, particularly through the Coping Cat program, has effectively reduced anxiety symptoms, with over 60% of children returning to normal anxiety levels after treatment. A Cochrane review supports CBT's effectiveness in treating childhood anxiety disorders. Both treatments have strong evidence supporting their use for managing anxiety in children. ^{3 6 7 8 9}

Who Is on the Research Team?

Bradley S. Peterson, MD

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

This trial is for children aged 8-17 with moderate to severe anxiety disorders, as measured by specific scales (SCARED-5, SCARED-41, CAIS). They must be fluent in English or Spanish and agree to random treatment assignment. Excluded are those on certain medications like MAOIs or antipsychotics recently, pregnant females not using birth control, anyone with PTSD or unstable medical conditions, and those below a second-grade level in reading/language arts.

Inclusion Criteria

I am between 8 and 17 years old.

I have been diagnosed with an anxiety disorder.

You have high scores on two questionnaires that measure anxiety symptoms, indicating that you may have severe anxiety.

Exclusion Criteria

Patients scoring a 5

Patients with a current/active psychotic diagnosis (schizophrenia, schizoaffective, schizophreniform, psychosis not otherwise specified (NOS), or depression with psychotic features), as determined by medical chart and medical history review by the site director and PI.

I am currently undergoing psychotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Cognitive Behavioral Therapy (CBT) or fluoxetine medication over a 24-week intervention period

24 weeks

Optimization

If initial treatment fails by week 12, treatment is optimized or combined with the other modality for better symptom improvement

12 weeks

Follow-up

Participants are monitored for stability of treatment response for at least 12 months following the 24-week trial

≥12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Behavioral Therapy (CBT)
• Fluoxetine

Trial Overview The study compares starting treatment with Cognitive Behavioral Therapy (CBT) versus fluoxetine medication for childhood anxiety disorders. If there's no remission by week 12, the study will test if optimizing the initial treatment or adding the other modality improves symptoms more by week 24. It also examines which sequence of treatments is most effective over a year.

How Is the Trial Designed?

Group I: Medication - Fluoxetine Active Control 1 Intervention

Approved medication by the U.S. Food and Drug Administration (FDA) for treating anxiety disorders in children. The study's starting dose, and minimum permitted, will be 10 mg/day; should that not be tolerated, the patient will be withdrawn from active treatment (but not from study follow-up). After 1 week at 10 mg/day, the dose will increase to 20 mg/day. After completion of week 4, 10 mg/day dose increases will be permitted every other week as tolerated, up to a maximum daily dose of 80 mg/day. If patients are on doses \>20mg/day, the total daily dose can be prescribed either once daily or split into twice daily administrations.

Group II: Cognitive Behavioral Therapy (CBT) Active Control 1 Intervention

Type of talk therapy that aims to identify and replace negative thoughts, using positive behavioral skills to create and maintain positive moods and healthy relationships. The Coping Cat (CC) program will be used as the behavioral intervention for this study.CC is an established evidence-based CBT treatment for pediatric anxiety. It is delivered in individual therapy sessions with anxious children.

Cognitive Behavioral Therapy (CBT) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cognitive Behavioral Therapy for:

• Chronic pain
• Anxiety disorders
• Depressive disorders
• Trauma-related disorders

Approved in European Union as Cognitive Behavioural Therapy for:

• Chronic pain
• Anxiety disorders
• Depressive disorders
• Trauma-related disorders

Approved in Canada as Cognitive Behavioral Therapy for:

• Chronic pain
• Anxiety disorders
• Depressive disorders
• Trauma-related disorders

Who Is Running the Clinical Trial?

Children's Hospital Los Angeles

Lead Sponsor

Trials

257

Recruited

5,075,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Published Research Related to This Trial

A systematic review of 21 studies found that fluoxetine use during the first trimester of pregnancy does not significantly increase the risk of major fetal malformations, with an odds ratio of 1.12, indicating safety for the fetus.

However, there is a noted increased risk of cardiac malformations associated with fluoxetine use, with an odds ratio of 1.6 from cohort studies, suggesting that this risk may be influenced by factors such as ascertainment bias in reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fetal safety of fluoxetine: a systematic review and meta-analysis. Riggin, L., Frankel, Z., Moretti, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5236072/

Effectiveness of a Cognitive Behavioral Therapy-Based ... The results showed that Coping Cat, as an indicated prevention program, reduces children's self-reported anxiety symptoms, with Cohen's effect size d of 0.66 ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/pits.22725

Qualitative analysis of school children's experience ... “Coping Cat”-cognitive behavior therapy (CBT) proved to be an effective treatment for high anxiety in Indian school children (11–13 years age ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6491167/

Cognitive behavioural therapy for anxiety disorders in children ... A previous Cochrane review (James 2005) showed that cognitive behavioural therapy (CBT) was effective in treating childhood anxiety disorders.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1077722908000333

Computer-Assisted CBT for Child Anxiety: The Coping Cat ... Empirical data support the efficacy of cognitive-behavioral therapy (CBT) for child anxiety, but there is need and merit in the development and evaluation ...

5. cebc4cw.org cebc4cw.org/program/coping-cat/detailed

CEBC » Coping Cat › Program › Detailed Results indicate that over 60% of treated children had returned to within normal anxiety levels by the end of treatment and that this percentage was ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11177010/

Cognitive Behavioral Therapy for Children and Adolescents ... CBT for childhood anxiety disorders also shows acceptability and safety, with no adverse effects and lower dropout rates than pharmacotherapy or pill placebo.

7. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/1471-244X-13-183

Effectiveness and underlying mechanisms of a group-based ... “Coping Cat” is one of the few evidence-based CBT programs designed to treat anxiety symptoms in children.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0005796715001060

Comparing outcomes for children with different anxiety ... In a multi-site study of CBT and medication, the odds of remission for children with GAD and SAD were 2.5 times greater than children with SoAD immediately ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2589979120300494

Treatment satisfaction with cognitive-behavioral therapy ... Studies on clinical outcomes have shown positive effects of cognitive-behavioral therapy (CBT) in children and adolescents with anxiety and depression. However, ...