Enhanced Cognitive Behavioral Therapy for Depression

(CBT+ Trial)

Overseen By Jacob Meyer, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Iowa State University

Disqualifiers: Pregnancy, Severe obesity, Psychosis, others

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

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This study investigates the effects of a novel intervention approach, intentionally sequencing aerobic exercise immediately prior to therapy sessions (i.e., cognitive behavioral therapy \[CBT\]) to determine its effects on both specific and common factors underlying the antidepressant effect of CBT (i.e., mechanisms of CBT). To assess the utility of this treatment augmentation, investigators plan to conduct a randomized controlled trial involving 40 adults with Major Depressive Disorder who will watch a nature documentary while either resting quietly (termed 'CalmCBT') or exercising at a moderate intensity ('ActiveCBT') immediately prior to 8 weekly sessions of CBT. It is hypothesized that target CBT mechanisms of antidepressant action (i.e., self-reported working alliance and behavioral activation) will be more effectively engaged by ActiveCBT vs. CalmCBT.

Will I have to stop taking my current medications?

You can continue taking your current medications if you are on a stable treatment plan and are willing to maintain it throughout the study. If you are not currently on any mental health treatment, you can still participate.

What data supports the effectiveness of the treatment CBT+ for depression?

Research shows that Cognitive Behavioral Therapy (CBT) is effective for treating depression, with moderate to large effects compared to usual care and waitlist controls. Additionally, combining CBT with other treatments can be more effective than using medication alone, especially in the long term. ^{1 2 3 4 5}

Is Enhanced Cognitive Behavioral Therapy (CBT+) safe for humans?

Research shows that when Cognitive Behavioral Therapy (CBT) is done correctly, it has a low rate of adverse events (unwanted effects), similar to or even less than a placebo (a harmless pill). However, problems can occur if the therapy is not done properly, often due to a therapist's lack of experience or skill. ^{6 7 8 9 10}

How is Enhanced Cognitive Behavioral Therapy for Depression different from other treatments?

Enhanced Cognitive Behavioral Therapy (CBT+) for Depression is unique because it combines traditional CBT techniques with additional strategies to increase positive emotions, engagement, and meaning, similar to Positive Psychotherapy. This approach not only targets depressive symptoms but also focuses on enhancing overall well-being, making it potentially more effective in the long term compared to standard treatments. ^{3 11 12 13 14}

Eligibility Criteria

Adults aged 18-65 with Major Depressive Disorder (MDD), experiencing mild to severe depression, can join this study. They must be new to CBT and not currently pregnant or nursing. Participants should be physically able to exercise and not have a history of psychosis, mania, bipolar disorder, substance use disorders, or pose a risk of harm.

Inclusion Criteria

I have been diagnosed with major depression.

I am currently experiencing mild or more severe depression.

Either not engaging in any mental health treatment OR on a stable mental health treatment regimen and willing to maintain it for the length of the intervention

Exclusion Criteria

Diagnosed with current Substance Use Disorder, via the SCID

Diagnosed with lifetime or current Psychosis, Mania, or Bipolar Disorder, via the SCID

My BMI is 40 or more, indicating severe obesity.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in 8 weekly sessions of CBT, with either moderate exercise (ActiveCBT) or quiet rest (CalmCBT) prior to therapy sessions.

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for changes in depression symptoms and other outcomes after the treatment phase.

12 weeks

1 visit (in-person)

Long-term follow-up

Participants are assessed for long-term changes in depression symptoms and other outcomes.

1 year

Treatment Details

Interventions

• CBT+

Trial Overview The trial is testing two versions of CBT for depression: 'CalmCBT' involves resting before therapy sessions while 'ActiveCBT' includes moderate exercise beforehand. The goal is to see if exercising affects the benefits of CBT over eight weeks.

Participant Groups

Group I: ActiveCBT Experimental Treatment 1 Intervention

Participants will complete a standardized 30-minute exercise session on a stationary bike prior to therapy. Participants will view one of 8 standardized 30-minute nature documentary videos while exercising.

Group II: CalmCBT Active Control 1 Intervention

Participants will view one of 8 standardized 30-minute nature documentary videos while resting quietly prior to therapy.

Who Is Running the Clinical Trial?

Iowa State University

Lead Sponsor

Trials

63

Recruited

145,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

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]

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]

In a study of 260 chronically depressed patients, those receiving Cognitive Behavioral Analysis System of Psychotherapy (CBASP) reported more severe adverse events compared to those receiving supportive psychotherapy, particularly in personal and occupational life.

However, CBASP was associated with fewer adverse events related to suicidal thoughts, suggesting that while it may lead to some temporary challenges, it can be a safer option in terms of suicidal ideation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events during a disorder-specific psychotherapy compared to a nonspecific psychotherapy in patients with chronic depression. Meister, R., Lanio, J., Fangmeier, T., et al.[2021]

Current clinical trials for behavioral health interventions often do not monitor adverse events as thoroughly as those for medications and medical devices, focusing mainly on serious incidents like suicide attempts and hospitalizations.

There is a need for expanded monitoring of adverse events in psychotherapy trials to better inform patients about potential risks, including temporary increases in anxiety, which are often overlooked but can impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The need for expanded monitoring of adverse events in behavioral health clinical trials. Peterson, AL., Roache, JD., Raj, J., et al.[2012]

When cognitive behavioral therapy (CBT) is conducted effectively, the rate of adverse events is very low, comparable to or even lower than that of a placebo, indicating its safety and efficacy.

Many adverse events arise from poor-quality CBT due to therapists' insufficient training, highlighting the importance of regular patient assessments and supervision to ensure high standards in therapy delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse Events and Precautions Regarding Cognitive Behavioral Therapy]. Okmaoto, Y., Jinnin, R., Yoshino, A., et al.[2018]

Cognitive Behavioral Therapy (CBT) is an effective treatment for all levels of major depression, proving to be as effective and more durable than medication alone.

Combining CBT with medication can enhance treatment response and prolong benefits, especially when CBT is introduced after successful pharmacotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy for depression. Sudak, DM.[2022]

Positive psychotherapy (PPT) focuses on enhancing positive emotions and engagement rather than just reducing depressive symptoms, showing significant long-term benefits, including a decrease in mild-to-moderate depression levels for up to a year in group settings.

In individual treatments for major depressive disorder, PPT resulted in higher remission rates compared to standard treatments and those combined with medication, suggesting it can be an effective supplement to traditional depression therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive psychotherapy. Seligman, MEP., Rashid, T., Parks, AC.[2022]

References

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

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

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

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

3. Italy pubmed.ncbi.nlm.nih.gov

Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta-analysis including 409 trials with 52,702 patients. [2023]

4. England pubmed.ncbi.nlm.nih.gov

The effectiveness of cognitive behavioural therapy in depression. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Does early response predict outcome in psychotherapy and combined therapy for major depression? [2022]

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

Adverse events during a disorder-specific psychotherapy compared to a nonspecific psychotherapy in patients with chronic depression. [2021]

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

The need for expanded monitoring of adverse events in behavioral health clinical trials. [2012]

8. Japan pubmed.ncbi.nlm.nih.gov

[Adverse Events and Precautions Regarding Cognitive Behavioral Therapy]. [2018]

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

Can Cognitive Behavioral Therapy for Anxiety and Depression Be Improved with Pharmacotherapy? A Meta-analysis. [2019]

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

A comparison of the effects of sudden gains and depression spikes on short- and long-term depressive symptoms in a randomized controlled trial of behavioral activation and cognitive behavioural therapy. [2022]

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

Cognitive behavioral therapy for depression. [2022]

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

Positive psychotherapy. [2022]

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

Cognitive and behavioral therapies for depression: overview, new directions, and practical recommendations for dissemination. [2018]

14. Brazil pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral therapy for treatment-resistant depression in adults and adolescents: a systematic review. [2021]