CBT + Antidepressants for Depression
(CANBIND6 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Nova Scotia Health Authority
Must not be taking: Antidepressants
Disqualifiers: Bipolar, Schizophrenia, Substance use, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Depression currently affects close to 2 million Canadians and is the leading cause of disability worldwide. Pharmacological treatments (antidepressant medication) and psychological treatments such as cognitive-behavioural therapy are available for depression, but the majority of those who receive treatment have an unsatisfactory response. On average, the combination of pharmacological and psychological treatment achieves better results than either treatment alone. However, the apparently superior results of combination treatment may be due to the fact that different individuals preferentially respond to pharmacological or psychological treatment. The invesitagtors have discovered several clinical factors and biomarkers that predict poor response to commonly used antidepressant medication: history of childhood maltreatment, loss of interest and reduced activity, a biomarker of systemic inflammation, and a genetic marker of sensitivity to environment. Indirect evidence suggests that the same factors may indicate the need for psychological treatment, but their usefulness as differential predictors of psychological and pharmacological treatment outcomes remains to be established.
The investigators will test the hypothesis that a pre-determined set of clinical variables (history of childhood maltreatment, loss of interest and reduced activity) and biomarkers (serum C-reactive protein, a marker of systemic inflammation, and short alleles of the serotonin transporter gene promoter polymorphism) differentially predicts response to antidepressants and to cognitive-behavioural psychotherapy with clinically significant accuracy.
If this hypothesis is supported, the resulting predictor will allow personalized selection of treatment for depression, leading to improved outcomes and healthcare efficiency. Additional objectives include replication of additional predictors and integrative analyses aimed at refining the treatment choice algorithms.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications, but you cannot join if you've recently started a new antidepressant or increased your dose in the past 6 weeks.
What data supports the effectiveness of combining antidepressants with cognitive behavioral therapy for treating depression?
Research suggests that antidepressants, especially those affecting multiple neurotransmitters like venlafaxine, can be effective in treating depression. Combining these with therapies like cognitive behavioral therapy (CBT) may enhance treatment effectiveness, as targeting multiple aspects of depression can lead to better outcomes.
12345Is the combination of CBT and antidepressants generally safe for humans?
Antidepressants like SSRIs and SNRIs are generally considered safe and have fewer side effects compared to older drugs like tricyclic antidepressants. However, all medications can have potential risks, so it's important to discuss these with a healthcare provider.
16789How is the CBT + Antidepressants treatment for depression different from other treatments?
This treatment combines cognitive behavioral therapy (CBT), which helps change negative thought patterns, with antidepressants, which adjust brain chemicals to improve mood. This dual approach is unique because it addresses both the psychological and biological aspects of depression, potentially offering more comprehensive relief than using either method alone.
1011121314Eligibility Criteria
This trial is for adults over 18 with depression lasting at least two months, diagnosed with Major Depressive Disorder (MDD) or Persistent Depressive Disorder (PDD), and a Hamilton Rating Scale for Depression score of 14+. They must see depression as their main issue and can consent. Excluded are those with psychosis, pregnancy, bipolar/schizophrenia spectrum disorders, recent substance abuse disorder, extensive recent CBT or non-response to study meds.Inclusion Criteria
I have been depressed for at least two months and am 18 or older.
I have been diagnosed with major depression or persistent depressive disorder as my main health issue.
a minimum current severity of 14 on the 17-item Hamilton Rating Scale for Depression (HRSD-17)
+1 more
Exclusion Criteria
You are currently experiencing symptoms of psychosis.
You are pregnant.
You have been diagnosed with a mental illness such as bipolar disorder, schizophrenia, or schizoaffective disorder, or you are currently struggling with alcohol or drug addiction.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either cognitive-behavioural therapy or antidepressant medication based on predictive scores
18 weeks
Visits every 2 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
34 weeks
Medium-term follow-ups at 26 and 52 weeks
Participant Groups
The trial tests if certain clinical factors and biomarkers predict better outcomes in treating depression with Cognitive Behavioral Therapy versus antidepressants. It aims to personalize treatment by identifying who responds best to which therapy based on childhood maltreatment history, activity levels, inflammation markers (C-reactive protein), and genetic markers.
2Treatment groups
Experimental Treatment
Group I: PsychotherapyExperimental Treatment1 Intervention
Cognitive Behavioral Therapy
Group II: PharmacotherapyExperimental Treatment1 Intervention
Antidepressant medication
Antidepressants is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Antidepressants for:
- Major Depressive Disorder (MDD)
- Persistent Depressive Disorder (PDD)
- Anxiety Disorders
- Post-Traumatic Stress Disorder (PTSD)
🇺🇸 Approved in United States as Antidepressants for:
- Major Depressive Disorder (MDD)
- Persistent Depressive Disorder (PDD)
- Anxiety Disorders
- Post-Traumatic Stress Disorder (PTSD)
- Obsessive-Compulsive Disorder (OCD)
🇨🇦 Approved in Canada as Antidepressants for:
- Major Depressive Disorder (MDD)
- Persistent Depressive Disorder (PDD)
- Anxiety Disorders
- Post-Traumatic Stress Disorder (PTSD)
🇯🇵 Approved in Japan as Antidepressants for:
- Major Depressive Disorder (MDD)
- Anxiety Disorders
🇨🇳 Approved in China as Antidepressants for:
- Major Depressive Disorder (MDD)
- Anxiety Disorders
🇨🇭 Approved in Switzerland as Antidepressants for:
- Major Depressive Disorder (MDD)
- Persistent Depressive Disorder (PDD)
- Anxiety Disorders
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Nova Scotia Health AuthorityHalifax, Canada
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Who Is Running the Clinical Trial?
Nova Scotia Health AuthorityLead Sponsor
University Health Network, TorontoCollaborator
Centre for Addiction and Mental HealthCollaborator
Queen's UniversityCollaborator
References
Mechanism of action of antidepressants. [2022]A wide range of effective drugs is available for the treatment of major depression. The discovery of these agents has not always been the result of rational drug design. Tricyclic antidepressants formed the mainstay of treatment until the 1990s, and selective serotonin reuptake inhibitors (SSRIs) have dominated treatment over the last decade. However, the poor tolerability associated with tricyclic antidepressants and concerns about the efficacy of SSRIs has led to the search for alternative agents. Attention has focused on those drugs that affect norepinephrine and/or serotonin systems, with the recent introduction of a number of agents, including venlafaxine, milnacipran, nefazodone, mirtazapine, and reboxetine. Venlafaxine, which is the first in a new class of drugs known as serotonin and norepinephrine reuptake inhibitors, may be associated with an earlier onset of action and higher remission rates than SSRIs. It is hoped that the development of drugs with multiple sites of action will translate into improved clinical efficacy in the treatment of depression.
Basic psychopharmacology of antidepressants, part 1: Antidepressants have seven distinct mechanisms of action. [2022]Distinct pharmacologic mechanisms allow the antidepressants to be separated into seven different classes. These basic pharmacologic concepts can explain not only the therapeutic actions, but also the side effects of the wide range of antidepressants currently available. The two classical mechanisms are those of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). The most widely prescribed agents are the serotonin selective reuptake inhibitors (SSRIs). Three other classes of antidepressants, like the SSRIs, increase serotonergic neurotransmission, but they also have additional actions, namely dual serotonin and norepinephrine reuptake inhibition (venlafaxine); serotonin-2 antagonism/reuptake inhibition (nefazodone); and alpha2 antagonism plus serotonin-2 and -3 antagonism (mirtazapine). The selective norepinephrine and dopamine reuptake inhibitor bupropion defines a novel class of antidepressant that has no direct actions on the serotonin system.
Antidepressant effectiveness in severe depression and melancholia. [2022]While outcome has improved in patients with depressive disorders since the introduction of the newer antidepressants, some physicians still treat severely depressed patients with the older tricyclic antidepressants because of conflicting reports about the efficacy of the newer agents, particularly the selective serotonin reuptake inhibitors, in severe depression. However, a standardized operational definition of severe depression is lacking, and treatment studies are difficult to evaluate due to variation in methodology. Remission rates are relatively low in many of the short-term clinical trials of the newer antidepressants in severe depression, but may improve if the research design were to include a longer trial and aggressive dosing. There is some evidence that venlafaxine, a serotonin-norepinephrine antidepressant, may offer some advantage for severely depressed patients.
Citalopram-Associated Alopecia: A Case Report and Brief Literature Review. [2020]Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line treatments for various psychiatric disorders. SSRIs offer an improved side effect profile compared to older treatments, which improves patients' adherence and quality of life.
Can monoamine-based therapies be improved? [2015]Monoamine-based therapies that selectively target serotonin, norepinephrine, or dopamine uptake are effective as antidepressants. However, many depressed patients do not achieve remission with these single-action agents. Treatment strategies that target more than one neurotransmitter, either through augmentation, combination treatment, or the development of single agents with dual or triple reuptake mechanisms, may prove to be even more effective than traditional antidepressants and merit further research.
Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. [2022]To summarize remission rates and dropouts due to adverse drug reactions (ADRs) or lack of efficacy (LoE) of serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin-reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs) in treating major depressive disorder.
[Review of pharmacological efficacies and side effects of antidepressants]. [2013]We reviewed the pharmacological efficacies and side effects of antidepressants. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs) are most popularly prescribed for anxiety disorders as well as mild or moderate depression. These drugs have less orthostatic, cognitive, cardiovascular, and anticholinergic side effects. Tricyclic antidepressants are still important for treating severe depression, and mianserin and trazodone are useful for treating delirium. Clinicians should select antidepressants considering their pharmacologic profiles and avoiding adverse effects.
Safety considerations for prescribing SSRI antidepressants to patients at increased cardiovascular risk. [2022]With the development of selective serotonin reuptake inhibitors (SSRI), a relatively uncomplicated treatment of depression and a safer alternative to tricyclic antidepressants was introduced. Any medical treatment has potential safety risks, however, and these risks should also be considered when prescribing SSRIs.
First-line pharmacotherapies for depression - what is the best choice? [2022]Major depressive disorder is a significant public health problem and the leading cause of suicide worldwide. Since the discovery of the first effective medications for depression in the late 1950s, a variety of pharmacotherapies have been developed that are useful for treating the full range of depressive disorders. The availability of safer classes of antidepressants, as well as other factors, has resulted in a large increase in the number of depressed individuals who are treated for depression by their primary care providers. This review examines the antidepressants that are currently used as the initial or "first-line" therapies for major depressive disorder (MDD). These newer medications may be grouped into three classes: the selective serotonin reuptake inhibitors, the serotonin and norepinephrine reuptake inhibitors, and the norepinephrine-dopamine reuptake inhibitor. While the modern classes of antidepressants offer superior tolerability and safety over older medications such as the tricyclic antidepressants, there remains no universally effective pharmacologic treatment for MDD, and effective disease management requires careful attention to ongoing assessment of medication response and management of side effects.
[Drug combinations in the treatment of depression]. [2006]Four types of combination therapy may be used in the treatment of depression: anxiolytics and antidepressants, neuroleptics and antidepressants, co-administration of two or more antidepressants, association of antidepressants with drugs correcting antidepressant-induced side-effects. First, the pros and cons of these combinations are described as they appear in daily practice. In the second part, the theoretical reasons for supporting or contraindicating such combinations are discussed in the light of pharmacological data. The value of recent molecules such as nomifensin, viloxazin, amineptin and mianserin which interact with a minimum number of neurotransmitters is stressed.
Feasibility of Computerized Cognitive-Behavioral Therapy Combined With Bifrontal Transcranial Direct Current Stimulation for Treatment of Major Depression. [2022]Cognitive behavioral therapy (CBT) is effective in the treatment of major depressive disorder (MDD). Transcranial Direct Current Stimulation (tDCS) has demonstrated preliminary antidepressant effects and beneficial effects on cognitive function.
A randomized controlled trial on the efficacy of mindfulness-based cognitive therapy and a group version of cognitive behavioral analysis system of psychotherapy for chronically depressed patients. [2018]Mindfulness-based cognitive therapy (MBCT) has recently been proposed as a treatment option for chronic depression. The cognitive behavioral analysis system of psychotherapy (CBASP) is the only approach specifically developed to date for the treatment of chronically depressed patients. The efficacy of MBCT plus treatment-as-usual (TAU), and CBASP (group version) plus TAU, was compared to TAU alone in a prospective, bicenter, randomized controlled trial.
Cognitive-behavioral therapy added to fluoxetine in major depressive disorder after 4 weeks of fluoxetine-treatment: 16-week open label study. [2022]Major depressive disorder (MDD) not responding to antidepressant treatment poses challenges in planning therapy and prognostic uncertainties. Adjunctive treatment to antidepressants with cognitive-behavioral therapy (CBT) may be useful for these patients.
Practical guidance for prescribing trazodone extended-release in major depression. [2022]Treatment of major depressive disorder aims for symptom remission and recovery of function, and involves a multifaceted approach including drug therapy, evidence-based psychotherapy, and electroconvulsive therapy, according to disease severity. Antidepressant monotherapy is generally the first-line approach for moderate to severe major depressive disorder (with or without psychotherapy). In some severe cases, patients may require the addition of antipsychotic therapy, electroconvulsive therapy, or antidepressant combination therapy.