Clinical Research Directory

Transdiagnostic Metacognitive Therapy Compared to Disorder-Specific Cognitive-Behavioral Therapy for Anxiety Disorders

Background Anxiety disorders are the most prevalent psychiatric disorders around the world. Effective treatment consists of pharmacotherapy or psychological treatment based on cognitive-behavioral therapy (CBT) and these treatment options are recommended in clinical guidelines, with CBT as the first-line treatment for anxiety disorders. However, only 50% of patients with anxiety disorders achieve remission status following CBT and 20% of patients drop out of CBT. Metacognitive therapy (MCT) represents an alternative treatment approach to CBT. The theoretical model of MCT emphasizes the role of dysfunctional metacognitions (rather than cognitions, as in CBT), particularly negative metacognitions, in the development and maintenance of anxiety disorders and other psychiatric disorders. Metacognitions refer to cognitions about cognition, for example, a belief such as "When I start worrying, I cannot stop". Several meta-analyses indicate that MCT may be superior to CBT for various psychiatric disorders. However, more studies with larger samples are required to draw firm conclusions about the effectiveness of MCT. An alternative approach to disorder-specific treatment is transdiagnostic treatment; that is, the application of a single, generic protocol for several disorders. There are advantages of transdiagnostic treatments in comparison to disorder-specific treatments in terms of therapist learnability (i.e., easier to learn one protocol than several) and dissemination into routine care. Despite the MCT model being described as applicable to a range of psychiatric disorders and MCT as a potentially transdiagnostic approach, at present there is only one sufficiently large study that compared transdiagnostic MCT (tMCT) to disorder-specific CBT. Purpose and aims The purpose of the present project is to investigate the effectiveness of tMCT compared to disorder-specific CBT in patients with anxiety disorders in psychiatric care and evaluate the cost-effectiveness. Aim 1 is to compare the short- and long-term effects of tMCT and CBT, from pre- to post-assessment and from post-assessment to 6- and 12-month follow-up assessments. Aim 2 is to examine possible mediators of change (metacognitions and cognitions). Aim 3 is to compare the cost-effectiveness of tMCT to CBT. Design and setting The project has a prospective, pragmatic, two-arm parallel-group randomized controlled superiority trial design and is conducted in psychiatric services in Stockholm, Sweden. Treatment is conducted in an individual format and face-to-face. Randomization and blinding Each participant is stratified individually on principal diagnosis prior to randomization and then randomly allocated with a 1:1 ratio to tMCT or CBT. A list of random numbers is generated for each diagnosis for each psychiatric unit by an individual independent of the project. Researchers, therapists, participants, and independent assessors are blinded to the allocation sequence. Assessors are also blinded to treatment condition at post-treatment assessment. Researchers are blinded to treatment allocation in the analysis phase at all assessment points. Therapist training and supervision Therapists are licensed psychologists or psychotherapists with prior training in CBT and employed in psychiatric services in Stockholm, Sweden. Only therapists who can show competence in MCT and CBT, respectively, are allowed to treat participants in the project. Procedure Patients are consecutively assessed for eligibility by project therapists. As part of routine clinical care, patients are assessed for principal and comorbid diagnoses. Patients meeting criteria for GAD, SAD, or PTSD are assessed whether they meet other inclusion but not exclusion criteria for participation in the project. Patients provide written informed consent to therapists. At pre-treatment, participants complete outcome measures. Participants are then randomly assigned to tMCT or CBT. Following the last session, and at 6-month and 12-month follow-up assessments, participants complete the same measures as at pre-treatment. In addition, at post-treatment principal and comorbid diagnoses are assessed by independent assessors. Data analysis Multilevel modeling is used to estimate between-group effects on outcome measures from pre- to post-assessment (following treatment completion; primary endpoint), and from post-assessment to 6- and 12-month follow-up assessments. To be comparable across diagnoses, scores on the primary outcome of disorder-specific measures are standardized by calculating z-scores. Missing data are estimated using maximum likelihood estimation. Data from all randomized participants are used in the multilevel models, following the principle of intention-to-treat. A detailed study protocol has been submitted for publication.

LHC-CIDI-5 in Hong Kong

The World Health Organization Composite International Diagnostic Interview-5th (CIDI-5) is a standardized diagnostic tool used to assess the prevalence of mental and substance use disorders over varying time frames (30 days, 12 months, and lifetime) based on the diagnostic criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) and International Classification of Diseases 10th edition (ICD-10). However, retrospective measurements like the CIDI-5 are susceptible to recall bias, especially for the lifetime experience, which can hinder the reporting accuracy with mental disorders. To mitigate this issue, the life history calendar (LHC) was introduced as an aid to assist respondents in recalling the timing of life events, enhancing the ability of the CIDI-5 to measure the lifetime prevalence of mental disorders. The LHC is a grid structure with columns representing time units and rows representing life domains under study. In a study conducted in Nepal, combining the CIDI-5 with the LHC resulted in a significant increase in the detection of mental disorders compared to using the CIDI-5 alone. This approach did not lead to an increase in false positives after clinical validation. This experiment aims to adapt a Hong Kong version of the LHC based on the Nepalese model and evaluate the effectiveness of the LHC-assisted CIDI-5 (LHC-CIDI-5) compared to the CIDI-5 alone in assessing mental disorders.

Cannabidiol-Assisted Learning for Managing Generalized Anxiety Disorder

This randomized, double-blind, placebo-controlled clinical trial investigates the use of Food and Drug Administration (FDA)-approved cannabidiol (EPIDIOLEX®) as an adjunct to cognitive behavioral therapy (CBT) in adults with generalized anxiety disorder (GAD). The study aims to evaluate whether cannabidiol-assisted CBT enhances emotion regulation via dorsomedial prefrontal cortex (dmPFC) activation and improves anxiety symptom outcomes compared to CBT with placebo.

Stepped Care Treatment for Anxiety Resilience

Childhood anxiety disorders (CAD) are common and impairing. Family based cognitive behavioral therapy (CBT) is efficacious in treating CAD. Yet, many children do not receive care due to barriers such as limited provider availably, high treatment costs, and constrained family resources (e.g., time). To combat these barriers, other treatment methods have been developed. The stepped care treatment models maximize resources by providing low-intensity, low-cost interventions as a first time treatment, while stepping up care for those needing more intensive treatment. Specifically, a stepped care model for CAD that begins with a parent-focus intervention has great promise to deliver efficacious and cost-effective treatment without having to engage the child. While stepped care approaches show promise in treating CAD with comparable efficacy to standard CBT, there remains a large research-to-practice gap. The stepped care model for CAD that begins with a parent-focused intervention has yet been explored, and very little is known about intervention mediators that explain mechanisms of change. This research is being done to improve the reach and quality of services using a stepped care model, offering an affordable and practical solution to the widespread gap in youth mental health care.

Personalized AI-Driven Models in Cognitive Behavioral Therapy for Anxiety

Untreated anxiety undermines long-term physical and emotional wellbeing, especially among college students, with rates worsening since the onset of the COVID-19 pandemic. Cognitive Behavioral Therapy (CBT) is the leading evidence-based intervention for anxiety, but many students fail to complete exercises between CBT sessions, reducing its effectiveness. Socially assistive robots (SARs) help promote adherence to home-based practice in the context of elder care, social skill learning, and physical therapy, but it is unknown how SARs can enhance CBT. The specific objective of this research is to develop personalized CBT SARs that can support CBT compliance for college students with anxiety. To meet the goals of the proposed work, these studies will determine how SAR personalization based on implicit and explicit feedback can help promote greater CBT compliance and anxiety reduction outcomes for students.

Transcranial Alternating Current Stimulation for Generalized Anxiety Disorder and Insomnia: An Open-Label Pilot Study

This is an open-label pilot clinical trial to evaluate the effects of transcranial alternating current stimulation (tACS) in adults diagnosed with generalized anxiety disorder (GAD) and chronic primary insomnia. The study will involve 30 participants who will receive 20 sessions of tACS over four weeks. The stimulation will be delivered at 15 mA and 77.5 Hz using the Nexalin device. The main goal is to assess improvements in anxiety and sleep quality. Results from this study will provide preliminary evidence for future randomized controlled trials.

Text Message Safety Behavior Fading for Pathological Worry

The current study aims to explore the efficacy of a text message-based Safety Behavior Fading Intervention compared to a PMR control condition.

Study to Assess Adverse Events and Change in Disease Activity When Oral ABBV-932 is Added to Antidepressant Therapies in Adult Participants With Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is usually treated with antidepressant therapy (ADT); however, sometimes ADTs alone are not enough to adequately treat GAD. The purpose of this study is to assess how safe and effective ABBV-932 is when added to the antidepressant therapies in adult participants with GAD who have had an inadequate response ADTs. ABBV-932 is an investigational drug being developed for the adjunctive treatment of GAD. Participants will be randomly assigned to receive ABBV-932 or Placebo in addition to their currently prescribed ADTs. There is 1 in 3 chance of participants assigned to Placebo. Approximately 315 adult participants with GAD and inadequate response to ADTs will be enrolled in approximately 50 sites in the United States and Puerto Rico. Participants will receive oral capsules of ABBV-932 or matching placebo in addition to their prescribed ADT for 6 weeks and then will be followed for an additional 4 week follow-up period. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

An Examination of the Performance of QbMobile in Differential Diagnosis Associated With ADHD Symptoms

The purpose of this study is to evaluate QbMobile's ability to collect objective data to identify specific symptom profiles in differential diagnoses (ASD, MDD, Bipolar Disorder and Anxiety Disorder) that are common with ADHD.

Therapy and Tech Study

The investigators want to test if gen AI can support therapy by recruiting patients already in therapy.

The Effect of Patient Preference for Treatment Model in Internet Delivered Cognitive Behavior Therapy for Generalized Anxiety Disorder

The goal of this clinical trial is to investigate the effect of allowing patients to choose between two internet-based cognitive behavioral treatments (ICBT) for generalized anxiety disorder (GAD). The goal is also to examine psychologists' ability to predict which of the two treatments the patient will benefit most from. The main questions it aims to answer are: * Do patients who are randomized to choose their treatment improve more in their GAD symptoms compared to patients who are randomly assigned to a treatment? * Does allowing patients to choose their treatment increase treatment adherence, compared to being randomly assigned to a treatment? * Does allowing patients to choose their treatment increase treatment satisfaction and credibility, compared to being randomly assigned to a treatment? * Does allowing patients to choose their treatment increase patients' sense of agency related to the treatment process, compared to being randomly assigned to a treatment? * Do patients who receive a treatment that matches the psychologist's prediction of which treatment would fit the patient best show better treatment outcomes (primarily reduction in GAD symptoms over time, but also secondary outcomes such as satisfaction), compared to patients who receive a treatment that does not match the psychologist's prediction? Participants included in the trial will be randomized to one of two conditions: 1) read short descriptions of the two treatment programs and based on that choose the preferred treatment, 2) randomly being allocated to one of the two treatments. The two internet-based treatment programs which the patients can choose between or be randomly allocated to are: 1) Intolerance of uncertainty-based ICBT and 2) Metacognition-based ICBT. Both programs consist of 8 treatment modules and run for 10 weeks. Patients in both conditions receive continuous support by a psychologist through a built-in message function on the treatment platform. The patient will receive feedback from the psychologist on their assignments and exercises and the psychologist will respond to the participants' messages.

Internet-Based Cognitive Behavioral Therapy With Treatment as Usual for Generalized Anxiety Disorder and Major Depressive Disorder in Taiwan (ICBT-TW)

This study aims to evaluate the effectiveness of internet-based cognitive behavioral therapy (ICBT) combined with treatment as usual (TAU) for adults diagnosed with generalized anxiety disorder (GAD) or major depressive disorder (MDD) in Taiwan. CBT is a proven treatment for anxiety and depression, but traditional face-to-face sessions require frequent clinic visits, which may be costly and time-consuming. ICBT delivers similar therapy content online, allowing participants to complete sessions at their own pace, reducing barriers such as travel and scheduling. A total of 160 participants will be randomly assigned to receive either TAU alone or TAU plus an 8-week ICBT program delivered via a secure national research platform. The program includes 12 online modules covering cognitive restructuring, emotion regulation, and behavioral activation techniques. Participants will complete assessments before, during, and after the program, with follow-up at 3 months. The results will help determine whether ICBT can improve symptoms, enhance treatment accessibility, and support the integration of digital mental health interventions into clinical practice in Taiwan.

Comparative Effectiveness of Internet-based Versus Parent-Coached Cognitive-Behavioral Therapy For Children and Adolescents With Anxiety and OCD

Anxiety disorders in children and adolescents are common and confer significant disability. Cognitive behavioral therapy (CBT) is the recommended treatment for youth with anxiety, yet many families cannot access CBT due to cost, practicalities of attending in-person treatment sessions, and a shortage of trained providers, especially in rural areas. To combat these barriers, other treatment methods have been developed. Previous research has shown that family-based, internet-delivered CBT (iCBT) for anxiety and OCD in youth has shown a significant reduction in anxiety symptoms. Parent-coached exposure therapy (PCET) focuses entirely on teaching parents and youth together how to address anxiety through the completion of in-session parent-coached exposures and assigning parent-coached exposure as homework in between sessions. Although both iCBT and PCET show positive results in treating pediatric anxiety in comparison to standard-care CBT, little is known about the comparative efficacy of iCBT and PCET. This research is being done to understand the comparative effectiveness of two different types of cognitive-behavioral therapy (CBT) for treating anxiety or OCD in youth.

Metacognitive Therapy vs Unified Protocol for Patients With Comorbid Anxiety Disorders

The primary goal of this randomized controlled trial is to compare the effectiveness of two transdiagnostic psychological treatments, Metacognitive Therapy (MCT) and the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP), for patients with complex anxiety.

Safety, Tolerability, and Preliminary Efficacy of Psilocybin Oral Solution in Adults With Generalized Anxiety Disorder

This Phase 2a clinical trial is designed to evaluate the safety, tolerability, and preliminary efficacy of a 3 mg dose of psilocybin oral solution for the treatment of Generalized Anxiety Disorder (GAD). The study consists of three sequential phases: Screening Phase (up to 4 weeks), Open-label Run-in Phase (4 weeks), Double-blind Treatment Phase (4 weeks) Screening Phase During the Screening Visit, participants will provide informed consent and undergo a comprehensive medical evaluation, including an abbreviated psychiatric assessment, to determine eligibility. To qualify, patients must have a clinician-rated Hamilton Anxiety Rating Scale (HAM-A) score ≥14. Additionally, participants must not be on regular anxiolytic treatment or must have discontinued such treatment at least 4 weeks prior to the start of the Open-label Run-in Phase. Open-label Run-in Phase Eligible patients will proceed to the 4-week Open-label Run-in Phase. During this phase, patients will attend four weekly clinic visits, supplemented by weekly remote contacts (via phone or email). At different timepoints during the OL Run-in Phase, participants will complete safety assessments, undergo cognitive testing and EEG and other patient reported outcomes (PROs). Double-blind Treatment Phase Participants who demonstrate a treatment response during the Open-label Phase-defined as a ≥50% reduction in GAD-7 score from baseline-will be randomized 1:1 to receive either psilocybin oral solution or placebo at the Double-blind Baseline Visit. Patients not meeting the response criteria will undergo End-of-Treatment (ET) procedures at this visit. At different timepoints during the DB Treatment Phase, participants will complete safety assessments, undergo cognitive testing and EEG and other patient reported outcomes (PROs). Completion of the End of Treatment (ET) phase will be 2 weeks to further assess safety and PROs.

Relief From Stress Via Social Protection in Senegal

Despite the growing prevalence of mental health disorders in low- and middle-income countries, significant barriers to seeking and accessing mental health services persist. Within lower income populations, the prevalence of mental health disorders and barriers to addressing them are worsened by poverty. Self-Help Plus is a group-based stress management program delivered using a task-sharing model and designed to circumvent barriers to addressing mental health concerns. Cultural adaptations of Self-Help Plus have been implemented in several countries and are considered cost-effective. However, to date, Self-Help Plus has not been adapted for Senegalese populations. The study detailed in this manuscript aims to assess the feasibility and acceptability of Self-Help Plus in lower income populations in Senegal. The study is a pilot feasibility cluster-randomized control trial of Self-Help Plus in four Senegalese communities. Clusters of social protection program beneficiaries will be randomly selected to receive five sessions of Self-Help Plus. The intervention will be delivered in groups of up to 30 beneficiaries and co-facilitated by two community workers. A combination of quantitative and qualitative research methods will be used to assess the feasibility and acceptability of both the Self-Help Plus intervention and randomized control trial procedures. The study sample will include social protection program beneficiaries in the treatment and control groups, Self-Help Plus facilitators, project staff supporting the training of facilitators, and the intervention supervisor. The findings of this study will be used to inform the potential integration of Self-Help Plus and/or similar mental health interventions into the national social protection program in Senegal.

Targeting Social Function in Anxiety and Eating Disorders

Social processing and cognition are often altered in patients with eating disorders. The goal of this clinical trial is to assess two different social therapeutic interventions -- one educational, one interactive -- for their effectiveness in improving clinical outcomes in patients with eating disorders. Patients in both interventions will receive education about social function in eating disorders, but those in the interactive treatment group will complete an additional collaborative art task. Participants will: * attend a baseline study visit to complete clinical interviews, cognitive testing, and behavioral tasks * complete a pre-intervention assessment with questionnaires * attend eight sessions of their assigned treatment group over the course of 12 weeks * complete three virtual follow-up assessments 4, 8, and 12 months from their baseline * attend a final study visit to repeat some clinical interviews, cognitive testing, and behavioral tasks Researchers will compare changes in eating disorder, mood, and anxiety symptoms as well as test results from baseline and final study visits for each group to see if * patients can be treated effectively with education alone or if an interactive group component produces additional benefits * cognitive and behavioral task performance are associated with recovery or illness state.

Clinical Efficacy and Mechanism of rTMS Based on dlPFC in the Intervention of Generalized Anxiety Disorder With Insomnia

To investigate the intervention effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on insomnia symptoms of generalized anxiety disorder patients.

Assess the Utility of a Speech-based Machine Learning Algorithm to Predict Treatment Response to Psychiatric Interventions

This is a research study looking at whether the way people speak can help predict how well they'll respond to certain mental health treatments. The Main Goal: The researchers want to see if computer analysis of a person's speech patterns can predict whether they'll respond well to two specific treatments: TMS (Transcranial Magnetic Stimulation) and Spravato (a nasal spray medication). They're focusing on people with depression, bipolar disorder, OCD, anxiety, and PTSD. How It Works: 200 people with these conditions will participate in the study.Participants will record themselves speaking for about 12 minutes, responding to six different prompts.They'll do these recordings before treatment starts, daily during treatment, right after treatment ends, and again four weeks later. Doctors will track how well people are doing using various questionnaires and rating scales The researchers will look for connections between speech patterns and treatment success. The study will last 12 months. What Makes Someone a "Treatment Success": The study considers treatment successful if a person's symptoms improve significantly (specifically, a 2-point or greater reduction on a clinical rating scale (called Clinical Global Impression) and stays improved during the follow-up period (4-weeks). Why This Matters: If successful, this research could lead to a simple, non-invasive way to help doctors predict which treatments might work best for different patients. This could help people get the most effective treatment more quickly and help healthcare providers use their resources more efficiently. Safety Consideration The researchers will also check whether doing the speech assessments causes any distress to participants, making sure the evaluation process itself is safe and comfortable.

EEG Study on Neurophysiological and Psychological Effects of Ericksonian Hypnotherapy in Generalized Anxiety Disorder

This study examines the neurophysiological and psychological effects of Ericksonian hypnotherapy in individuals diagnosed with Generalized Anxiety Disorder (GAD). Using electroencephalography (EEG), the study aims to assess changes in brain activity and anxiety symptoms before and after treatment. A total of 60 participants will be recruited from both governmental and private psychiatric clinics in Istanbul. Participants will be randomly assigned to either the intervention group (receiving 12 Ericksonian hypnotherapy sessions over 12 weeks) or the control group (receiving no intervention). The primary outcome measures include changes in EEG patterns, specifically alpha, theta, and frontal asymmetry indices, and changes in anxiety severity, measured by the Beck Anxiety Inventory (BAI), Generalized Anxiety Disorder-7 (GAD-7), and State-Trait Anxiety Inventory (STAI). Secondary measures include emotional regulation (DERS) and quality of life (WHOQOL-BREF). This study aims to provide scientific evidence on the effectiveness of Ericksonian hypnotherapy as a complementary treatment for GAD and its impact on brain function and emotional well-being.

Therapeutic Effect of Neuromodulation on Anxiety Disorders by High-Definition Transcranial Electrical Stimulation

High-definition transcranial electrical stimulation (HD-tES) is a non-invasive brain neuromodulation technique that applies a small electrical current to the scalp to alter neural excitability and stimulate localized brain activation. Previous clinical trials have explored the use of HD-tES for treating mental health conditions such as depression, anxiety, obsessive-compulsive disorder, and post-traumatic stress disorder. This trial aims to investigate the efficacy and safety of HD-tES in ameliorating anxiety symptoms among patients with generalized anxiety disorder (GAD), thereby validating its potential as a treatment for anxiety disorders. Participants will be randomly assigned to one of four HD-tES treatment groups: (1) HD-tES inhibitory waveform (cDC+cTBS) applied to the right dorsolateral prefrontal cortex (DLPFC) for 10 minutes, followed by sham excitatory waveform (aDC+iTBS) stimulation applied to the left DLPFC for 10 minutes. (2) Sham inhibitory waveform (cDC+cTBS) stimulation applied to the right DLPFC for 10 minutes, followed by HD-tES excitatory waveform (aDC+iTBS) applied to the left DLPFC for 10 minutes. (3) HD-tES inhibitory waveform (cDC+cTBS) applied to the right DLPFC for 10 minutes, followed by HD-tES excitatory waveform (aDC+iTBS) applied to the left DLPFC for 10 minutes. (4) Sham inhibitory waveform (cDC+cTBS) stimulation applied to the right DLPFC for 10 minutes, followed by sham excitatory waveform (aDC+iTBS) stimulation applied to the left DLPFC for 10 minutes. Regardless of the group assignment, participants will undergo treatment sessions over a 2-week period, with five sessions per week and no more than one session per day. Each session lasts approximately 20 minutes. Assessments will be conducted before the treatment, weekly during the treatment period (at the end of the first and second weeks), and a follow-up evaluation will be performed one week after the conclusion of the treatment.