tDCS and Psychotherapy for the Treatment of Anxiety Disorders

Study Overview
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Brief Summary
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The main goal of the study is to test the efficacy of tDCS in combination with the Unified Protocol for transdiagnostic treatment of emotional disorders, to reduce anxiety symptoms in a mixed anxiety disorders sample, as assessed by the Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959).

Detailed Description
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Participants will be randomly allocated to one of four parallel experimental arms, within a 2X2 factorial design in which two interventions (tDCS and CBT-UP) will be delivered, and assessed according to two levels (e.g., intervention vs. no intervention). Each study participant will assigned to one factor level. Four intervention groups are defined active tDCS + CBT-UP sham tDCS + CBT-UP active tDCS + Psychoeducation sham tDCS + Psychoeducation The four arms allow to experimentally control the two active therapeutic interventions: active tDCS and CBT-UP. Sham tDCS is the control for active tDCS and psychoeducation is the control condition for CBT-UP. The intervention will last for 15 weeks, and all groups will comply with the same intervention structure according to the examination plan established in the protocol: week 1-2: 1 CBT-UP session/week week 3-4: 5 tDCS sessions and 1 CBT-UP session/week week 5-8: 2 tDCS sessions and 1 CBT-UP session/week week 9-14: 1 tDCS session and 1 CBT-UP session/week week 15: 1 CBT-UP session The treatment will consist of 26 transcranial direct current stimulation sessions, each lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle. tDCS will be combined with cognitive-behavioral therapy, in particular following the unified protocol for transdiagnostic treatment of emotional disorders (Barlow et al. 2018). Safety: No serious adverse effects are expected with conventional tDCS protocols in humans (≤40 min, ≤4 mA; conclusions from a meta-analysis observing >33200 sessions, >1000 subjects with repeated sessions; Bikson et al., 2016). Plans for treatment or care after the subject has ended his/her participation in the trial: Patients will be recommended and offered the best treatment as evidenced by the trial results. For patients that already completed that intervention further standard psychological/psychiatric treatment will be recommended according to patients' status.

Official Title
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The Efficacy of Transcranial Direct Current Stimulation Combined With the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: a Double Blind, Sham Controlled, Randomized Factorial Designed Study for Anxiety Disorders

Conditions
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Anxiety Disorders

Intervention / Treatment
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* Device: active tDCS
* Device: sham tDCS
* Behavioral: CBT-UP
* Behavioral: Psychoeducation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of generalized anxiety disorder, specific phobia, panic disorder, agoraphobia, or social anxiety disorder. Willing to participate and to give written informed consent Exclusion Criteria: Contra-indications to tDCS use: Presence of a cardiac or neurological condition Metallic implants If contact with scalp is not possible Have had a head injury resulting in a loss of consciousness that has required further investigation History of seizures Epilepsy or a history of epilepsy Past adverse effects with non-invasive stimulation treatments Current diagnosis of another psychiatric disorder (except for depression, as long as secondary diagnosis), psychoactive medication or psychological treatment Left-handedness Pregnancy Skin condition on the stimulation target area Recreational drug use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active tDCS + CBT-UP<br>Active tDCS combined with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders. | Device: active tDCS<br>* 26 transcranial direct current stimulation sessions, each lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle.<br>* Other names: Transcranial Direct Current Stimulation;Behavioral: CBT-UP<br>* 15 psychotherapy sessions (1/week) following the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders developed by Barlow et al. 2018.<br>|
| Active Comparator: sham tDCS + CBT-UP<br>Sham tDCS (control for active tDCS) combined with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders. | Device: sham tDCS<br>* tDCS is controlled in this intervention: sham mode.<br>Behavioral: CBT-UP<br>* 15 psychotherapy sessions (1/week) following the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders developed by Barlow et al. 2018.<br>|
| Active Comparator: active tDCS + Psychoeducation<br>Active tDCS combined with psychoeducation (control condition for CBT-UP). | Device: active tDCS<br>* 26 transcranial direct current stimulation sessions, each lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle.<br>* Other names: Transcranial Direct Current Stimulation;Behavioral: Psychoeducation<br>* To control for the cognitive-behavioral intervention we will use psychoeducation materials.<br>|
| Placebo Comparator: sham tDCS + Psychoeducation<br>Sham tDCS combined with psychoeducation (control conditions for active tDCS and CBT-UP). | Device: sham tDCS<br>* tDCS is controlled in this intervention: sham mode.<br>Behavioral: Psychoeducation<br>* To control for the cognitive-behavioral intervention we will use psychoeducation materials.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) | The mean change in the Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) score, from baseline. HARS total score ranges from 0 to 56, where higher values indicate higher anxiety symptom's severity. | At week 8th, 15th (middle and end of treatment) and 6 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment | Defined as reduction of total Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) score by ≥ 50%. | At week 8th, 15th (middle and end of treatment) and 6 months follow-up. | 
| Remission to treatment | Defined as reduction of total Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) to scores lower than 18 (indicating mild anxiety severity). | At week 8th, 15th (middle and end of treatment) and 6 months follow-up. | 
| Hamilton Depression Rating Scale (HRSD; Hamilton, 1960) | The mean change in the Hamilton Depression Rating Scale (HRSD; Hamilton, 1960) score, from baseline. HDRS total score ranges from 0 to 75, where higher values indicate higher depressive symptoms' severity. | At week 8th, 15th (middle and end of treatment) and 6 months follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anxiety disorders, tDCS, Unified Protocol, RCT