The Effect Of Transcranial Direct Current Stimulation In Panic Disorder

Study Overview
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Brief Summary
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The aim of the present study is to investigate the effect of prefrontal transcranial Direct Current Stimulation (tDCS) on clinical severity, attentional bias and interoceptive accuracy in panic disorder (PD). The participants will be assigned to active and sham groups (1:1) and will receive 10 sessions of tDCS. The study will also examine if the effects may last for a month.

Detailed Description
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Panic Disorder (PD) is one of the most common anxiety disorders. In spite of several available medications, there are unsatisfactory outcomes in a considerable proportion of PD patients and novel treatment approaches are lacking. Given that response to pharmacotherapeutical and psychological treatments occur after long intervals and medications may cause substantial adverse effects which may affect treatment compliance, fast acting and well-tolerated treatments such as non-invasive brain stimulation are considered to be useful as primary treatment approach or as an add-on treatment in PD. Repetitive Transcranial Magnetic Stimulation (rTMS) trials targeting prefrontal cortex mostly reported favorable outcomes in PD. Transcranial Direct Current Stimulation (tDCS) is another promising non-invasive brain stimulation method with numerous distinctive aspects including its low-cost, robust safety and tolerability, low dropout rates, easy application, reliable blinding procedures and the opportunity to use concomitantly with other treatments. Left anodal/right anodal tDCS over the dorsolateral prefrontal cortex has been demonstrated to decrease attentional bias and amygdala reactivity to threat in individuals with high trait anxiety. Moreover, a treatment-resistant case of PD was reported to have significant amelioration of symptoms up to one month after 10 sessions of tDCS. The study is a triple-blind randomized controlled trial. The sample will be consisted of thirty participants diagnosed as having PD due to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. The participants will be assigned to active or sham groups equally. Clinical severity will be assessed with adequate scales. Emotion recognition, attentional bias to threat and interoceptive accuracy will also be measured. Then, participants will be applied ten active or sham sessions of left anodal/right cathodal tDCS over the dorsolateral prefrontal cortex (DLPFC). All measurements will be repeated after the applications. Succinctly, the aim of this study is to assess the effect of ten sessions left anodal/right cathodal tDCS over the DLPFC on clinical severity, attentional bias and interoceptive accuracy in PD.

Official Title
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The Effect Of Prefrontal Transcranial Direct Current Stimulation On Clinical Severity, Attentional Bias and Interoceptive Accuracy In Panic Disorder

Conditions
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Panic Disorder

Intervention / Treatment
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* Device: Transcranial direct current stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a primary diagnosis of Panic Disorder, as confirmed by the Structured Clinical Interview for the DSM-5 (SCID-5); Patients currently on medication must be at the same stable dose(s) for one month prior to enrollment and be willing to continue at the same dose(s) through the duration of the study; Right-hand dominancy assessed by Edinburgh Handedness Inventory; Willingness and ability to comply with the requirements of the study protocol; Naïve to tDCS. 5 or more years of education Exclusion Criteria: Illiteracy, deficient language or refusal to participate or being not able to follow instructions or complete study tasks; Less than 5 years of education Individuals with any current or lifetime diagnosis of other Axis I disorders, as confirmed by the Structured Clinical Interview for the DSM-5 (SCID-5); History of substance or psychoactive compound use,with the exception of nicotine consumption; The presence of mental retardation diagnosis (previously identified) Individuals with a clinically defined neurological disorder, with an increased risk of seizure for any reason, with a history of treatment with rTMS, deep brain stimulation for any disorder will be excluded; Any personal or family history (1st degree relatives) of seizures other than febrile childhood seizures Personal history of head trauma that resulted in loss of consciousness for > 5 minutes and retrograde amnesia for > 30 minutes; Significant hearing loss or visual impairment; Diagnosis of any serious or uncontrolled medical condition such as chronic obstructive pulmonary disease, congestive heart failure or renal failure; Skin diseases that could potentially cause irritations under electrodes; Patients missing two consecutive protocol sessions; Patients with cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Group<br>Left anodal/right anodal transcranial direct current stimulation over the dorsolateral prefrontal cortex | Device: Transcranial direct current stimulation<br>* Participants will receive a total of 10 stimulation sessions. During each session, 2 milliAmpers of active or sham tDCS will be applied for 20 minutes over the dorsolateral prefrontal cortex (left anodal/right anodal).<br>* Other names: transcranial electrical stimulation;|
| Sham Comparator: Sham Group<br>Sham transcranial direct current stimulation over the dorsolateral prefrontal cortex | Device: Transcranial direct current stimulation<br>* Participants will receive a total of 10 stimulation sessions. During each session, 2 milliAmpers of active or sham tDCS will be applied for 20 minutes over the dorsolateral prefrontal cortex (left anodal/right anodal).<br>* Other names: transcranial electrical stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Panic Disorder Severity Scale (PDSS) scores | The PDSS consists of seven items, each rated on a 5-point scale, which ranges from 0 to 4. The items assess panic frequency, resulting distress, panic-focused anticipatory anxiety, phobic avoidance of situations and of physical sensations, impairment in occupational and social functioning. The overall assessment is made by a total score, which is calculated by summing the scores for all seven items. Minimum score is 0 and maximum score is 28. Higher scores indicate high levels of panic symptomatology. Reduction in score from baseline indicates clinical improvement of panic symptoms. | Up to one month | 
| Changes in Hamilton Anxiety Rating Scale (HAM-A) scores | The Hamilton Anxiety Rating Scale (HAM-A) is a multiple item questionnaire used to provide an indication of anxiety severity. Higher scores indicate high levels of symptomatology. Minimum score is 0 and maximum score is 56. Reduction in score from baseline indicates clinical symptom improvement. | Up to one month | 
| Changes in Clinical Global Impression-Severity (CGI-S) scores | Higher scores indicate the presence of high symptom severity. Decrease in scores from baseline reflects clinical symptom improvement. Minimum score is 1 and maximum score is 7. Patients will be classified as responders with a CGI-S = 1 or 2; and partial responders CGI-S = 3. | Up to one month | 
| Changes in performance on an attentional dot-probe task | Computerized dot-probe  attentional task will be used. Pairs of emotional faces (neutral/angry or neutral/happy) are randomly presented on a screen. Then, a probe is presented. Subjects are asked to indicate which side the probe approved and need to press the dot after the probe. Total time spent on Region of Interest (angry/neutral face) is measured. Attentional bias towards threat score is the subtraction of median reaction times (milliseconds) in congruent angry versus neutral trials from incongruent angry versus neutral trials. Minimum score is -1000 and maximum score is 1000. Positive scores indicate the presence of attentional vigilance towards threat whereas negative scores indicate an attentional avoidance towards threat. | Up to one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Hamilton Depression Rating Scale (HAM-D) scores | The Hamilton Depression Rating Scale (HAM-D) is a 17-item questionnaire used to provide an indication of depression severity. Minimum score is 0 and maximum score is 52. Higher scores indicate high levels of symptomatology. Reduction in score from baseline indicates clinical symptom improvement. | Up to one month | 
| Changes in Beck Depression Inventory (BDI) scores | The Beck Depression Inventory is a self-report questionnaire used to provide an indication of depression severity. Minimum score is 0 and maximum score is 63. Higher scores indicate high levels of symptomatology. Reduction in score from baseline indicates clinical symptom improvement. | Up to one month | 
| Changes in Sheehan Disability Scale (SDS) Work/School scores | The SDS Work/School is a single item measure rated on a 10-point scale. The SDS Work/School measures the extent to which work/school is impaired by symptoms. Minimum score is 0 and maximum score is 10, with higher scores reflecting greater impairment. | Up to one month | 
| Changes in Sheehan Disability Scale (SDS) Social Life scores | The SDS Social Life is a single item measure rated on a 10-point scale. The SDS Social Life measures the extent to which social life is impaired by symptoms. Minimum score is 0 and maximum score is 10, with higher scores reflecting greater impairment. | Up to one month | 
| Changes in Sheehan Disability Scale (SDS) Family Life/Home Responsibilities scores | The SDS Family Life/Home Responsibilities is a single item measure rated on a 10-point scale. The SDS Family Life/Home Responsibilities measures the extent to which family life/home responsibilities is impaired by symptoms. Minimum score is 0 and maximum score is 10, with higher scores reflecting greater impairment. | Up to one month | 
| Changes in Body Vigilance Scale (BVS) scores | BVS is designed to assess conscious attention focused on internal bodily sensations and perturbations. It is an 4-item likert type scale. Minimum score is 0 and maximum score is 40. Higher scores reflect greater body vigilance. | Up to one month | 
| Changes in Heartbeat Detection Accuracy | Heartbeat detection accuracy is an index ranging between 0 and 1 showing heart rate prediction performance. Higher scores reflect better interoceptive abilities. Heartbeat detection (interoceptive) accuracy is calculated by the following equation: 1/N ∑ (1 - (|recorded heartbeats - counted heartbeats|)/recorded heartbeats). N was the number of blocks for the heartbeat detection task. | Up to one month | 
| Changes in the number of correct responses at a facial expression recognition task | Participants are presented with individual pictures of facial expressions of emotions. Each presented face displays one of six basic emotions (anger, disgust, fear, happiness, sadness, or surprise). Each emotional expression is presented at different levels of intensity which have been created by combining shape and texture features of the two extremes neutral (0%) and full prototypical emotion (100%) to varying degrees. Participants are instructed to correctly classify each facial expression as angry, disgusted, fearful, happy, sad, surprised or neutral. Responses are made by pushing one out of six labelled keys on a response box. Hit rates and false alarm rates are measured separately for each emotion. Minimum accuracy percentage of an emotion is 0 and maximum accuracy percentage of an emotion is 100. Higher accuracy rates indicate better emotion recognition. | Up to one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anxiety disorders, Panic disorder, Transcranial Direct Current Stimulation, Interoceptive accuracy, Attention bias, Emotion recognition, Brain Stimulation