Transcranial Direct Current Stimulation for the Treatment of Bipolar Depression

Study Overview
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Brief Summary
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Non-invasive brain stimulation therapies have been increasingly investigated in recent years as a treatment for neuropsychiatric disorders, particularly mood disorders. They are particularly appealing since many patients are either refractory or present side effects to standard pharmacological regimens. TDCS (transcranial direct current stimulation). a novel non- pharmacological brain stimulation technique, might help in overcoming some of these issues, since it has low cost, high portability and it is relatively easy to use. TDCS consists in applying a weak, direct current through two electrodes placed over the scalp; the anode and the cathode increasing and decreasing cortical excitability during and beyond the period of stimulation. It is also a safe technique with only mild adverse effects described. Previous studies, some of them from our group, have described that tDCS is an effective technique for major depression. However, the role of tDCS as a treatment for bipolar depression (BD) has been insufficiently investigated. Therefore, our aim is to address the antidepressant effects of tDCS in BD in a randomized, sham- controlled trial in a refractory sample.

Detailed Description
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BD represents the greatest burden on patients with bipolar disorder, since the depressive episodes are the most frequent and also particularly associated with suicide 7. BD treatment is controversial, with some stricter guidelines recommending only lithium, lamotrigine and quetiapine as a first-treatment, whereas others allow the use of antidepressants (which can increase manic switch and should be used in association with mood stabilizers) and other anticonvulsants and antipsychotics 8. For refractory BD the available level I evidence is very scarce, with only seven studies exploring this issue hitherto 9. Therefore, the importance of this study proposal is justified considering the burden of the disease, the paucity of current therapeutic studies and the promising results presented for tDCS in unipolar disorder.

Official Title
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Transcranial Direct Current Stimulation for the Treatment of Bipolar Depression

Conditions
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Depression, Bipolar

Intervention / Treatment
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* Device: Sham stimulation
* Device: Active stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: bipolar depressed (type I, II or not otherwise specified) participants with symptoms in spite of an adequate treatment course with mood stabilizers. the depressive episode has to be of at least moderate intensity (baseline HDRS>=16) read and understand Portuguese Exclusion Criteria: other neuropsychiatric conditions, such as schizophrenia, substance dependence, dementias, traumatic brain injury, epilepsy and so forth (although participants with anxiety disorders can be included whether the primary diagnosis is BDD); mixed states, defined as simultaneously presenting (hypo)manic symptoms with a Young Manic Rating Scale (YMRS) > 8; pregnancy; specific contra-indications to tDCS; severe/life-threatening clinical conditions. Participants will have to be drug-free or at stable drug regimen for at least 6 weeks prior to trial onset. Benzodiazepine drugs will be allowed, although only at low doses (less than 20mg/day of diazepam or equivalent).

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active stimulation<br>Active stimulation (tDCS) will be used in the dose of 2mA /30 min per day, for 10 days and two extra sessions every other week (total of 12 sessions). | Device: Active stimulation<br>* For active tDCS, we will place the anode and the cathode over the left and right dorsolateral prefrontal cortex areas, respectively (corresponding to F3 and F4 according to the EEG 10-20 system). We will use 5x5 cm electrodes and a 2mA current for 30 minutes per day. This montage is known as bifrontal setup and has been previously used in major depression trials<br>|
| Placebo Comparator: Sham stimulation<br>For Sham Transcranial Direct Current Stimulation, the device is automatically turned off after 30 seconds of stimulation and remains turned off. | Device: Sham stimulation<br>* For sham tDCS, the device will be turned off after 30 seconds of stimulation.<br>* Other names: TDCS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Scale for Depression, 17 items | Continuous measure (score change) | week 0 (baseline), week 2, week 4 and week 6 (endpoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Asberg Depression Rating Scale | Continuous measure (score changes) | week 0 (baseline), week 2, week 4 and week 6 (endpoint) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar disorder, depression, transcranial direct current stimulation, non invasive brain stimulation