The investigators will perform a double-blind, randomized, sham-controlled clinical trial of theta-burst stimulation (TBS) in mixed depressive episodes of both bipolar and major depressive disorders. Will be selected 90 patients aged 18-65 years with diagnosis of TB (I or II) or MDD in moderate or severe major depressive episode with mixed features. The primary endpoint of efficacy will be a continuous outcome of change in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to week 3.
INTRODUCTION: Mixed-specifier mood disorders are probably a different subgroup in terms of response to treatment, socio-demographic parameters, course and family history. The investigators will perform a clinical trial of theta-burst stimulation (TBS) in mixed depressive episodes of both bipolar (I and II) and major depressive disorders. METHODS: The study is designed as a randomized, sham-controlled, double-blinded clinical trial evaluating TBS for the treatment of moderate or severe major depressive episodes with mixed features of patients receiving at least one first or second line pharmacological treatment for depressive episodes without adequate response. Ninety adult (18 to 65 yo) patients will be enrolled and submitted to 6-week (comprising 5 consecutive days a week sessions for the first 3 weeks and then 2 days a week for a further 3 week) of inhibitory followed by excitatory TBS in dorsolateral prefrontal cortex. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in Montgomery-Asberg Depression Scale (MADRS) score over time and across groups. Cognitive parameters will also be assessed with neuropsychological tests.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
90
Each session will be comprised of ACTIVE TBS: first, continuous inhibitory stimulation (cTBS) in the right dorsolateral prefrontal cortex followed by intermittent excitatory stimulation (iTBS) in the left dorsolateral prefrontal cortex.
The sham-TBS sessions will be performed using an identical coil that produces SHAM Stimulation: first, sham continuous inhibitory stimulation (cTBS) in the right dorsolateral prefrontal cortex followed by sham intermittent excitatory stimulation (iTBS) in the left dorsolateral prefrontal cortex.
Institute of Psychiatry, University of Sao Paulo
São Paulo, Brazil
RECRUITINGChange in Montgomery-Asberg Depression Rating Scale (MADRS) at week 3.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 3.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
Change in Young Mania Rating Scale (YMRS) at week 3.
Change in Young Mania Rating Scale (YMRS) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 13-19 - hypomania; 20-25 - mild mania; 26-37 - moderate mania ; 38-60 - severe mania. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 3.
Change in Young Mania Rating Scale (YMRS) at week 6.
Change in Young Mania Rating Scale (YMRS) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 13-19 - hypomania; 20-25 - mild mania; 26-37 - moderate mania ; 38-60 - severe mania. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
Response rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 3
Reduction of 50% or more of the Montgomery-Asberg Depression Rating Scale (MADRS) in each patient in both interventional groups. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 3.
Response rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
Reduction of 50% or more of the Montgomery-Asberg Depression Rating Scale (MADRS) in each patient in both interventional groups. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
Remission rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 3
Montgomery-Asberg Depression Rating Scale (MADRS) \< 11 points in each patient in both interventional groups. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 3.
Remission rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
Montgomery-Asberg Depression Rating Scale (MADRS) \< 11 points in each patient in both interventional groups. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
Change in Hamilton Anxiety Scale (HAM-A scale) at week 3.
Change in Hamilton Anxiety Scale (HAM-A scale) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 0-17 - mild anxiety; 18-24 moderate anxiety; 25-30 - severe anxiety. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 3.
Change in Hamilton Anxiety Scale (HAM-A scale) at week 6.
Change in Hamilton Anxiety Scale (HAM-A scale) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 0-17 - mild anxiety; 18-24 moderate anxiety; 25-30 - severe anxiety. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
Change in Global Clinical Impression Scale of Severity (GCI-S) at week 3.
Change in Global Clinical Impression Scale of Severity (GCI-S) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 1- not sick; 2- very mild disease; 3- mild disease; 4- moderate disease; 5- intense disease; 6- severe disease; 7- extremely severe disease. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 3.
Change in Global Clinical Impression Scale of Severity (GCI-S) at week 6.
Change in Global Clinical Impression Scale of Severity (GCI-S) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 1- not sick; 2- very mild disease; 3- mild disease; 4- moderate disease; 5- intense disease; 6- severe disease; 7- extremely severe disease. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) at week 3.
Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) in both interventional groups.The scale range is: 26 to 130 points. Increase is a better and reduction is a worse outcome.
Time frame: From baseline until week 3.
Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) at week 6.
Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) in both interventional groups.The scale range is: 26 to 130 points. Increase is a better and reduction is a worse outcome.
Time frame: From baseline until week 6.
Change in Global Assessment of Functioning (GAF) Scale at week 3.
Change in Global Assessment of Functioning (GAF) Scale in both interventional groups. The scale range is: 1 to 100 points. Increase is a better and reduction is a worse outcome.
Time frame: From baseline until week 3.
Change in Global Assessment of Functioning (GAF) Scale at week 6.
Change in Global Assessment of Functioning (GAF) Scale in both interventional groups. The scale range is: 1 to 100 points. Increase is a better and reduction is a worse outcome.
Time frame: From baseline until week 6.
Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) at week 3.
Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) in both interventional groups. The scale range is: 18 to 72 points. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 3.
Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) at week 6.
Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) in both interventional groups. The scale range is: 18 to 72 points. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
Change in Barratt Impulsivity Scale of 11 items (BIS-11) at week 3.
Change in Barratt Impulsivity Scale of 11 items (BIS-11) in both interventional groups. The scale range is: 30 to 120 points. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 3.
Change in Barratt Impulsivity Scale of 11 items (BIS-11) at week 6.
Change in Barratt Impulsivity Scale of 11 items (BIS-11) in both interventional groups. The scale range is: 30 to 120 points. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
Frequency of adverse events in UKU-SERS Scale at week 6.
Frequency of adverse events in UKU-SERS Scale in both interventional groups.The scale range is: 0 to 57 points. Reduction is a better and increase is a worse outcome.
Time frame: From baseline until week 6.
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