Theta-Burst Stimulation in Major Depressive Episodes With Mixed Characteristics.
Theta-Burst Stimulation in Major Depressive Episodes With Mixed Characteristics.
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.
Inclusion Criteria:

 -  Current mixed depression in any mood disorder (bipolar I, bipolar II or major
 depressive disorder) assessed with Montgomery-Asberg Depression Rating Scale (MADRS)
 score ≥ 20 points AND Young Mania Rating Scale (YMRS) score ≥ 1 point in 3 or more
 items.

 -  Any appropriate first or second line pharmacological regimen in accordance with CANMAT
 guidelines to treat a major depressive episode in major depressive disorder
 (Agomelatina 25-50 mg/dia; Bupropiona 150-300 mg/dia; Citalopram 20-40 mg/dia;
 Desvenlafaxina 50 - 100 mg/dia; Duloxetina 60 - 120mg/dia; Escitalopram 10 - 20
 mg/dia; Fluoxetina 20 - 60 mg/dia; Fluvoxamina 100 - 300 mg/dia; Mirtazapina 15 - 45
 mg/dia; Paroxetina 20 - 60 mg/dia; Sertralina 50 - 200 mg/dia; Venlafaxina 75 - 225
 mg/dia; Vortioxetina 10 - 20 mg/dia; Amitriptilina 150 - 300 mg/dia; Imipramina 150 -
 300 mg/dia; Clomipramina 150 - 200 mg/dia; Nortriptilina 75 - 150 mg/dia; Trazodona
 150 - 300 mg/dia; Quetiapina 150 - 300mg/dia), bipolar I (Quetiapina 300 - 600 mg/dia;
 Lítio litemia 0,6 - 1,2 mEq/L; Lamotrigina 100 - 200 mg/dia; Lurasidona 40 - 80
 mg/dia; Lítio/Divalproato + Lurasidona; Lítio/Divalproato + Lamotrigina; Olanzapina 5
 - 20 mg/dia + Fluoxetina 20 - 60 mg/dia; Divalproato de sódio; Lítio/Divalproato +
 ISRS/Bupropiona) or bipolar II disorder (Quetiapina 300 - 600 mg/dia; Lítio;
 Lamotrigina; Bupropiona; Sertralina; Venlafaxina).

 Exclusion Criteria:

 -  Concomitant diagnosis of other neuropsychiatric disorders such as: schizophrenia,
 dementias, mental retardation, organic mental disorder, or epilepsy;

 -  Acute suicide ideation (assessed by interview and clinical evaluation);

 -  Suspected or confirmed pregnancy;

 -  Women in breastfeeding;

 -  Severe or unstable clinical disease;

 -  Specific contraindications to TBS: previous epileptic seizures; change in
 electroencephalogram at some point in life; previous stroke; previous severe TBI (with
 neurosurgery); metallic object on head (except mouth) as projectile piece, surgical
 clip, welding fragments; any implanted device (cardiac pacemaker, intravenous
 catheter).