Clinical trial NCT04123301: Theta-Burst Stimulation in Major Depressive Episodes With Mixed Characteristics.
Official title: Theta-Burst Stimulation (TBS) in Major Depressive Episodes With Mixed Characteristics in Bipolar and Major Depressive Disorder: a Randomized, Controlled, Double-blind, Parallel-group Clinical Trial of Efficacy, Safety, and Tolerability.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Depressive Episode
Depressive Disorder
Bipolar Disorder
Keywords: mixed depression
depressive disorder
bipolar disorder
transcranial magnetic stimulation
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2019-10-10
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, parallel-group, 6-week, sham-controlled clinical trial.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) at week 3.
timeFrame: From baseline until week 3.
Secondary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
timeFrame: From baseline until week 6.
measure: Change in Young Mania Rating Scale (YMRS) at week 3.
timeFrame: From baseline until week 3.
measure: Change in Young Mania Rating Scale (YMRS) at week 6.
timeFrame: From baseline until week 6.
measure: Response rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 3
timeFrame: From baseline until week 3.
measure: Response rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
timeFrame: From baseline until week 6.
measure: Remission rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 3
timeFrame: From baseline until week 3.
measure: Remission rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
timeFrame: From baseline until week 6.
measure: Change in Hamilton Anxiety Scale (HAM-A scale) at week 3.
timeFrame: From baseline until week 3.
measure: Change in Hamilton Anxiety Scale (HAM-A scale) at week 6.
timeFrame: From baseline until week 6.
measure: Change in Global Clinical Impression Scale of Severity (GCI-S) at week 3.
timeFrame: From baseline until week 3.
measure: Change in Global Clinical Impression Scale of Severity (GCI-S) at week 6.
timeFrame: From baseline until week 6.
measure: Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) at week 3.
timeFrame: From baseline until week 3.
measure: Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) at week 6.
timeFrame: From baseline until week 6.
measure: Change in Global Assessment of Functioning (GAF) Scale at week 3.
timeFrame: From baseline until week 3.
measure: Change in Global Assessment of Functioning (GAF) Scale at week 6.
timeFrame: From baseline until week 6.
measure: Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) at week 3.
timeFrame: From baseline until week 3.
measure: Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) at week 6.
timeFrame: From baseline until week 6.
measure: Change in Barratt Impulsivity Scale of 11 items (BIS-11) at week 3.
timeFrame: From baseline until week 3.
measure: Change in Barratt Impulsivity Scale of 11 items (BIS-11) at week 6.
timeFrame: From baseline until week 6.
measure: Frequency of adverse events in UKU-SERS Scale at week 6.
timeFrame: From baseline until week 6.
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Institute of Psychiatry, University of Sao Paulo
Study officials:
affiliation: University of Sao Paulo
name: Ricardo Moreno, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tavares DF, Suen P, Rodrigues Dos Santos CG, Moreno DH, Lane Valiengo LDC, Klein I, Borrione L, Marques Forte P, Brunoni AR, Alberto Moreno R. Treatment of mixed depression with theta-burst stimulation (TBS): results from a double-blind, randomized, sham-controlled clinical trial. Neuropsychopharmacology. 2021 Dec;46(13):2257-2265. doi: 10.1038/s41386-021-01080-9. Epub 2021 Jun 30.
citation: Tavares DF, Dos Santos CGR, Valiengo LDCL, Klein I, Borrione L, Forte PM, Brunoni AR, Moreno RA. Efficacy, Safety, and Tolerability of Theta-Burst Stimulation in Mixed Depression: Design, Rationale, and Objectives of a Randomized, Double-Blinded, Sham-Controlled Trial. Front Psychiatry. 2020 May 15;11:435. doi: 10.3389/fpsyt.2020.00435. eCollection 2020.