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.
试验速览
- 阶段
- 不适用
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Change in Montgomery-Asberg Depression Rating Scale (MADRS) at week 3.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Allocation masking will be done through sequentially numbered cards that will determine which group each patient will belong to. The card determines whether the coil to be used will produce actual or simulated stimulation. A secretary who does not participate directly in the research will be responsible for handling the numbered cards to the patient prior to each session. Participants and staff will not fully know the status of allocation groups.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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).
研究组 & 干预措施
Active TBS Arm
Patients randomized to this arm will receive active TBS 5 consecutive days of the week (Monday to Friday) in the first 3 weeks and then 2 alternate days of the week (with interval of at least 1 day between sessions) for another 3 weeks.
干预措施: Active Theta Burst Stimulation (TBS) (Device)
Sham TBS Arm
Patients randomized to this arm will receive sham TBS 5 consecutive days of the week (Monday to Friday) in the first 3 weeks and then 2 alternate days of the week (with interval of at least 1 day between sessions) for another 3 weeks.
干预措施: Sham Theta Burst Stimulation (TBS) (Device)
结局指标
主要结局
Change in Montgomery-Asberg Depression Rating Scale (MADRS) at week 3.
时间窗: From baseline until 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.
次要结局
- Remission rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.(From baseline until week 6.)
- Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) at week 6.(From baseline until week 6.)
- Response rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 3(From baseline until week 3.)
- Remission rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 3(From baseline until week 3.)
- Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) at week 3.(From baseline until week 3.)
- Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) at week 6.(From baseline until week 6.)
- Change in Barratt Impulsivity Scale of 11 items (BIS-11) at week 6.(From baseline until week 6.)
- Change in Global Assessment of Functioning (GAF) Scale at week 3.(From baseline until week 3.)
- Change in Global Assessment of Functioning (GAF) Scale at week 6.(From baseline until week 6.)
- Response rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.(From baseline until week 6.)
- Change in Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.(From baseline until week 6.)
- Change in Young Mania Rating Scale (YMRS) at week 3.(From baseline until week 3.)
- Change in Young Mania Rating Scale (YMRS) at week 6.(From baseline until week 6.)
- Change in Hamilton Anxiety Scale (HAM-A scale) at week 3.(From baseline until week 3.)
- Change in Hamilton Anxiety Scale (HAM-A scale) at week 6.(From baseline until week 6.)
- Change in Global Clinical Impression Scale of Severity (GCI-S) at week 3.(From baseline until week 3.)
- Change in Global Clinical Impression Scale of Severity (GCI-S) at week 6.(From baseline until week 6.)
- Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) at week 3.(From baseline until week 3.)
- Change in Barratt Impulsivity Scale of 11 items (BIS-11) at week 3.(From baseline until week 3.)
- Frequency of adverse events in UKU-SERS Scale at week 6.(From baseline until week 6.)
研究者
Ricardo Alberto Moreno, M.D., Ph.D.
Principal investigator
University of Sao Paulo