DECIDE- Deep Phenotyping for Clinical Inferring Response in Treatment Resistant Depression -Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- multimodal and multivariate signature to predict outcome of lithium augmentation
研究概览
简要总结
DECIDE- Deep phenotyping for clinical inferring response in treatment resistant depression -Study
Building upon the "Biobanking" initiative at the Max Planck Institute of Psychiatry, the present project aims to identify clinically relevant subtypes of treatment-resistant depression (TRD) through Clinical Deep Phenotyping (CDP). According to clinical trials, 30-40% of the patients suffering from TRD benefit from lithium treatment. By collecting multimodal biological and clinical-diagnostic markers, such as structural and functional brain imaging via magnetic resonance imaging (MRI), brain signals from electroencephalography, comprehensive blood tests, assessment of perception and cognition through neuropsychological testing, as well as the evaluation of specific depression symptoms and psychological and other comorbidities using standardized questionnaires, a bio-clinical signature will be identified using multivariate machine learning algorithms as an integration method. This signature aims to predict the response to lithium therapy in TRD. Prospectively, such an algorithm could later personalize the treatment decision of 'lithium administration in TRD'. This concept is in line with the Research Domain Criteria (RDoC) of the National Institute of Mental Health (NIH) and aims to offer lithium therapy as a personalized treatment strategy for TRD. Specifically, this means that the likelihood of treatment response can be estimated before administration based on the results of the present study, thus enabling lithium to be offered specifically to those patients who are likely to benefit from it. The study design is non-interventional, meaning the decision for lithium treatment is made for patients according to clinical routine in accordance with the recommendation of the German National Treatment Guideline (NVL) independent of study enrollment. Study participation does not influence treatment decisions for the patients.
详细描述
DECIDE- Deep phenotyping for clinical inferring response in treatment resistant depression -Study
Background:
TRD is a form of major depressive disorder (MDD) typically characterized by an inadequate response (partial or no response) to first-line antidepressants (AD) therapy of adequate dose and duration. This variant of depression, common in psychiatry, affects approximately 30-50% of all patients with depression and is the focus of the present DECIDE-study. In treating TRD, augmenting existing antidepressant pharmacotherapy with lithium proves to be an effective option, recommended in the German national care guideline. The precise definition of TRD within this study encompasses the following criteria and is based on Bauer et al. 2013:
- Confirmation of MDD diagnosis according to DSM-V, verified through the Mini Neuropsychiatric Interview (MINI)-Interview.
- Inadequate response to treatment after ≥4 weeks of antidepressant (AD) therapy. Inadequate response is defined as not achieving remission from depressive symptoms following ≥28 days of AD usage prior to the study. This determination includes the exclusion of pseudo-resistance through measurement of medication plasma levels.
- Stage I TRD is characterized by the failure of ≥1 adequate trial using one major class of AD. Major classes are selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic and tetracyclic antidepressants (TCAs), Monoamine oxidase inhibitors (MAOIs) and atypical antidepressants.
- Stage II TRD is characterized by the failure of two distinct classes of major AD. A Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥25 serves as an additional qualifying criterion.
Importantly, while only around 30% patients experience benefits after 4 to 6 weeks of lithium treatment, those who do respond often experience significant relief. In the NVL, it is recommended to assess the effectiveness of lithium therapy after 2-4 weeks. If the patient does not benefit, lithium should be discontinued. However, despite substantial benefits by the recommended lithium application in clinical use, the augmentation strategy of lithium in TRD faces limitations in clinical practice due to concerns by physicians about lithium's potential side effects. Therefore, there is a risk that the use of lithium treatment in TRD remains under-exploited despite evidence for its significant potential to aid patients with TRD. Having a predictive tool indicating lithium efficacy in specific TRD patients before therapy initiation could aid psychiatrists in deciding to pursue lithium treatment.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Obligated Participation in "Biobanking" of Max Planck Institute of psychiatry
- •Age: ≥18 years
- •DSM-V diagnosis of major depressive disorder (MDD; confirmed by Mini-Interview)
- •Treatment resistant depression (TRD): TRD stage I or TRD stage II
- •Indication for antidepressant pharmacotherapy
- •Indication for lithium augmentation
- •Ability to provide informed consent
排除标准
- •Age: < 18 years
- •Medical conditions incompatible with lithium therapy
- •History of hypomanic or manic episode
- •Two or more antidepressant substances simultaneously to lithium, except the combination with sleep-promoting antidepressants like Mirtazapine, Mianserin, or Trazodone
- •An alternative pharmacological augmentation strategy simultaneously to lithium disorder
- •Quetiapine immediate- and extended release more than 100 mg in total
- •Current substance use disorder except for moderate alcohol or benzodiazepine use bound to the current episode, or smoking
- •Patients who are not suitable for the study in the opinion of the investigator
- •Patients with a relevant comorbidity of the central nervous system such as focal neurological disease (stroke, tumour), current or past epilepsy, CNS inflammation including autoimmune disease, traumatic brain injury, past brain surgery
- •Patients that are not able to provide informed consent
- •Electroconvulsive therapy (ECT) in the current depressive episode
- •Repetitive transcranial magnetic stimulation (rTMS) in the current depressive episode
结局指标
主要结局
multimodal and multivariate signature to predict outcome of lithium augmentation
时间窗: Timepoint: Baseline (Inclusion into study)
Sensitivity and specificity of a multimodal and multivariate signature to predict outcome of lithium augmentation in TRD
次要结局
- Global improvement in Clinical Global Impression Score measured by the proportion of patients with an Improvement of much or very much improved (Clinican rating)(Timepoint: Baseline (Inclusion into study), Follow up 2-6 (week 2 after an effective lithium level was achieved, week 3, week 4, week 5, week 6) and Outcome (between week 3 to 6 - dependent on patients' course of disease))
- Change in suicidality measured by the assessment of the Columbia-Suicide Severity Rating Scale (C-SSRS) between timepoints(Timepoint: Baseline (Inclusion into study), Outcome (between week 3 to 6 - dependent on patients' course of disease))
- Amount of Lithium Side effects using Lithium Side Effects Rating Scale(Timepoint: Baseline (Inclusion into study), Follow up 2-6 (week 2 after an effective lithium level was achieved, week 3, week 4, week 5, week 6) and Outcome (between week 3 to 6 - dependent on patients' course of disease))
- Clinician rated Remission rate defined as a Montgomery Asberg Depression Scale total score ≤10 Montgomery Asberg Depression Scale(Timepoint: Baseline (Inclusion into study), Follow up 2, 4, 6, 7 (week 2 after an effective lithium level was achieved, week 4, week 6, week 52) and Outcome (between week 3 to 6 - dependent on patients' course of disease))
- Change of global functioning measured by the Global Assessment of Functioning Scale (clinician rating)(Timepoint: Baseline (Inclusion into study), Follow up 2-6 (week 2 after an effective lithium level was achieved, week 3, week 4, week 5, week 6) and Outcome (between week 3 to 6 - dependent on patients' course of disease))
- Change of depressive symptoms measured by the Patient Health Questionnaire 9 (self-rating)(Timepoint: Baseline (Inclusion into study), Follow up 2-6 (week 2 after an effective lithium level was achieved, week 3, week 4, week 5, week 6) and Outcome (between week 3 to 6 - dependent on patients' course of disease))
- Clinician rated Response rate defined as a proportion with ≥ 50% reduction in baseline Montgomery Asberg Depression Scale(Timepoint: Baseline (Inclusion into study), Follow up 2, 4, 6, 7 (week 2 after an effective lithium level was achieved, week 4, week 6, week 52) and Outcome (between week 3 to 6 - dependent on patients' course of disease))
- Total score change in the Becks Depression Inventory, version 2 (self-rating)(Timepoint: Baseline (Inclusion into study), Outcome (between week 3 to 6 - dependent on patients' course of disease))
- Improvement of psychosocial and occupational functioning measured by the Health-related quality of life (WHOQOL-BREF, self-rating)(Timepoint: Baseline (Inclusion into study), Outcome (between week 3 to 6 - dependent on patients' course of disease))