Neurobiological and Genomic Predictors of Relapse After Discontinuation of Antidepressant Treatment in Major Depressive Disorder: An Observational Prospective Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 204
- 试验地点
- 1
- 主要终点
- Relapse rate
研究概览
简要总结
The goal of this observational study is to test whether the discontinuation of antidepressant medications for patients with depression can be decided after the normalization of biological parameters. The main questions it aims are:
- When patients with depression treated with antidepressants, does their brain activity also become normal? If so,
- Then, can we stop the antidepressant treatment and expect minimum repeat of depression?
The participants who receive a specific antidepressant treatment will be asked to:
- Undergo quantitative electroencephalography (qEEG),
- Record Event-related potential (ERP),
- Record Sleep EEG
- Answer Hamilton Depression Rating Scale question their psychiatrists asked
- Give blood sample for genetic analysis
- Repeat the above mentioned procedures for at least 3 times during their treatment period.
Researchers will compare the results of patients with the results of healthy controls.
详细描述
When Should Antidepressant Treatment Be Discontinued? A Prospective Healthy-Controlled Case-Control Study
Background First-line treatments for Major Depressive Disorder (MDD) include second-generation antidepressants-such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)-and/or evidence-based psychotherapies (American Psychological Association, 2019). While the efficacy of antidepressants in preventing relapse is well-established, approximately 40% of patients experience recurrence after discontinuing treatment (Kato et al., 2021). Due to the lack of clear guidelines on optimal treatment duration, some have suggested lifelong maintenance therapy. However, despite their relatively low side-effect profile, long-term antidepressant use is often reported as distressing by up to half of patients (Cascade et al., 2009).
Therefore, it is essential to identify predictive markers that can guide clinicians in deciding when it is safe to discontinue medication without increasing the risk of relapse. A recent meta-analysis conducted by our group found that demographic and clinical variables such as age, sex, or treatment resistance failed to predict recurrence (Arikan et al., 2023). Consequently, the focus has shifted to biological, electrophysiological, and genetic markers.
Objective The primary purpose (objective) of this study is to investigate whether various biological indicators provide sufficient metrics for discontinuing treatment in patients diagnosed with Major Depressive Disorder (MDD).
Study Design
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
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
- 是
入选标准
- •Outpatients
- •For patients, satisfying Major Depressive Disorder for Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR)
- •Drug-free for at least 1-week
排除标准
- •Any neurological and psychiatric comorbid conditions
- •Hearing loss
- •Physical diseases
研究组 & 干预措施
Depression-Relapsed Prospectively Followed
This cohort includes patients whose long-term outcome is unknown at the start of the study. They are enrolled, treated, and monitored over time. At the study's conclusion, they will be retrospectively categorized as "Relapsers".
干预措施: Antidepressant Medications (Drug)
Recurrent Depression Retrospectively Defined
Group A (Retrospective / Known Phenotype): This group consists of patients with a confirmed history of recurrent depression. Recurrence defined as no relapse within 1 year after discontinuation of medication. Data for this group is collected at a single time point (Baseline/T0).
干预措施: Antidepressant Medications (Drug)
Depression-Non-Relapsers Prospectively Followed
This cohort includes patients whose long-term outcome is unknown at the start of the study. They are enrolled, treated, and monitored over time. At the study's conclusion, they will be retrospectively "Non-Relapsers" (in Remission).
干预措施: Antidepressant Medications (Drug)
Healthy Control
This group is composed of individuals with no history of psychiatric illness. Data is collected at a single time point to establish a healthy baseline for all biomarkers.
Non-Recurrent Depression Retrospectively Defined
This group consists of patients with a confirmed history of a single depressive episode or no relapse within 1 year after discontinuation of medication. Data for this group is collected at a single time point (Baseline/T0).
结局指标
主要结局
Relapse rate
时间窗: From the discontinuation of antidepressant treatment to the first relapse within 6-12 months.
The number of person relapsed, which is evaluated by Hamilton Depression Rating Scale, after discontinuation of antidepressant treatment.
次要结局
- Severity of Depression - Baseline (T0)(Baseline - T0: Before the start of antidepressant medication.)
- Severity of Depression - Treatment Response (T1)(T1: 4-8 weeks after the start of antidepressant treatment (T0))
- Severity of Depression - End of Treatment (T2)(T2: 6-12 months after the start of antidepressant medication(T0).)
- Severity of Depression - End of Study (T3)(T3: 6-12 months after the discontinuation of treatment(T2))
- QEEG absolute power- Baseline (T0)(Baseline (Day 0) - T0 (Patients): Before the start of antidepressant medication. Baseline (Day 0) - T0 (Controls): For the control group, this assessment is conducted at the end of initial psychiatric evaluation to establish baseline measurements.)
- QEEG absolute power at Treatment Response (T1)(T1: 4-8 weeks after the start of antidepressant treatment (T0))
- QEEG absolute power - End of Treatment (T2)(T2: 6-12 months after the start of treatment (T0))
- QEEG absolute power - Last Relapse Control - End of the Study (T3)(T3: 6-12 months after the discontinuation of treatment(T2))
- P300 amplitude - Baseline (T0)(Baseline (Day 0) - T0 (Patients): Before the start of antidepressant medication. Baseline (Day 0) - T0 (Controls): For the control group, this assessment is conducted at the end of initial psychiatric evaluation to establish baseline measurements.)
- P300 amplitude at Treatment Response (T1)(T1: 4-8 weeks after the start of antidepressant treatment (T0))
- P300 amplitude- End of Treatment (T2)(T2: 6-12 months after the start of treatment (T0))
- P300 amplitude- Last Relapse Control - End of the Study (T3)(T3: 6-12 months after the discontinuation of treatment(T2))
- REM latency - Baseline (T0)(Baseline (Day 0) - T0 (Patients): Before the start of antidepressant medication. Baseline (Day 0) - T0 (Controls): For the control group, this assessment is conducted at the end of initial psychiatric evaluation to establish baseline measurements.)
- REM latency - End of Treatment (T2)(T2: 6-12 months after the start of treatment (T0))
- REM Latency Last Relapse Control - End of the Study (T3)(T3: 6-12 months after the end of treatment (T2))
- DNA Genome Analysis - Baseline (T0)(Baseline (Day 0) - T0 (Patients): Before the start of antidepressant medication. Baseline (Day 0) - T0 (Controls): For the control group, this assessment is conducted at the end of initial psychiatric evaluation to establish baseline measurements.)
- RNA Sequencing - Baseline (T0)(Baseline (Day 0) - T0 (Patients): Before the start of antidepressant medication. Baseline (Day 0) - T0 (Controls): For the control group, this assessment is conducted at the end of initial psychiatric evaluation to establish baseline measurements.)
- RNA Sequencing - End of Treatment (T2)(T2: 6-12 months after the start of antidepressant treatment (T0))
- RNA Sequencing - End of Study (T3)(T3: 6-12 months after the end of treatment (T2))
- Micro RNA Sequencing - Baseline (T0)(Baseline (Day 0) - T0 (Patients): Before the start of antidepressant medication. Baseline (Day 0) - T0 (Controls): For the control group, this assessment is conducted at the end of initial psychiatric evaluation to establish baseline measurements.)
- Micro RNA Sequencing - End of Treatment (T2)(T2: 6-12 months after the start of antidepressant treatment (T0))
- Micro RNA Sequencing - End of Study (T3)(T3: 6-12 months after the end of treatment (T2))
- DNA Methylation - Baseline (T0)(Baseline (Day 0) - T0 (Patients): Before the start of antidepressant medication. Baseline (Day 0) - T0 (Controls): For the control group, this assessment is conducted at the end of initial psychiatric evaluation to establish baseline measurements.)
- DNA Methylation - End of Treatment (T2)(T2: 6-12 months after the start of antidepressant treatment (T0))
- DNA Methylation - End of Study (T3)(T3: 6-12 months after the end of treatment (T2))
- DNA Length - Baseline (T0)(Baseline (Day 0) - T0 (Patients): Before the start of antidepressant medication. Baseline (Day 0) - T0 (Controls): For the control group, this assessment is conducted at the end of initial psychiatric evaluation to establish baseline measurements.)
- DNA Length - End of Treatment (T2)(T2: 6-12 months after the start of antidepressant treatment (T0))
- DNA Length - End of Study (T3)(T3: 6-12 months after the end of treatment (T2))
研究者
Mehmet Kemal Arikan
Professor Doctor
Uskudar University