Predictors of Antidepressant Response
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Changes in Mu-opioid Binding Potential During PET
研究概览
简要总结
Major depression is a highly prevalent, frequently debilitating illness that too often fails to respond to currently available treatments such as antidepressant medication. Furthermore, randomized controlled trials of antidepressants consistently demonstrate large placebo effects. The investigators hypothesize that individual differences in the function of key brain circuits underlie the observed variability in clinical responses to both placebo and antidepressant medication. This study will test this hypothesis by recruiting treatment-seeking volunteers with major depression, with or without comorbid nicotine dependence. Volunteers will participate in positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans in the context of a treatment trial in which they will receive both placebo and antidepressant medication. A major goal of the study is to improve prediction of individual clinical responses in future treatment trials in which brain imaging may be unavailable, and to study the mechanisms of antidepressant response in Major Depression.
详细描述
We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either potentially "active" fast-acting antidepressant-like effects or to be "inactive") followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the µ-opioid receptor selective radiotracer [11C]carfentanil after each 1-week "inactive" and "active" oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmission under expectations of antidepressant effect.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria will include:
- •Participants diagnosed with Major Depressive Disorder and will include Hamilton Depressive Rating Scale (HDRS) scores >15
排除标准
- •Comorbid conditions that are medical, neurological or psychiatric, pregnancy, use of hormones (including birth control) or use of psychotropic agents
- •We will only permit certain past anxiety disorder diagnoses, including generalized anxiety, panic, agoraphobia, social phobia
- •We also will exclude left-handed individuals and patients who have used any centrally acting medications or recreational drugs with the past 2 months
- •No history of an implant, pacemaker or pacemaker wires, open heart surgery, artificial heart valve, brain aneurysm surgery, middle ear implant, hearing aid, braces or extensive dental work, cataract surgery or lens implant, implanted mechanical or electrical device, or artificial limb or joint
- •No metallic object in their body (such as braces) or have a history of foreign metallic object in the body such as bullets, BB's, pellets, shrapnel, or other metal fragments
研究组 & 干预措施
Known Placebo First
This arm gets a placebo that they know is a placebo (called inactive), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "active medication" (which is also actually a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa or alternative as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.
干预措施: Placebo, identified as placebo to participants (Other)
Known Placebo First
This arm gets a placebo that they know is a placebo (called inactive), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "active medication" (which is also actually a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa or alternative as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.
干预措施: Celexa or other antidepressant as clinically indicated (Drug)
Known Placebo First
This arm gets a placebo that they know is a placebo (called inactive), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "active medication" (which is also actually a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa or alternative as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.
干预措施: Placebo, identifed to participants as "Active medication" (Other)
"Active" (blinded) Placebo first group
This arm gets a placebo that they don't know is a placebo (called Active), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "inactive medication" (which participants know is a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.
干预措施: Placebo, identified as placebo to participants (Other)
"Active" (blinded) Placebo first group
This arm gets a placebo that they don't know is a placebo (called Active), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "inactive medication" (which participants know is a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.
干预措施: Celexa or other antidepressant as clinically indicated (Drug)
"Active" (blinded) Placebo first group
This arm gets a placebo that they don't know is a placebo (called Active), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "inactive medication" (which participants know is a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.
干预措施: Placebo, identifed to participants as "Active medication" (Other)
结局指标
主要结局
Changes in Mu-opioid Binding Potential During PET
时间窗: (90 minute PET scans) assessed at Weeks 1 and 2
Binding Potential = Bmax/Kd (receptor concentration/affinity). This is the most common measure of in vivo receptor binding with positron emission tomography. Whole brain changes in mu-opioid receptors binding potential during PET from the Inactive to the Active placebo condition. Positive numbers presented here represent reductions in binding potential from the inactive to the active condition.
Changes in BOLD Response During Reward fMRI Task (Monetary Incentive Delay, MID)
时间窗: (90 minute fMRI scans) assessed at Weeks 1 and 2
% BOLD signal changes in the nucleus accumbens from the Inactive to the Active Placebo condition.
次要结局
- Hamilton Depression Rating Scale Scores(Screening, week 0, week 2, week 4, week 8 and week 10)
- Changes From Baseline in Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) Score(From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention))
- Changes in Dopamine (D 2/3) Binding Potential During PET.((90 minute PET scan) assessed at Weeks 1 and 2)
- Changes From Baseline in PHQ-9 Depression Scores.(From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention))
- Montgomery-Asberg Depression Rating Scale(Screening, week 0, week 2, week 4, week 8 and week 10)
研究者
Jon-Kar Zubieta
MD PhD
University of Michigan