The Use of Methylphenidate to Improve Clinical Outcomes in Geriatric Depression: A Double-blind Placebo-Controlled Trial of Methylphenidate (Ritalin) Augmentation of Citalopram (Celexa) in Depressed Elderly Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 181
- 试验地点
- 1
- 主要终点
- Hamilton Depression Rating Scale (HDRS) Maintained Scores at Week 16
研究概览
简要总结
This study will evaluate the safety and effectiveness of methylphenidate in improving cognition and function in older adults with depression.
详细描述
Less than 50% of older adults with depression achieve remission and functional recovery in response to first-line antidepressant treatment. Most are left with significant residual symptoms, putting them at risk for illness relapse, frailty, and suicide. Improved understanding of the neurobiology of depression in older adults and mechanisms of treatment response may lead to better clinical management of depression. Methylphenidate (MPH) has long been used in the elderly and the medically ill to provide rapid improvement in depression, apathy, and fatigue. However, its potential beneficial effects on cognitive and functional outcomes in older adults with depression have not been studied. Combining MPH with the serotonergic antidepressant citalopram may result in better clinical outcomes than would using citalopram alone. This study will compare the safety and effectiveness of MPH combined with citalopram, MPH combined with placebo, and citalopram combined with placebo in improving thinking, memory, and speed of recovery in older adults with depression. The study will also evaluate selected dopamine- and serotonin-related gene relationships with mood, cognitive symptoms, and treatment response to MPH and citalopram.
Participation in this double-blind study will last 16 weeks. All potential participants will initially undergo comprehensive medical, neuropsychiatric, and cognitive assessments and genetic testing. These initial assessments will include questionnaires about depressive symptoms, a medical history, an electrocardiogram (ECG), and a blood draw for the genetic testing. Eligible participants will then be randomly assigned to one of three groups: MPH and citalopram, MPH and placebo, or citalopram and placebo. All participants will receive 16 weeks of treatment with their assigned medications. Study visits will occur weekly for the first 6 weeks of treatment and bi-weekly for the remainder of the study. During study visits, participants will undergo vital sign and weight measurements, answer questionnaires, and report any medication side effects. Blood will again be drawn at Visits 4 and 10, and the ECG will be repeated at Visit 10 if any cardiac symptoms occur. Most initial assessments will be repeated on Visit 13, the last study visit. Participants will also be contacted weekly by phone throughout the study to answer questions on how they are feeling and any possible side effects.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for major depressive disorder (recurrent and nonrecurrent course will be identified)
- •Score of 16 or higher on the 24-item Hamilton Depression Rating Scale (HDRS) at study entry
- •Score of 26 or higher on the Mini-Mental State Exam (MMSE)
排除标准
- •History of psychiatric illness or a substance abuse disorder other than unipolar depression, diagnosed prior to the onset of the first depressive episode
- •Presence of psychotic symptoms
- •Severe or acute medical illness (e.g., major surgery, metastatic cancer, stroke, heart attack) 6 months prior to study entry
- •Acute suicidal or violent behavior or history of suicide attempt within the year prior to study entry
- •Presence of delirium, neurodegenerative dementia, Parkinson's disease, or any other central nervous system (CNS) diseases
- •Toxic or metabolic abnormalities on laboratory examination
- •Medications taken or medical illnesses present that could account for depression
- •Active heart failure categorized as Class III or greater according to New York Heart Association criteria
- •Heart attack or crescendo angina within the 3 months prior to study entry
- •Symptomatic cardiac arrhythmias or symptomatic, hemodynamically significant mitral or aortic valvular disease
- •Resting heart rate less than 50 beats per minute and a corrected QT (QTc) interval greater than 0.45 seconds
- •Second or third degree atrioventricular block
- •Systolic blood pressure greater than 180 mmHg or less than 90 mmHg and diastolic blood pressure greater than 105 mmHg or less than 50 mmHg at study entry
- •Treated with depot neuroleptic therapy within 6 months prior to study entry
- •Treated with any neuroleptic, antidepressant, anxiolytic medication (other than lorazepam), or over-the-counter CNS-active medications used for treatment of depression (e.g, St. John's Wort, kava-kava, melatonin) within 2 weeks (4 weeks for fluoxetine or monoamine-oxidase inhibitors (MAOIs)) prior to the first administration of study medication
- •Known allergy to citalopram or MPH or history of ineffective treatment with citalopram or MPH for current depressive episode
- •Requires concomitant therapy with any prescription or over-the-counter medications that have potentially dangerous interactions with either citalopram or MPH
- •Requires electroconvulsive therapy (ECT) or received ECT within 3 months prior to study entry
- •Initiated psychotherapy within 3 months prior to study entry or will be initiating or terminating psychotherapy during the study
研究组 & 干预措施
1 - Citalopram and placebo
Participants will take a combination of citalopram and placebo for 16 weeks
干预措施: Citalopram (Drug)
1 - Citalopram and placebo
Participants will take a combination of citalopram and placebo for 16 weeks
干预措施: Placebo (Drug)
2 - Methylphenidate and placebo
Participants will take a combination of methylphenidate and placebo for 16 weeks
干预措施: Methylphenidate (MPH) (Drug)
2 - Methylphenidate and placebo
Participants will take a combination of methylphenidate and placebo for 16 weeks
干预措施: Placebo (Drug)
3 - Methylphenidate and Citalopram
Participants will take a combination of methylphenidate and citalopram for 16 weeks
干预措施: Citalopram (Drug)
3 - Methylphenidate and Citalopram
Participants will take a combination of methylphenidate and citalopram for 16 weeks
干预措施: Methylphenidate (MPH) (Drug)
结局指标
主要结局
Hamilton Depression Rating Scale (HDRS) Maintained Scores at Week 16
时间窗: Maintained response measured at Week 16
The Hamilton Depression Rating Scale (HDRS) is a 24-item depression scale and the total score is summed with a minimum score=0 and maximum score=76. There are no subscales and the higher values represent a worse outcome. Outcomes are measured and defined as follows: 1) Response will be defined as HDRS scores of 10 or less; 2) Sustained response will be defined as maintained response at week 16; 4) Remission will be defined as HDRS scores of 6 or less.
次要结局
- Quality of Life Assessment(Measured at Baseline and Week 16)
研究者
Helen Lavretsky, MD
Professor
University of California, Los Angeles