Methylphenidate Use to Improve Outcomes in Geriatric Depression

哌醋甲酯用于改善老年抑郁症的预后

• 批准号: 8015572
• 负责人: Helen Lavretsky
• 金额: $ 34.3万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015572
• 关键词: Acute; Address; Admission activity; Adverse effects; Advertising; Affective Symptoms; African American; Age; Aging; Ambulatory Care; Ambulatory Care Facilities; Antidepressive Agents; Asians; Attention Concentration; Behavior; Behavioral; Brain; Candidate Disease Gene; Caregivers; Case Study; Chronic; Citalopram; Clinic; Clinical; Clinical Management; Code; Cognitive; Collaborations; Communities; Consent Forms; Consultations; Controlled Clinical Trials; County; County Hospitals; DRD4 gene; Data; Dementia; Depressed mood; Development; Diabetes Mellitus; Diagnosis; Disease; Disease remission; Dopamine; Dopamine Receptor; Dopaminergic Agents; Double-Blind Method; Dropout; Elderly; Enrollment; Ethnic Origin; European; Family member; Feeling suicidal; Freedom; Functional disorder; Gene Frequency; Gene Structure; Genes; Genetic; Genetic Polymorphism; Genetic screening method; Genomics; Genotype; Geriatric Psychiatry; HTR2A gene; Hamilton Rating Scale for Depression; Haplotypes; Healthcare; Heritability; Hispanics; Hospitalization; Hospitals; Housing; Impaired cognition; Impairment; Individual; International; Intervention; Latino; Lead; Left; Light; Literature; Los Angeles; Major Depressive Disorder; Medical; Mental Depression; Mental Health; Methodology; Methylphenidate; Minority; Monitor; Moods; Morbidity - disease rate; Motivation; Nature; Neurobehavioral Manifestations; Neurobiology; Newspapers; Nucleotides; Olives - dietary; Outcome; Outcome Assessment; Participant; Pathway interactions; Patient Recruitments; Patient Self-Report; Patients; Pattern; Performance; Personal Satisfaction; Pharmacogenomics; Pharmacotherapy; Pilot Projects; Placebo Control; Placebos; Population; Principal Investigator; Probability; Psychiatrist; Published Comment; Race; Randomized; Receptor Gene; Recommendation; Recovery of Function; Recruitment Activity; Regulation; Relapse; Relative (related person); Reporting; Research; Research Design; Research Personnel; Research Subjects; Residual state; Resources; Review Literature; Risk; Role; Sampling; Serotonin; Serotonin Agents; Severities; Site; Source; Stratification; Stress; Study Subject; Suicide; Surgeon; Symptoms; Syndrome; System; Testing; Therapeutic Studies; Time; Training; Utah; Visit; Withdrawal; Woman; Work; alertness; base; chronic depression; cognitive function; cognitive impairment no dementia; depressive symptoms; design; disability; dopamine transporter; executive function; follow-up; frailty; functional disability; geriatric depression; health disparity; improved; insight; instrumental activity of daily living; interest; lectures; medical specialties; meetings; monoamine; mortality; neurocognitive test; neuroimaging; neuropsychiatry; neurotransmission; older patient; open label; outreach; placebo controlled study; programs; psychostimulant; randomized placebo controlled trial; response; reuptake; symposium; trait; transmission process; treatment response; treatment strategy; treatment trial

DESCRIPTION (provided by applicant): Fewer than 50% of elderly depressed patients achieve remission and functional recovery in response to first-line antidepressant pharmacotherapy. The majority of patients are left with significant residual symptoms, putting them at risk of chronic, relapsing illness, frailty, and suicide. Improved understanding of neurobiology of geriatric depression and mechanisms of treatment response may lead to the improved clinical management of this pervasive and disabling disorder. While the serotonin system has been the focus of pharmacotherapy in unipolar major depression, there is a compelling rationale for the study of other monoamine systems. Impairment of executive functions persists even after amelioration of depressive symptoms and that these symptoms are poorly responsive to serotonergic treatment alone. We hypothesized that the addition of methylphenidate (MPH) to the serotonergic drug, citalopram, may result in better clinical outcomes of the affective and cognitive symptoms of late life depression. These considerations provided the impetus for our pilot study to evaluate the treatment response of the combination of citalopram and methylphenidate (MPH) compared to citalopram and placebo. We observed enhanced antidepressant response and improvement in executive cognitive function tests to a combination of citalopram and methylphenidate (MPH). The improvement in executive function was greater in patients who were homozygous for the dopamine transporter genotype (DAT VNTR10/10). The current proposal will evaluate the role of adjunctive MPH treatment to determine the effects of pharmacologic increase of dopamine on the clinical and cognitive response to selective serotonin reuptake (SSRI) treatment. We will also explore the role of the candidate genes involved in the regulation of dopaminergic neurotransmission (i.e., COMT, DAT1, DRD4) and sertonergic neurotransmission (i.e., HTR2A) in the clinical and cognitive response to treatment with methylphenidate and citalopram. We will recruit 168 elderly non-demented subjects with major depression to participate in a double-blind randomized placebo- controlled trial. Participants will be randomly assigned to three groups: one group will receive combination of citalopram and MPH, the second group will receive MPH and placebo, and the third group will receive citalopram and placebo. All subjects will undergo comprehensive medical, neuropsychiatric and cognitive assessments, and genetic testing at baseline and over the 16 weeks of treatment. Our study will provide the unique information regarding the use of methylphenidate to improve cognitive and clinical outcomes, and will shed light on the underlying mechanism of treatment response in geriatric depression. Evaluating selected dopamine-related genes in late-life depression with respect to mood and cognitive symptoms, and treatment response may lead to the development of the targeted individualized treatments in geriatric depression.

描述（由申请人提供）：不到50％的老年抑郁症患者可以响应一线抗抑郁药药物治疗，从而获得缓解和功能恢复。大多数患者都有明显的残留症状，使他们处于慢性，复发，脆弱和自杀的风险。对老年抑郁症的神经生物学的理解和治疗反应机制的理解可能会导致这种普遍存在和残疾疾病的临床管理。虽然5-羟色胺系统一直是单极重大抑郁症的药物疗法的重点，但研究其他单胺系统仍有令人信服的理由。即使在改善抑郁症状后，行政功能的损害仍然存在，并且仅对血清素能治疗的反应很差。我们假设在血清素能药物Citalopram中添加哌醋甲酯（MPH）可能会导致晚期抑郁症的情感和认知症状的更好的临床结局。这些考虑因素为我们的试点研究提供了动力，以评估与西妥位丙酰胺和安慰剂相比，西妥丙酰胺和哌醋甲酯（MPH）组合的治疗反应。我们观察到对抗抑郁功能测试的抗抑郁反应增强，并改善了对西妥丙酰胺和哌醋甲酯（MPH）的组合。在多巴胺转运蛋白基因型（DAT VNTR10/10）的纯合患者中，执行功能的改善更大。当前的建议将评估辅助MPH治疗的作用，以确定多巴胺对临床和认知反应对选择性5-羟色胺再摄取（SSRI）治疗的影响。我们还将探讨候选基因在调节多巴胺能神经传递（即COMT，DAT1，DRD4）和SERTONERGIC神经传递（即HTR2A）中的作用。我们将招募168名具有重度抑郁症的老年人非痴呆的受试者，参加一项双盲随机安慰剂控制试验。参与者将被随机分配给三个组：一组将接收Citalopram和MPH的组合，第二组将接收MPH和安慰剂，第三组将接受西妥位酰胺和安慰剂。所有受试者都将接受全面的医学，神经精神和认知评估，以及基线和治疗16周时的基因检测。我们的研究将提供有关使用哌醋甲酯来改善认知和临床结果的独特信息，并将阐明老年抑郁症治疗反应的潜在机制。在情绪和认知症状方面，评估晚期抑郁症中选定的多巴胺相关基因，治疗反应可能会导致老年抑郁症中靶向个性化治疗的发展。