Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- The Montgomery-Asberg Depression Rating Scale
研究概览
简要总结
The Investigators are conducting a research study to learn about the safety and benefit of using a medication called buprenorphine for patient with difficult to treat depression . This research study is testing whether combining two medications will be effective in treating depression when initial treatment with just one antidepressant does not relieve the depressive symptoms ; this is what is called " difficult to treat depression " or " treatment resistant depression ". The two medication the investigators are using are " an anti-depressant medication called venlafaxine XR ( the generic form of Effexor ) and buprenorphine . Buprenorphine is a medication that is FDA approved for the treatment of opioid dependence. The investigators are testing whether adding buprenorphine to venlafaxine enhances treatment response.
详细描述
The aim of this study is to examine the feasibility, safety, and tolerability of buprenorphine (BPN) as a novel treatment for late-life treatment resistant depression (LL-TRD). The investigators aim to use a clinical trial methodology common to all three sites, and to examine the mechanism of action (MOA) of BPN using translational neuroscience methods. Over ½ of seniors with depression fail to respond to traditional antidepressants.19,20 Modulation of the opiate system with BPN offers a novel mechanistic approach to improve the lives of patients with LL-TRD, with a safety profile potentially superior to current augmentation strategies such as antipsychotics, lithium, ECT, and surgical interventions (e.g., deep brain or vagal nerve stimulation).
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 50 years
- •Major depressive disorder (MDD), single or recurrent, as diagnosed by the SCID-IV (or SCID-5 if available)
- •MADRS > 15
- •Has or agrees to establish a clinical relationship with primary care physician (PCP).
- •Availability of an informant (e.g., emergency contact) is encouraged but not required for study participation
排除标准
- •Inability to provide informed consent
- •Depressive symptoms not severe enough (i.e., MADRS < 15) at the baseline assessments
- •Dementia, as defined by 3MS < 80 and clinical evidence of dementia
- •Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the SCID
- •Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and score of > 8 on AUDIT-C and confirmed by study physician interview
- •High risk for suicide (e.g., active SI and/or current/recent intent or plan) AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases
- •Contraindication to venlafaxine or buprenorphine as determined by PCP and study physician including history of intolerance of either venlafaxine or buprenorphine in the study target dosage range (venlafaxine at up to 300 mg/day; buprenorphine at up to 1.2 mg/day)
- •Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English)
- •Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)
- •Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. This will be determined based on information from the patient's personal physician and study physician's clinical judgment. Referral to the patient's personal physician or to a general practitioner will be made in these cases
- •Subjects taking psychotropic medications that cannot be safely tapered and discontinued prior to study initiation. The following exceptions are allowed if they have been taken at a stable dose for at least 4 weeks prior to study entry and there is not a plan to change the dose during the next 32 -36 weeks: benzodiazepines up to 2 mg/d lorazepam equivalent; other sedative-hypnotics (e.g., zolpidem, zaleplon, eszopiclone); gabapentin if prescribed for non-psychiatric indication (e.g., neuropathy)
- •History of opiate abuse or dependence
- •Severe pain, defined as > 7 on 0-10 numeric rating scale for pain
- •Concomitant use of strong or moderate CYP3A4 inhibitor (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketonazole, nefazodone, saquinovir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem)
- •Refusal to stop all opioids (to avoid precipitating opioid withdrawal)
- •Refusal to discontinue all alcohol (to reduce the risk of respiratory depression)
- •Hepatic impairment (AST/ALT > 1.5 times upper normal)
- •Estimated Glomerular Filtration Rate (GFR) < 20 ml/min
- •Inability/refusal to identify a person as an emergency contact
研究组 & 干预措施
venlafaxine XR plus buprenorphine
Drug Intervention: venlafaxine XR plus buprenorphine Dosage varies. Subject remains on antidepressant throughout the 32 week study. Will be randomized to buprenorphine or placebo for up to 16 weeks.
干预措施: venlafaxine (Drug)
venlafaxine XR plus buprenorphine
Drug Intervention: venlafaxine XR plus buprenorphine Dosage varies. Subject remains on antidepressant throughout the 32 week study. Will be randomized to buprenorphine or placebo for up to 16 weeks.
干预措施: buprenorphine (Drug)
venlafaxine XR plus placebo
Drug Intervention: venlafaxine XR plus placebo Dosage varies . Subject remains on antidepressant throughout the 32 weeks study. Will be randomized to buprenorphine or placebo for up to 16 weeks
干预措施: venlafaxine (Drug)
venlafaxine XR plus placebo
Drug Intervention: venlafaxine XR plus placebo Dosage varies . Subject remains on antidepressant throughout the 32 weeks study. Will be randomized to buprenorphine or placebo for up to 16 weeks
干预措施: placebo (Drug)
结局指标
主要结局
The Montgomery-Asberg Depression Rating Scale
时间窗: 32 weeks
MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.
次要结局
- Brief Symptom Inventory for Anxiety(32 weeks)
- Numeric Scale of Pain ( NRS-P)(16 weeks)
- Antidepressant Side Effect Checklist (ASEC)(16 weeks)
- Suicidal Ideation Scale ( SIS)(32 weeks)
- Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)(16 weeks)
研究者
Daniel Blumberger
Dr. Daniel. M. Blumberger
Centre for Addiction and Mental Health