Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Proportion of Participants Retained in Study Through 2-Month Follow-Up
研究概览
简要总结
The goal of this clinical trial is to understand the effect of ketamine on the brain in people with treatment-resistant depression (TRD). TRD occurs in around a third of people with depression and leads to higher suicide rates compared to those with major depressive disorder. A desperate need for a rapid acting antidepressant drug (RAAD) is needed to help improve quality of life for people with TRD. Ketamine has been shown to be a RAAD, and esketamine (a form of ketamine) was approved by the FDA to treat TRD. Ketamine has been known to cause dissociative experiences, that can lead to an increase in the "Openness to Experience" personality trait and psychological flexibility that occurs at "peak experience". This has been shown to improve mental health conditions and lower suicide risk. This study aims to further understand if there is a connection between this new change of mind and changes in brain activity. Ketamine has been shown to improve brain plasticity as well, specifically in the frontolimbic region of the brain, an area associated with depression. The investigators are analyzing the brain using functional magnetic resonance imaging (fMRI), a method used to measure brain activity. The frontolimbic region is also associated with cognitive flexibility and emotional processing, an important hurdle in treating TRD. Due to this, the investigators are pairing the ketamine treatment with psychotherapy sessions, to guide the processing experience, which can lead to higher emotional flexibility.
The main questions this study aims to answer are:
- Are frontolimibic plasticity circuitry changes associated with openness to experience and peak experience?
- Is it feasible to recruit and retain people through a two-month KAP study?
- Is the structure of the study effective for treating TRD?
Participants will:
- Visit the facilities 6-8 times
- Complete 2 MRI brain scans
- Complete 3-4 psychotherapy sessions
- Receive 1-2 doses of ketamine
- Complete online surveys between 3-4 visits
详细描述
The proposed study is a single center study investigating the effect of ketamine modulation on the brain signature of treatment resistant depression (TRD). The patients will undergo 2 scanning visits (baseline and follow-up). They will also receive 1-2 treatments of ketamine IM injection and 3-4 psychotherapy sessions.
Patients with TRD will be asked to come to the PI's lab for 2 visits, and 6 in the Department of Psychiatry. On visit 1, after consenting and doing the drug screen, the subjects will be asked questions on their depression experience. Subjects will then fill out demographic and clinical questionnaire to assess mood, anxiety, pain, history of early trauma, and stress. Patients will be asked to rate their depression and pain level using a visual analogue scale (VAS).
During visit 1, Drs. Geha and Swogger will interview the patients to inquire about any prior drug allergies including allergies to medications that could be possibly used in this study (ketamine/ondansetron/lorazepam/clonidine). Possible side effects will be explained to the patients. They will then undergo 60 minutes of functional and structural brain scanning, which will serve as a baseline scan.
Visits 2 and 3 will be psychotherapy sessions with Dr. Swogger to prepare for the ketamine session and focus on their difficulties and goals for the medicine session. Strategies for working with ketamine will be reviewed.
Visits 4 and 6 will be the ketamine IM injection sessions. Visit 4 they will receive 0.5 mg/kg but will not exceed 60 mg regardless of weight. Visit 6 may be a higher dose, but will not exceed 60 mg. The dose will be determined by Drs. Geha and Swogger based on the patients' experience and response in visit 4. Ondansetron will be available for nausea, lorazepam for uncontrolled agitation, and clonidine for uncontrolled hypertension. Throughout the visits members of the study team will be present to ensure patient comfort and offer reassurance, redirection, etc. They will also take notes for later processing in psychotherapy visits. When the patient emerges from non-ordinary state of consciousness, they will complete the MEQ, and the study team will complete CADSS-6 and record any other pertinent information about the experience. Once it is deemed safe, the patient may leave via someone driving them home after the visit and will be instructed on safety measures for the rest of the day.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The following inclusion criteria must be met for all subjects to be considered eligible to participate:
- •18 years old or older
- •Able to speak, read, and understand English
- •In generally stable health
- •Must have treatment resistant depression, as defined as scoring in the moderate or above range on the HDRS and having failed two adequate trials of antidepressants in the last two years.
排除标准
- •General exclusion criteria for all subjects include:
- •Uncontrolled hypertension
- •Impaired cardiac status
- •a. Abnormal ECG report in the last month prior to screening
- •Chronic Obstructive Pulmonary Disease
- •Congenital Long QT Syndrome
- •≥265lbs or 120kg
- •Severe obesity (BMI ≥40)
- •Increased intracranial or cerebrospinal pressure
- •Pregnancy or breastfeeding
- •Hyperthyroidism
- •Prior adverse response to ketamine, including allergic reaction
- •Symptoms of psychosis or prodromal phase
- •Severe personality disorder
- •Autistic Spectrum Disorders
- •Bipolar disorder
- •History of substance abuse, defined as a score of three or more on Drug Abuse scale (prior use of psychedelics allowed)
- •Past-year suicide attempt or ongoing ideation with intent to act
- •All exclusion criteria for magnetic resonance imaging safety: any metallic implants, brain or skull abnormalities, tattoos on large body parts, and claustrophobia.
- •Taking medications that could interact with ketamine. Examples include but are not limited to: any types of stimulants, aripiprazole, diphenhydramine, hydromorphone, escitalopram, fluoxetine, alprazolam, and sertraline. Each subject's current medications will be evaluated for interactions with ketamine before admission into the trial.
研究组 & 干预措施
TRD group
干预措施: Ketamine hydrochloride injection (Drug)
结局指标
主要结局
Proportion of Participants Retained in Study Through 2-Month Follow-Up
时间窗: 2 months post-enrollment
Retention will be assessed as completion of all scheduled study assessments through the 2-month follow-up. A single value is derived for each participant, coded as 1 (retained) or 0 (not retained). Higher values indicate successful retention; lower values indicate dropout.
Mean Change in Hamilton Depression Rating Scale (HDRS) Total Score
时间窗: Baseline, once a day for up to 7 days after baseline, within 90 minutes after ketamine dosing session, once a day for up to 7 days after ketamine dosing session, once a day up to 7 days before 2-month follow-up, and at 2-month follow-up
Depression severity will be measured using the 17-item HDRS (items scored 0-2 or 0-4; total score range 0-52). A single value is derived by summing item scores. Higher scores indicate greater depression severity (worsening); lower scores indicate reduced severity (improvement). Mean change is calculated as post-treatment score minus baseline score.
次要结局
- Mean Change in NEO Five-Factor Inventory-3 (NEO-FFI-3) Openness Subscale Score(Baseline and 2-month follow-up.)
- Mean Acceptability Rating of Ketamine-Assisted Psychotherapy(At 2 month follow-up)
- Proportion of Participants Reporting Adverse Events (AEs)(Throughout the 8-week study.)
- Mean Change in Numerical Pain Rating Scale Score(Baseline, once a day for up to 7 days after baseline, within 90 minutes after ketamine dosing session, once a day for up to 7 days after ketamine dosing session, once a day up to 7 days before 2-month follow-up, and at 2-month follow-up)
研究者
Paul Geha
Associate Professor - Department of Psychiatry, Research (SMD)
University of Rochester