Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression
试验速览
- 阶段
- 4 期
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Change in depressive symptoms
研究概览
简要总结
The treatment of resistant depression should be optimized aiming at complete remission of symptoms, a complex condition due to several factors. Approximately 1/3 of patients with depressive disorders do not even respond to available antidepressants. Consequently, new molecules with robust action, fast effects and sustained improvement are currently being researched worldwide. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a promising alternative due to its involvement in neurogenesis, synaptogenesis and consequent rapid improvement of depressive and suicidal symptoms with traditional intravenous (IV) use in sub dose (0.5 mg / kg). The therapeutic response of IV use has been short and requires monitoring in a hospital setting. There are no studies evaluating response to long-term ketamine use. Recent research has focused on identifying other routes of ketamine use such as intranasal and intramuscular (IM). The use of ketamine IM, despite the fact that there are few studies and small samples, can demonstrate efficacy in acute treatment and maintenance of depression, as well as low profile of side effects, greater accessibility potential, reduced costs and risks, patient comfort and possible expansion of resistant depression treatment capabilities in different settings.
详细描述
Compare the response of ketamine IM versus active control in treatment-resistant depression (TRD [primary outcome]) and find safety and tolerability of ketamine IM, evaluate changes in life quality, cognition and suicidal risk (secondary outcomes)
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
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);
- •Moderate to severe intensity of the disease;
- •Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);
- •a. Blood test will be requested at the diagnostic stage and in case of clinical doubt as to the patient's gestational status,
- •Literate and able to understand the tasks requested;
- •With clinical comorbidities, however compensated;
- •Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.
排除标准
- •Imminent risk of suicide;
- •Patients with psychoactive substance dependence;
- •Intellectual deficit and psychotic symptoms;
- •Bipolar spectrum disorders and other primary psychiatric diagnoses;
- •Allergic to ketamine;
- •Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;
- •Treatment with irreversible MAOI in two weeks prior to visit 0;
- •Fluoxetine treatment within 4 weeks prior to visit 0;
- •Treatment with others antidepressants;
- •Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;
- •a. Lorazepam and zolpidem may be used;
- •Patients who become pregnant will be excluded from the study and referred for obstetric care.
研究组 & 干预措施
Rapid-acting antidepressant
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
干预措施: Cognition (Diagnostic Test)
Rapid-acting antidepressant
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
干预措施: Ketamine (Drug)
Rapid-acting antidepressant
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
干预措施: Suicide risk (Other)
Rapid-acting antidepressant
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
干预措施: Depression thoughts (Other)
Rapid-acting antidepressant
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
干预措施: Quality of life and disability (Other)
Rapid-acting antidepressant
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
干预措施: Clinical and epidemiological factors (Other)
Rapid-acting antidepressant
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
干预措施: Safety of ketamine IM (Device)
Rapid-acting antidepressant
Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
干预措施: Tolerability of ketamine IM (Other)
Comparator
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
干预措施: Ketamine (Drug)
Comparator
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
干预措施: Cognition (Diagnostic Test)
Comparator
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
干预措施: Suicide risk (Other)
Comparator
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
干预措施: Depression thoughts (Other)
Comparator
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
干预措施: Quality of life and disability (Other)
Comparator
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
干预措施: Clinical and epidemiological factors (Other)
Comparator
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
干预措施: Safety of ketamine IM (Device)
Comparator
Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized
干预措施: Tolerability of ketamine IM (Other)
结局指标
主要结局
Change in depressive symptoms
时间窗: Once a week in once month (Phase IV)
Montgomery-Åsberg Depression Rating Scale (\[0-60\] higher scores: worse outcome). Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria).
次要结局
- Body Mass Index (BMI)(Through study completion, an average of 1 year.)
- Clinical impressions-S(Through study completion, an average of 1 year.)
- Digital pulse oximetry (%).(3 times a week in once month (Fase II) and once a week in six months (Phase III))
- Clinical impressions-I(Through study completion, an average of 1 year.)
- Blood Pressure (BP [mmHg]).(3 times a week in once month (Fase II) and once a week in six months (Phase III))
- Respiratory rate (RR [cycles/min])(3 times a week in once month (Fase II) and once a week in six months (Phase III))
- Depression symptoms(Through study completion, an average of 1 year.)
- Electrocardiographic monitoring(3 times a week in once month (Fase II) and once a week in six months (Phase III))
- Suicide risk 2(Through study completion, an average of 1 year.)
- General side effects(3 times a week in once month (Phase II) and once a week in six months (Phase III))
- Hypo/maniac symptoms(3 times a week in once month (Phase II) and once a week in six months (Phase III))
- Dissociative symptoms(3 times a week in once month (Phase II) and once a week in six months (Phase III))
- Psychotic symptoms(3 times a week in once month (Phase II) and once a week in six months (Phase III))
- Depression thoughts(Through study completion, an average of 1 year.)
- Stimate intelligence quocient(Through study completion, an average of 1 year.)
- Intelligence quocient(Through study completion, an average of 1 year.)
- Attention(Through study completion, an average of 1 year.)
- Heart rate (HR [bpm]).(3 times a week in once month (Fase II) and once a week in six months (Phase III))
- Suicide risk 1(Through study completion, an average of 1 year.)
- Memory(Through study completion, an average of 1 year.)
- Executive functions 1(Through study completion, an average of 1 year.)
- Executive functions 2(Through study completion, an average of 1 year.)
- Verbal fluency 1(Through study completion, an average of 1 year.)
- Verbal fluency 2(Through study completion, an average of 1 year.)
- Functional recovery 1(Through study completion, an average of 1 year.)
- Functional recovery 2(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 1(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 2(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 3(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 5(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 6(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 8(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 9(Through study completion, an average of 1 year.)
- Epidemiological features 8(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 4(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 11(Through study completion, an average of 1 year.)
- Epidemiological features 5(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 7(Through study completion, an average of 1 year.)
- Clinical and psychiatric features 10(Through study completion, an average of 1 year.)
- Epidemiological features 1(Through study completion, an average of 1 year.)
- Epidemiological features 2(Through study completion, an average of 1 year.)
- Epidemiological features 3(Through study completion, an average of 1 year.)
- Epidemiological features 4(Through study completion, an average of 1 year.)
- Epidemiological features 6(Through study completion, an average of 1 year.)
- Epidemiological features 9(Through study completion, an average of 1 year.)
- Epidemiological features 7(Through study completion, an average of 1 year.)
研究者
Ricardo Alberto Moreno, M.D., Ph.D.
Study principal investigator
University of Sao Paulo