Clinical trial NCT04234776: Intramuscular Ketamine Versus Aripiprazole and Escitalopram in the Treatment of Resistant Depression
Official title: Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Depressive Disorder
Keywords: Ketamine
Treatment Resistant Depression
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2020-01-21
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will receive IM ketamine or IM saline applications as randomized. Applications will occur three times a week. It will be 4 weeks of IM application (12 initial applications). Injections will occur into the subjects' glutes (0.75 mg / kg). The ketamine group will use 2 placebo tablets and the parallel group escitalopram 15 mg and aripiprazole 5 mg. Thereafter, participants will receive weekly ketamine doses over 6 months as maintenance treatment. Research members will be submitted to Structured Clinical Interview for the DSM for diagnostic categorization and will be evaluated from other scales. Vital signs will be checked continuously for a period of 2 hours with each infusion. Patients will be observed in a quiet, comfortable room and subjected to medical monitoring for 2 hours. They will leave the environment in the company of a competent adult.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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)

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);
2. Moderate to severe intensity of the disease;
3. 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,
4. Literate and able to understand the tasks requested;
5. With clinical comorbidities, however compensated;
6. Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.

Exclusion Criteria:

1. Imminent risk of suicide;
2. Patients with psychoactive substance dependence;
3. Intellectual deficit and psychotic symptoms;
4. Bipolar spectrum disorders and other primary psychiatric diagnoses;
5. Allergic to ketamine;
6. Glaucoma;
7. Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;
8. Treatment with irreversible MAOI in two weeks prior to visit 0;
9. Fluoxetine treatment within 4 weeks prior to visit 0;
10. Treatment with others antidepressants;
11. Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;

    a. Lorazepam and zolpidem may be used;
12. Patients who become pregnant will be excluded from the study and referred for obstetric care.

Primary outcomes:
measure: Change in depressive symptoms
timeFrame: 3 times a week in once month (Phase II)
measure: Change in depressive symptoms
timeFrame: Once a week in six months (Phase III)
measure: Change in depressive symptoms
timeFrame: Once a week in once month (Phase IV)
Secondary outcomes:
measure: Depression symptoms
timeFrame: Through study completion, an average of 1 year.
measure: Clinical impressions-S
timeFrame: Through study completion, an average of 1 year.
measure: Clinical impressions-I
timeFrame: Through study completion, an average of 1 year.
measure: Electrocardiographic monitoring
timeFrame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
measure: Blood Pressure (BP [mmHg]).
timeFrame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
measure: Heart rate (HR [bpm]).
timeFrame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
measure: Digital pulse oximetry (%).
timeFrame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
measure: Respiratory rate (RR [cycles/min])
timeFrame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
measure: Suicide risk 1
timeFrame: Through study completion, an average of 1 year.
measure: Suicide risk 2
timeFrame: Through study completion, an average of 1 year.
measure: General side effects
timeFrame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
measure: Hypo/maniac symptoms
timeFrame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
measure: Dissociative symptoms
timeFrame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
measure: Psychotic symptoms
timeFrame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
measure: Depression thoughts
timeFrame: Through study completion, an average of 1 year.
measure: Stimate intelligence quocient
timeFrame: Through study completion, an average of 1 year.
measure: Intelligence quocient
timeFrame: Through study completion, an average of 1 year.
measure: Attention
timeFrame: Through study completion, an average of 1 year.
measure: Memory
timeFrame: Through study completion, an average of 1 year.
measure: Executive functions 1
timeFrame: Through study completion, an average of 1 year.
measure: Executive functions 2
timeFrame: Through study completion, an average of 1 year.
measure: Verbal fluency 1
timeFrame: Through study completion, an average of 1 year.
measure: Verbal fluency 2
timeFrame: Through study completion, an average of 1 year.
measure: Functional recovery 1
timeFrame: Through study completion, an average of 1 year.
measure: Functional recovery 2
timeFrame: Through study completion, an average of 1 year.
measure: Body Mass Index (BMI)
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 1
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 2
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 3
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 4
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 5
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 6
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 7
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 8
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 9
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 10
timeFrame: Through study completion, an average of 1 year.
measure: Clinical and psychiatric features 11
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 1
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 2
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 3
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 4
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 5
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 6
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 7
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 8
timeFrame: Through study completion, an average of 1 year.
measure: Epidemiological features 9
timeFrame: Through study completion, an average of 1 year.
Other outcomes:
Locations:
city: Blumenau
country: Brazil
facility: Núcleo de Pesquisas em Saúde Mental
state: Santa Catarina
Study officials:
affiliation: Department and Institute of Psychiatry, University of Sao Paulo
name: Ricardo A Moreno, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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