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.
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)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
88
(0,75 mg/kg) saline solution (15 mg) Escitalopram (5 mg) Aripiprazole
Composite tools
MADRS (10) and HAM-D (3)
EPD
Quality of life and disability
Variables and categories
Vital signs
UKU-SERS, YOUNG, CADSS and BPRS-12.
Núcleo de Pesquisas em Saúde Mental
Blumenau, Santa Catarina, Brazil
Change in depressive symptoms
Montomery-Åsberg Depression Rating Scale (\[0-60\] higher scores: worse outcome). No improvement: MADRS ≤ 25% Partial response: MADRS ≥ 25% and \< 50% Response: MADRS ≥ 50% Remission: MADRS ≤10
Time frame: 3 times a week in once month (Phase II)
Change in depressive symptoms
Montgomery-Åsberg Depression Rating Scale (\[0-60\] higher scores: worse outcome). Recovery: Maintenance ≥ 6-8 months Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria)
Time frame: Once a week in six months (Phase III)
Change in depressive symptoms
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).
Time frame: Once a week in once month (Phase IV)
Depression symptoms
Hamiltom Depression Ratins Scale (HAM-D \[0-50\] higher scores: worse outcome).
Time frame: Through study completion, an average of 1 year.
Clinical impressions-S
Clinical Global Impression Scale (CGI \[0-7\] higher scores: worse outcome).
Time frame: Through study completion, an average of 1 year.
Clinical impressions-I
Clinical Global Impression Scale (CGI \[0-7\] higher scores: worse outcome).
Time frame: Through study completion, an average of 1 year.
Electrocardiographic monitoring
P wave, PR interval, QRS complex, J-point, ST segment, T wave, Corrected QT interval and U wave Rhythm (irregular rhythm: worse outcome).
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Blood Pressure (BP [mmHg]).
BP low \<90/60 (systolic/diastolic) mmHg and high \>140/90 mmHg ( (systolic/diastolic).
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Heart rate (HR [bpm]).
Anormal HR \<60 bpm or \>100 bpm.
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Digital pulse oximetry (%).
Low oxygen saturation \<95%.
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Respiratory rate (RR [cycles/min])
Anormal RR \<10 cycles/min or \>20 cycles/min.
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Suicide risk 1
Montgomery-Åsberg Depression Rating Scale (item 10 \[0-6\] higher scores: worse outcome).
Time frame: Through study completion, an average of 1 year.
Suicide risk 2
Hamilton Depression Rating Scale (item 3 \[0-4\] higher scores: worse outcome).
Time frame: Through study completion, an average of 1 year.
General side effects
Ugvalg for Kliniske Undersgelser-Side Effect Rating Scale (UKU-SERS \[48 specific symptoms).
Time frame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Hypo/maniac symptoms
Young Mania Rating Scale (YOUNG \[0-58\] higher scores: worse outcome).
Time frame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Dissociative symptoms
Clinician-Administered Dissociative State Scale (CADSS \[0-108\] higher scores: worse outcome)
Time frame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Psychotic symptoms
Brief Psychiatric Rating Scale (item 12 \[0-6\] higher scores: worse outcome).
Time frame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Depression thoughts
Depression Thoughts Scale (EPD \[1-78\] higher scores: worse outcome)
Time frame: Through study completion, an average of 1 year.
Stimate intelligence quocient
Wechsler Abreviated Scale of Intelligence (WASI \[70-160 percentille\] higher scores: better outcomes).
Time frame: Through study completion, an average of 1 year.
Intelligence quocient
Wechsler Scale of Intelligence (WAIS III \[70-155 percentille\] higher scores: better outcomes).
Time frame: Through study completion, an average of 1 year.
Attention
Trial Making Test (5-95 percentille, higher scores: better outcomes).
Time frame: Through study completion, an average of 1 year.
Memory
Rey figures (10-100 percentille, higher scores: better outcomes)
Time frame: Through study completion, an average of 1 year.
Executive functions 1
Wisconsin Test (50-\>80 score, higher scores: better outcomes).
Time frame: Through study completion, an average of 1 year.
Executive functions 2
Stroop Color Word Test (5-95 percentille, higher scores: better outcomes)
Time frame: Through study completion, an average of 1 year.
Verbal fluency 1
Verbal Fluency Test (FAS \[10-90 percentille\], higher scores: better outcomes))
Time frame: Through study completion, an average of 1 year.
Verbal fluency 2
The Rey Auditory-Verbal Learning Test (RAVLT \[5-95 percentille\], higher scores: better outcomes).
Time frame: Through study completion, an average of 1 year.
Functional recovery 1
World Health Organization Quality of Life (WHOQOL-brief \[4 domains, 26 questions higher scores: better outcome\]).
Time frame: Through study completion, an average of 1 year.
Functional recovery 2
Sheehan Disability Scale (SDS \[0-30\] higher scores: worse outcome).
Time frame: Through study completion, an average of 1 year.
Body Mass Index (BMI)
Weight and height (kg/m2).
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 1
Disease intensity (HAM-D \[% of patients\], moderate or severe)
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 2
Number of episodes (questionnaire \[incidence\])
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 3
Current episode duration (questionnaire \[years\])
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 4
Suicide attempts (questionnaire \[% of pacients\])
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 5
History of physical abuse (questionnaire \[% of pacients\])
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 6
History of sexual abuse (questionnaire \[% of pacients\])
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 7
Psychiatric hospitalizations (questionnaire \[% of pacients\])
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 8
Clinical comorbidities (questionnaire \[% of patients\]).
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 9
Family history of depression (questionnaire \[% of patients\])
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 10
Family history of bipolar disorders (questionnaire \[% of patients)
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 11
Family history of other mental disorders (questionnaire \[% of patients\]).
Time frame: Through study completion, an average of 1 year.
Epidemiological features 1
Age (questionnaire \[years\]).
Time frame: Through study completion, an average of 1 year.
Epidemiological features 2
Gender (questionnaire \[% of patients\]; male/female)
Time frame: Through study completion, an average of 1 year.
Epidemiological features 3
Marital status (questionnaire \[% of patients\] single, married, separated, divorced or widower).
Time frame: Through study completion, an average of 1 year.
Epidemiological features 4
Ethnicity (questionnaire \[% of patients\])
Time frame: Through study completion, an average of 1 year.
Epidemiological features 5
Religion (questionnaire \[% of patients\] protestant, pentecostal or neopentecostal, spiritism, afro-brazilian, no religion or atheism and others\]).
Time frame: Through study completion, an average of 1 year.
Epidemiological features 6
Occupation (questionnaire \[% of patients\])
Time frame: Through study completion, an average of 1 year.
Epidemiological features 7
Education (questionnaire \[years\])
Time frame: Through study completion, an average of 1 year.
Epidemiological features 8
Individual income (questionnaire \[dollars\]).
Time frame: Through study completion, an average of 1 year.
Epidemiological features 9
Family income (questionnaire \[dollars\]).
Time frame: Through study completion, an average of 1 year.
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