Mood Disorders
Conditions
Interventions
A pilot study will be conducted over a period of 58 weeks with patient follow-up, divided into two distinct phases. The first phase will consist of a prospective, randomized, controlled, double-blind,
for treatment-resistant bipolar disorder (TRBD), adjuvant subcutaneous ketamine plus 0.9% saline intramuscularly, and adjuvant intramuscular ketamine (0.5 mg/kg) plus 0.9% saline subcutaneously
for those at risk of suicidal intent, oral lithium carbonate at therapeutic doses with adjuvant subcutaneous ketamine and oral lithium carbonate at therapeutic doses with adjuvant intramuscular ketami
Sponsors
Hospital Universitário Walter Cantídio Universidade Federal do Ceará
Hospital Universitário Walter Cantídio Universidade Federal do Ceará
Eligibility
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Participants of either sex; aged between eighteen and sixty-five years; body weight of fifty kilograms to one hundred twenty kilograms; informed consent obtained prior to participation; effective contraceptive methods for sexually active heterosexual women of childbearing potential (blood or urine test requested during screening, on medication administration days, and in case of clinical doubt about pregnancy status during the observation period); clinical stability demonstrated by physical examination, medical history, vital signs, and twelve-lead electrocardiogram during screening; abnormalities allowed if deemed clinically insignificant by the principal investigator and documented in source records; agreement to receive standard pharmacological treatment for treatment-resistant depression, treatment-resistant bipolar depression, and/or suicidal risk, as assessed by the responsible physicians; treatment-resistant depression: current major depressive episode without psychotic features, confirmed by the Structured Clinical Interview for DSM-5 Disorders Clinical Trials Version, Montgomery-Åsberg Depression Rating Scale score of eighteen or higher, resistance to two or more antidepressants and/or adjunctive agents; treatment-resistant bipolar depression: current major depressive episode without psychotic features, confirmed by the Structured Clinical Interview for DSM-5 Disorders Clinical Trials Version, diagnosis of bipolar disorder type I or II according to DSM-5 criteria, absence of sustained symptomatic remission for at least eight weeks or intolerance to two different treatments; suicidal risk with Montgomery-Åsberg Depression Rating Scale score of twenty-eight or higher, current suicidal ideation with intention confirmed by the Columbia-Suicide Severity Rating Scale and Montgomery-Åsberg Depression Rating Scale item 10 score = 4
Exclusion criteria
Exclusion criteria: Manic episode limited to groups with treatment-resistant depression or suicidal intent; major depressive episode with psychotic features; schizophrenia or schizoaffective disorder as determined by the Structured Clinical Interview for DSM-5 Disorders Clinical Trials Version; alcohol or substance use disorder, excluding tobacco, or withdrawal symptoms requiring detoxification; inpatient or outpatient detoxification treatment within six months prior to screening; suicidal ideation or behavior primarily due to a condition other than major depressive disorder; current clinical diagnosis of autism spectrum disorder, neurocognitive disorders, or intellectual disability; history of seizures, except for childhood febrile seizures; malnutrition; inability to provide informed consent or comply with study requirements; pregnancy, lactation, or intention to become pregnant within the next twelve weeks; active infection with hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or COVID-19; history of traumatic brain injury within the last six months; history of hypersensitivity to the study medications or their excipients; use of monoamine oxidase inhibitors within fourteen days before screening; cardiac disease or abnormal cardiac repolarization, including a history of myocardial infarction, angina pectoris, or coronary artery revascularization within six months prior to the start of the study treatment; history of clinically significant cardiac arrhythmias, complete left bundle branch block, advanced atrioventricular block, including bifascicular block, Mobitz type two, or third-degree atrioventricular block within six months prior to the start of the study treatment; Fridericia-corrected QT interval (electrocardiographic trace measured from the beginning of the QRS complex to the end of the T wave) at rest of greater than or equal to four hundred fifty milliseconds for men or greater than or equal to four hundred sixty milliseconds for women at screening or prior to the first dose on day one; inability to determine the Fridericia-corrected QT interval (electrocardiographic trace measured from the beginning of the QRS complex to the end of the T wave); risk factors for Torsades de Pointes, including uncorrected hypokalemia or hypomagnesemia, history of heart failure, or history of clinically significant or symptomatic bradycardia, long QT syndrome, family history of sudden unexplained death or congenital long QT syndrome; concomitant medication with a known risk of Torsades de Pointes that cannot be discontinued or replaced with a safe alternative medication seven days before screening and throughout the double-blind phase; average systolic blood pressure greater than one hundred forty millimeters of mercury or diastolic blood pressure greater than ninety millimeters of mercury at screening and before the first dose of medication on day one; elevated blood pressure or intracranial pressure that poses a serious risk, including vascular disease such as aneurysm and a history of intracerebral hemorrhage; any other condition, including liver disease or malignancy, that, according to the principal investigator's assessment, compromises the participant's safety; evidence of significant renal impairment indicated by an estimated glomerular filtration rate of less than forty milliliters per minute per one point seventy-three square meters at screening; use of other investigational medications within thirty days before screening; women of ch
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The groups submitted to the usual pharmacological treatment associated with intramuscular or subcutaneous ketamine will show a response and remission of the depressive episode in six weeks, as measured by the Montgomery Åsberg Depression Rating Scale (MADRS) score in patients with treatment-resistant unipolar depression, treatment-resistant bipolar depression, or risk of suicide with intent | — |
Secondary
| Measure | Time frame |
|---|---|
| The intramuscular (SC) route of administration of ketamine will result in fewer adverse events of special interest, such as dissociation and vital parameters, compared to the intramuscular (IM) route;Salivary cortisol measurement at different times throughout treatment could be a predictor of response to ketamine use in patients with treatment-resistant unipolar depression, treatment-resistant bipolar depression, or risk of suicide with intent;The groups treated with lithium carbonate associated with intramuscular or subcutaneous ketamine will show a response in reducing the risk of suicide measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) item 10 - suicidal ideation, in patients at risk of suicide and with intent;The impact of ketamine on the composition of the intestinal microbiota could be a predictor of response to the use of ketamine in patients with treatment-resistant unipolar depression, treatment-resistant bipolar depression, or risk of suicide with intent;The measurement of serum and salivary biomarkers could help to understand the pathophysiological mechanisms of patients with ;The composition of the intestinal microbiota may help to understand the pathophysiological mechanisms in patients with treatment-resistant unipolar depression, treatment-resistant bipolar depression, or risk of suicide with intent;To investigate the relationship between childhood maltreatment, as a possible poor predictor of response to treatment, assessed using the Childhood Trauma Questionnaire (CTQ), and response to treatment, using the Montgomery-Åsberg Depression Rating Scale (MADRS), in patients with treatment-resistant unipolar depression, treatment-resistant bipolar depression, or risk of suicide with intent;To investigate the relationship between affective and emotional temperaments, assessed using the Affective and Emotional Composite Temperament Scale (AFECTS), and response to treatment, using the Montgomery-Åsberg Depression Rating Scale (MADRS), in pati | — |
Countries
Brazil
Contacts
Public ContactFabio Souza
Hospital Universitário Walter Cantídio da Universidade Federal do Ceará - HUWC/UFC
Outcome results
None listed