Naturalistic Study of Ketamine in the Treatment of Depression

Hospital de Clinicas de Porto Alegre90 enrolled

Overview

This study aims to examine the effect of ketamine in decreasing the risk of suicide in patients with depression and its effectiveness as an antidepressant agent.

Mood disorders are chronic, recurrent, and highly prevalent health conditions worldwide. Major depression and bipolar disorder are often associated with psychosocial functional impairments and general medical conditions. Furthermore, suicide figures as one of the most important negative outcomes of mood disorders. In this sense, according to the World Health Organization (WHO), psychiatric disorders are associated with more than 90% of cases of complete suicide and are responsible for 30% of reported suicide cases worldwide. Suicide is a matter of concern for clinicians, not only because of the individual and familiar impact but also due to its social and population impact; then, research involving new potential treatments for suicide behavior ate highly needed. The literature has shown that ketamine, a substance commonly used as an anesthetic, is effective in treating depressive symptoms. Considering the high rate of suicide among patients with mood disorders and its consequences, the aim of this naturalistic study is to investigate the effect of ketamine in reducing the risk of suicide in patients with a depressive episode. The hypothesis is that treatment with ketamine will result in an improvement in depressive symptoms as well as in a decrease in the risk of suicide. Therefore, forty-five patients will be recruited, with major depressive disorder, bipolar I disorder or bipolar II disorder and who were already on ketamine treatment prescribed by assistant psychiatrist (inclusion criteria). Patients will go on the standard protocol of ketamine 0.5mg/kg subcutaneously (SC) twice a week for one month in general. In line with a naturalistic approach, all changes in the protocol, in time and doses will be accepted, according to the assistant doctor prescription without study intervention. After this period, they could receive the same dose of the medication once a week for the third month. In addition, patients will be monitored by phone until month six. Forty-five participants without any personal or first-degree family history of psychiatry or neurologic disorders will be recruited to participate as controls. Biochemical analyses will be used to investigate inflammatory markers, transcription factors and other peripheral biomarkers in patients with mood disorders and healthy controls.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Major Depressive Disorder Bipolar Disorder Bipolar Depression Bipolar I Disorder Bipolar II Disorder Affective Disorder

Interventions

KetamineDRUG

The administration will be done subcutaneously, in the abdominal wall, using ketamine without dilution. The ketamine dose will be 0.5mg/kg, recommended for the first infusion. If there is no adequate response, according to psychiatric scales and clinical evaluation, the second infusion must be performed at least two days after the first, using 0.75mg/kg and the subsequent 1mg/kg. If the patient adequately responds to a dose (0.5 or 0.75mg/kg), it should be repeated after over twice weekly over a period of 4 weeks.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria Having a diagnosis according to DSM-5 for * Major depressive episode as part of either Major depressive disorder, Bipolar I disorder, or Bipolar II disorder according to Fifth Edition of Diagnostic and Statistical Manual for Mental Disorders (DSM-5); * 18 years old or older; * Be able to provide written informed consent.episode; * MADRS scale total score ≥ 12 and score in items 1 (apparent sadness) and 2 (expressed sadness) ≥ 2 during the screening period (baseline); * YMRS scale total score ≤ 11 at baseline; * Having current symptoms of suicidal ideation and/or behavior, according to the C-SSRS scores; * Use of effective contraceptive methods in the case of heterosexual women of childbearing age; * Indication/prescription of the attending physician for the use of ketamine, subcutaneous; * For the patients with Bipolar I disorder: currently using lithium, valproic acid, or atypical antipsychotic at therapeutic doses for at least four weeks prior to initial evaluation. * For patients with Bipolar II disorder: currently using lithium, valproic acid, lamotrigine, or atypical antipsychotic at therapeutic doses for at least four weeks prior to initial evaluation. Exclusion Criteria * Patients with an unstable, defined, or suspected systemic medical condition; * Women who are pregnant, breastfeeding or planning to become pregnant within the next year; * Patients who cannot tolerate the use of ketamine or who have previous adverse effects associated with ketamine; * Inability to comply with informed consent or treatment protocol needs; * Patients currently with psychotic symptoms (according to DSM-5 criteria); * Patients with a current diagnosis of any active substance use disorder according to the MINI/DSM-5 criteria (with the exception of tobacco); * Patients with autoimmune or inflammatory conditions, cancer or active infectious diseases.

Locations (2)

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Outcomes

Primary Outcomes

Changes in Columbia Suicide Severity Rating Scale (C-SSRS) - Ideation Severity

Intensity of ideation was measured using the C-SSRS for Suicide Ideation intensity of ideation item. Item responses range from 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent), with higher scores indicating more severe ideation.

Time frame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24

Changes in Columbia Suicide Severity Rating Scale (C-SSRS) - Behavior

Items measuring attempt behavior (number of Actual Attempts, number of Aborted Attempts, number of Interrupted Attempts) From the C-SSRS were summed to create a composite variable indexing attempt behavior. Higher scores indicate more attempt behavior.

Time frame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24

Secondary Outcomes

Change in depressive symptoms according to Hamilton Depression Rating Scale (HAMD)

Change from baseline in HAMD score. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).

Time frame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24

Change in psychotic symptoms according to Brief Psychiatric Rating Scale (BPRS)

Change from baseline in BPRS score. Scale range: from 0 to 108. Higher values represent more severe symptoms of psychosis.

Time frame: For Weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24

Change in depressive symptoms according to Montgomery-Asberg Depression Rating Scale (MADRS)

MADRS is a 10-item rating scale for depressive mood symptoms severity, items rated on 0-6 scale, with total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

Data from ClinicalTrials.gov

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