Naturalistic Study of Ketamine in the Treatment of Depression

Hospital de Clinicas de Porto Alegre

Status: Active, not recruiting

Conditions: Major Depressive Disorder; Bipolar II Disorder; Bipolar I Disorder; Bipolar Disorder; Bipolar Depression; Affective Disorder

Treatments: Drug: Ketamine

Study type: Observational

Funder types: Other

Identifiers

NCT05249309

2020-0334

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

90 participants in 2 patient groups

Treatment

Description:

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.

Treatment:

Drug: Ketamine

Control

Description:

Will be checked weight, height and waist circumference and collected about 15 mL of peripheral blood.