Bipolar Disorder, Major Depressive Disorder, Treatment Resistant Depression
Conditions
Brief summary
The primary objective of this study is to determine the effectiveness of serial infusions of intravenous (IV) ketamine in adults with treatment resistant depression (TRD).
Detailed description
Thus, in the current study we want to naturalistically explore the antidepressant effects of serial slow IV infusions (40 minutes) of ketamine at a dose of 0.5 mg/kg, over a treatment period of 8 weeks in an academic psychiatric hospital. This is a minimal sedation treatment. The primary outcome measure of this study will be remission estimated based on the severity of depressive scores. After the 8 weeks of treatment, there will be a four week observational period. During the observational period, participants will receive treatment as usual and will be contacted over the phone for follow-up questions regarding their overall health status, mood and clinical state. They will also complete a neurocognitive task at the end of the 4 week observational period
Interventions
DRUGKetamine
Ketamine will be infused (slow IV infusions of ketamine (0.5 mg/kg) over 40 minutes) twice weekly over a period of 4 weeks and weekly for the following 4 weeks of the study treatment period (8 weeks total).
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* patients with major depressive disorder (MDD) or bipolar disorder (BD) * patients with documented treatment resistant disorder (TRD) (according to Diagnostic Statistical Manual (DSM-IV TR)), and who have failed (defined as patient does not reach remission within the 8 week trial of an antidepressant or combination at a therapeutic dose) of at least two trials of first line evidence-based treatments and/or electroconvulsive therapy (ECT)
Exclusion criteria
* Being younger than 18 of age or older than 65. * Diagnosed with intellectual disability, e.g. mental retardation (MR), neurodegenerative diseases, e.g. early-onset neurocognitive disturbances such as frontotemporal dementia (FTD) or behavioral disorders, e.g. adult onset Attention Deficit Hyperactivity Disorder (ADHD). * Diagnosed with bipolar disorder not otherwise specified (BD-NOS) or rapid cycling BD * Diagnosed with personality disorders (PD). * Previously or currently diagnosed with psychosis (schizoaffective disorder - SAD) or schizophrenia - SCZ). * Current major medical problems that affect brain anatomy, neurochemistry, or function, e.g., obstructive sleep apnea requiring Continuous Positive Airway Pressure (CPAP), liver insufficiency, kidney insufficiency, cardiovascular problems, systemic infections, cancer, auto-immune diseases, and any brain disorder (seizure disorder, stroke, dementia, degenerative neurologic diseases); history of any brain diseases, including seizures, stroke, meningitis, encephalitis, dementia, degenerative brain diseases, and head injury with loss of consciousness for any period of time. * Diagnosed specifically with a cardiovascular disorders such as Arrhythmias, Chronic Heart Failure, Myocardial Infarction (MI) or suffering from Chronic Obstructive Pulmonary Disease (COPD) or asthma. Suffering from uncontrolled hypertension or diastolic BP over 100. Cardiac clearance prior to enrolling in the study/medical records from physician will be required per patient's primary care physician (PCP). * Patients with increased risk of laryngospasm, active upper respiratory infections, respiratory depression, increased intracranial pressure, hyperthyroidism, or porphyria. * Current substance abuse or dependence. Only patients who achieved stable, full remission for at least 6 months will be included. * Pregnancy or Breast feeding. All female in reproductive age will undergo pregnancy tests. Female participants will be required to provide evidence of use of contraceptives during the course of the study. * Unable to understand the design and requirements of the study * Unable to sign the informed consent for any reason * An assigned responsible adult has provided assent to assist in patient's study participation. The responsible adult agrees to be present at each study appointment as well as provide transportation to study appointments for the patient.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Will be Measured Through Number of Adverse Events | Baseline through week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Treatment Will be Measured on of Clinical Global Impressions (CGI) | Baseline, week 8, week 12 | — |
| Severity of Depressive Symptoms as Assessed by the PHQ-9 | Baseline, week 8, week 12 | The Patient Health Questionnaire (PHQ)-9 is the 9-item depression module from the full Patient Health Questionnaire (PHQ) PHQ-9 total score ranges from 0 to 27 (each of the 9 items can be scored from 0 (not at all) to 3 (nearly every day)), and a higher score indicates greater depression. |
Countries
United States
Participant flow
Pre-assignment details
Four participants who were enrolled met exclusion criteria and therefore did not start the study.
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Ketamine: Ketamine will be infused (slow IV infusions of ketamine (0.5 mg/kg) over 40 minutes) twice weekly over a period of 4 weeks and weekly for the following 4 weeks of the study treatment period (8 weeks total). | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Ketamine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Safety Will be Measured Through Number of Adverse Events
Time frame: Baseline through week 12
Population: This data was only collected for the 2 participants who completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Safety Will be Measured Through Number of Adverse Events | 2 adverse events |
Secondary
Efficacy of Treatment Will be Measured on of Clinical Global Impressions (CGI)
Time frame: Baseline, week 8, week 12
Population: Clinical Global Impressions (CGI) scale data was not collected for any participant
Secondary
Severity of Depressive Symptoms as Assessed by the PHQ-9
The Patient Health Questionnaire (PHQ)-9 is the 9-item depression module from the full Patient Health Questionnaire (PHQ) PHQ-9 total score ranges from 0 to 27 (each of the 9 items can be scored from 0 (not at all) to 3 (nearly every day)), and a higher score indicates greater depression.
Time frame: Baseline, week 8, week 12
Population: PHQ-9 data was collected at baseline for all 6 participants who started the study. PHQ-9 data was not collected at week 8 or week 12 for 4 participants, per study protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Severity of Depressive Symptoms as Assessed by the PHQ-9 | Baseline | 12.67 units on a scale | Standard Deviation 9.501 |
| Ketamine | Severity of Depressive Symptoms as Assessed by the PHQ-9 | Week 8 | 5 units on a scale | Standard Deviation 5.657 |
| Ketamine | Severity of Depressive Symptoms as Assessed by the PHQ-9 | Week 12 | 5 units on a scale | Standard Deviation 5.657 |