Treatment Resistant Depression, Electroconvulsive Therapy, ECT, Ketamine, Psychiatric Disorder, Depression, Major Depressive Disorder, Major Depressive Episode, Unipolar Depression
Conditions
Brief summary
The goal of the study is to conduct a comparative randomized trial of electroconvulsive therapy (ECT) vs. ketamine for patients with treatment resistant depression (TRD) in a real world setting with patient reported outcomes as primary and secondary outcome measures.
Detailed description
Patients with treatment resistant depression who meet all inclusion criteria and do not meet any exclusion criteria will be randomized to either electroconvulsive therapy (ECT) three times per week or ketamine infusion two times per week. Patients will answer questionnaires about their symptoms prior to treatments. The acute treatment phase of the study will last three to five weeks. Depending on response to treatment, some patients will be followed for an additional six months.
Interventions
PROCEDUREelectroconvulsive therapy (ECT)
ECT is a procedure done under general anesthesia where small electric currents are passed through the brain, intentionally triggering a brief seizure. Patients who have not responded to antidepressant medications may be candidates for ECT. ECT is FDA approved for treatment resistant depression.
DRUGKetamine
Ketamine is a medication that is used as a short acting anesthetic in pediatric and adult medicine. Subanesthetic (low) doses will be given to patients via infusion in order to assess whether it helps with depression symptoms in patients who have not responded to antidepressant therapy. Ketamine is not FDA approved for this indication and its effectiveness in treatment resistant depression has not been proven. Prior studies have indicated that subanesthetic doses of ketamine may be helpful for treatment resistant depression.
Sponsors
Patient-Centered Outcomes Research Institute
Bo Hu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Due to the nature of the study treatments it is not possible to blind patients or investigators.
Intervention model description
unblinded prospective randomized open-label
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent before any study related procedures are performed 2. Inpatients or outpatients referred by their providers for ECT treatment and eligible for ECT treatment 3. Males/females at least 21 years of age but no older than 75 years of age 4. Meet DSM-5 criteria for Major Depressive Episode as determined by both: A. a clinician's diagnostic evaluation and B. confirmed with the MINI International Neuropsychiatric Interview (MINI 7.0.2) 5. A current depressive episode that has lasted a minimum of 4 weeks 6. Meet all of the following criteria on symptom rating scales at screening: A. Montgomery Asberg Depression Rating Scale (MADRS) score \>20 B. Young Mania Rating Scale (YMRS) of ≤ 5 C. Montreal Cognitive Assessment (MoCA) of ≥18 7. Have had ≥2 adequate trials of antidepressants or augmentation strategies during their lifetime. An adequate trial is defined as 4 weeks of medication at the minimum FDA approved dose. This will be equal to a trial rating of 3 or more. 8. In the opinion of the investigator, the patient is willing and able to comply with scheduled visits, treatment plan, and other trial procedures for the duration of the study
Exclusion criteria
1. Meet DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, or pervasive developmental disorder 2. Meets any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Responses Based on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report Scale (QIDS-SR-16) | Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks | Response is defined as at least a 50% improvement in the QIDS-SR-16 scale from baseline to the End of Treatment visit. The End of Treatment visit will occur 3-5 weeks after the Baseline visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Responses Based on the Montgomery-Åsberg Rating Scale (MADRS) | Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks | The outcome measure was the percentage of responders at the end-of-treatment visit, defined as a ≥50% decrease in MADRS score from the baseline visit (i.e., first treatment visit) to the end-of-treatment visit (within 3 days of last treatment). |
Countries
United States
Participant flow
Recruitment details
From March 2017 - September 2022, outpatients or inpatients referred by their clinical providers to a site's ECT service for treatment were invited to participate in the study. Patients suffering from TRD who were interested in participation were enrolled after providing written informed consent.
Pre-assignment details
Of 2321 patients assessed, 436 met the inclusion criteria and were screened. 33 had screen failures and 403 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Electroconvulsive Therapy (ECT) Treatments will be given 3 times a week up to a total of 9 treatments over 3 - 5 weeks. Initial ECT treatment is Right Unilateral (RUL) ultra-brief pulse at 6X seizure threshold. Seizure threshold and dose can be increased per investigator and patient discretion.
electroconvulsive therapy (ECT): ECT is a procedure done under general anesthesia where small electric currents are passed through the brain, intentionally triggering a brief seizure. Patients who have not responded to antidepressant medications may be candidates for ECT. ECT is FDA approved for treatment resistant depression. | 203 |
| Ketamine Infusion Treatments will be given 2 times a week up to a total of 6 treatment over 3 - 5 weeks. Initial standard dose will be 0.5 mg/kg infusion over 40 min. The dose can be modified if clinically warranted per investigator and patient discretion.
Ketamine: Ketamine is a medication that is used as a short acting anesthetic in pediatric and adult medicine. Subanesthetic (low) doses will be given to patients via infusion in order to assess whether it helps with depression symptoms in patients who have not responded to antidepressant therapy. Ketamine is not FDA approved for this indication and its effectiveness in treatment resistant depression has not been proven. Prior studies have indicated that subanesthetic doses of ketamine may be helpful for treatment resistant depression. | 200 |
| Total | 403 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 31 | 4 |
Baseline characteristics
| Characteristic | Total | Electroconvulsive Therapy (ECT) | Ketamine Infusion |
|---|---|---|---|
| 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) | 18.1 units on a scale STANDARD_DEVIATION 4.1 | 18.2 units on a scale STANDARD_DEVIATION 4.2 | 17.9 units on a scale STANDARD_DEVIATION 4.1 |
| Age, Continuous | 46.3 years STANDARD_DEVIATION 14.4 | 47.1 years STANDARD_DEVIATION 14.1 | 45.6 years STANDARD_DEVIATION 14.8 |
| Age of onset of First Major Depression - yrs | 19.5 years STANDARD_DEVIATION 11.2 | 19.4 years STANDARD_DEVIATION 11 | 19.7 years STANDARD_DEVIATION 11.5 |
| Attempted Suicide | 157 Participants | 84 Participants | 73 Participants |
| BMI | 29.9 kg/m^2 STANDARD_DEVIATION 7.6 | 30.4 kg/m^2 STANDARD_DEVIATION 7.9 | 29.5 kg/m^2 STANDARD_DEVIATION 7.4 |
| Clinical Global Impression-Severity (CGI-S) scale | 5.1 units on a scale STANDARD_DEVIATION 0.6 | 5.2 units on a scale STANDARD_DEVIATION 0.6 | 5.0 units on a scale STANDARD_DEVIATION 0.6 |
| Duration of Current Episode - month | 24 months | 24 months | 24 months |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 11 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 368 Participants | 192 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Inpatient at first treatment | 44 Participants | 21 Participants | 23 Participants |
| Montgomery-Åsberg Rating Scale (MADRS) | 32.5 units on a scale STANDARD_DEVIATION 6.1 | 32.6 units on a scale STANDARD_DEVIATION 6 | 32.3 units on a scale STANDARD_DEVIATION 6.2 |
| Number of Past Major Depression Episodes | 5 Episodes | 5 Episodes | 5 Episodes |
| Number of Patients with Family History of Depression | 314 Participants | 160 Participants | 154 Participants |
| Previous ECT | 44 Participants | 21 Participants | 23 Participants |
| Previous Ketamine | 22 Participants | 8 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 7 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 12 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 355 Participants | 182 Participants | 173 Participants |
| Sex: Female, Male Female | 206 Participants | 100 Participants | 106 Participants |
| Sex: Female, Male Male | 197 Participants | 103 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 170 | 0 / 195 |
| other Total, other adverse events | 27 / 170 | 32 / 195 |
| serious Total, serious adverse events | 4 / 170 | 5 / 195 |
Outcome results
Primary
Number of Participants With Treatment Responses Based on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report Scale (QIDS-SR-16)
Response is defined as at least a 50% improvement in the QIDS-SR-16 scale from baseline to the End of Treatment visit. The End of Treatment visit will occur 3-5 weeks after the Baseline visit.
Time frame: Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks
Population: Modified Intention-to-treat Population (i.e., participants with at least one treatment and at least one follow-up measurement)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Electroconvulsive Therapy (ECT) | Number of Participants With Treatment Responses Based on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report Scale (QIDS-SR-16) | 70 Participants |
| Ketamine Infusion | Number of Participants With Treatment Responses Based on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report Scale (QIDS-SR-16) | 108 Participants |
p-value: <0.001The Farrington-Manning score test
Secondary
Number of Participants With Treatment Responses Based on the Montgomery-Åsberg Rating Scale (MADRS)
The outcome measure was the percentage of responders at the end-of-treatment visit, defined as a ≥50% decrease in MADRS score from the baseline visit (i.e., first treatment visit) to the end-of-treatment visit (within 3 days of last treatment).
Time frame: Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks
Population: Modified intention-to-treat population (i.e., participants with at least one treatment and at least one follow-up measurement). One participant in the ECT group had missing baseline MADRS and was further excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Electroconvulsive Therapy (ECT) | Number of Participants With Treatment Responses Based on the Montgomery-Åsberg Rating Scale (MADRS) | 70 Participants |
| Ketamine Infusion | Number of Participants With Treatment Responses Based on the Montgomery-Åsberg Rating Scale (MADRS) | 99 Participants |