Depression
Conditions
Keywords
Depression, Electroconvulsive therapy, Ketamine, Methohexital
Brief summary
Does the use of ketamine as the anesthetic medication in electroconvulsive therapy (ECT) accelerate the antidepressant effect of ECT? The study hypothesis was that depressed subjects receiving ECT with ketamine as the anesthetic agent would demonstrate a faster rate of improvement, defined as lower depression ratings after the second ECT than depressed patients receiving ECT with the usual anesthetic agent.
Detailed description
There are several drugs available to induce anesthesia for electroconvulsive therapy (ECT), a psychiatric treatment for major depressive illness. The most commonly utilized of these include methohexital, thiopental, etomidate, and propofol. Recently, there has been interest in the use of ketamine in sub-anesthetic doses to treat major depressive illness. In this randomized, blinded trial, depressed subjects scheduled to be treated with ECT were anesthetized with either ketamine or methohexital at doses of approximately 1.0 mg/kg for each drug. Patients received the same drug for up to six of their ECT treatments. Outcome measures included assessments of depressive severity, cognition, post-anesthesia side effects, and hemodynamics. Subjects were to be followed with as long as they were receiving inpatient ECT treatments. The number of treatments was determined entirely by their primary psychiatric team, also blind to anesthetic, as per usual care. In other words, this study did not determine when to terminate the ECT course.
Interventions
DRUGKetamine
Subjects were dosed with approximately 1.0 mg/kg, using ketamine as anesthetic.
DRUGmethohexital
Subjects were dosed with approximately 1.0 mg/kg, using methohexital as anesthetic.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of depression, either unipolar or bipolar * Subjects receiving ECT at the Mayo Clinic
Exclusion criteria
* Subjects not giving their own consent to ECT * Subjects with schizophrenia, schizoaffective disorder, or dementia * Subjects diagnosed with a major neurological disorder such as epilepsy, Parkinson disease, multiple sclerosis, or a neurodegenerative dementia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Depression Rating Using the Hospital Anxiety and Depression Scale (HADS) | Baseline and after every second treatment for 7 treatments | The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 42 (severe symptoms) for either anxiety or depression. The questionnaire was administered to the subjects prior to the first treatment, the morning of the third treatment, the morning of the fifth treatment, and the morning of the seventh treatment. For subjects whose treatment series ws cancelled prior to a scheduled next administration of the rating scale, every effort was made to administer them 2 days after the last treatment. Means are reported overall across all treatments; p-values also take into account variability across treatments and within subject. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Depression Rating Using the Patient Health Questionnaire-9 (PHQ-9) | Baseline and after every second treatment for 7 treatments | The PHQ-9 is the nine item depression scale of the Patient Health Questionnaire. The PHQ-9 is based directly on the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual Fourth Edition (DSM-IV). Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 27 (severe symptoms) for depression. The questionnaire was administered to the subjects prior to the first treatment, the morning of the third treatment, the morning of the fifth treatment, and the morning of the seventh treatment. For subjects whos treatment series ws cancelled prior to a scheduled next administration of the rating scale, every effort was mde to administer them 2 days after the last treatment. Means are reported overall across all treatments; p-values also take into account variability across treatments and within subject. |
| Mean Post Anesthesia Recovery Side Effects | Time of discharge from recovery after ECT for each treatment, approximately 30 minutes after the end of the seizure | Post anesthesia recovery side effects were assessed at the time of discharge from recovery with five patient self-report items: nausea, headache, myalgia, visual disturbance, and confusion. These were rated by the patients on a four point scale (0, 1, 2, 3) - absent, mild, moderate, severe. This means that for each item a subject could score between 0 (no symptoms) and 3 (severe symptoms). Also, degree of recovery room agitation was rated by the nurse on a similar four point scale. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled at Mayo Clinic, Rochester, Minnesota.
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Subjects were dosed with approximately 1.0 mg/kg, using ketamine as anesthetic prior to electroconvulsive therapy (ECT). | 21 |
| Methohexital Subjects were dosed with approximately 1.0 mg/kg, using methohexital as anesthetic prior to electroconvulsive therapy. | 17 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Ketamine | Methohexital | Total |
|---|---|---|---|
| Age Continuous | 46.95 years STANDARD_DEVIATION 13.17 | 48.65 years STANDARD_DEVIATION 7.2 | 47.7 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment United States | 21 participants | 17 participants | 38 participants |
| Sex: Female, Male Female | 16 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 17 |
| serious Total, serious adverse events | 0 / 21 | 0 / 17 |
Outcome results
Primary
Mean Depression Rating Using the Hospital Anxiety and Depression Scale (HADS)
The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 42 (severe symptoms) for either anxiety or depression. The questionnaire was administered to the subjects prior to the first treatment, the morning of the third treatment, the morning of the fifth treatment, and the morning of the seventh treatment. For subjects whose treatment series ws cancelled prior to a scheduled next administration of the rating scale, every effort was made to administer them 2 days after the last treatment. Means are reported overall across all treatments; p-values also take into account variability across treatments and within subject.
Time frame: Baseline and after every second treatment for 7 treatments
Population: Analysis was intent to treat; for the ketamine arm there were 54 observations, for the methohexital arm there were 55 observations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Mean Depression Rating Using the Hospital Anxiety and Depression Scale (HADS) | 22.08 units on a scale | Standard Deviation 8.11 |
| Methohexital | Mean Depression Rating Using the Hospital Anxiety and Depression Scale (HADS) | 24.45 units on a scale | Standard Deviation 7.7 |
Comparison: P-values take into account variability across treatments and within subject.p-value: 0.171t-test, 2 sided
Secondary
Mean Depression Rating Using the Patient Health Questionnaire-9 (PHQ-9)
The PHQ-9 is the nine item depression scale of the Patient Health Questionnaire. The PHQ-9 is based directly on the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual Fourth Edition (DSM-IV). Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 27 (severe symptoms) for depression. The questionnaire was administered to the subjects prior to the first treatment, the morning of the third treatment, the morning of the fifth treatment, and the morning of the seventh treatment. For subjects whos treatment series ws cancelled prior to a scheduled next administration of the rating scale, every effort was mde to administer them 2 days after the last treatment. Means are reported overall across all treatments; p-values also take into account variability across treatments and within subject.
Time frame: Baseline and after every second treatment for 7 treatments
Population: Analysis was intent to treat; for the ketamine arm there were 65 observations, for the methohexital arm there were 63 observations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Mean Depression Rating Using the Patient Health Questionnaire-9 (PHQ-9) | 15.98 units on a scale | Standard Deviation 7.54 |
| Methohexital | Mean Depression Rating Using the Patient Health Questionnaire-9 (PHQ-9) | 17.57 units on a scale | Standard Deviation 6.96 |
Comparison: P-values take into account variability across treatments and within subject.p-value: 0.258t-test, 2 sided
Secondary
Mean Post Anesthesia Recovery Side Effects
Post anesthesia recovery side effects were assessed at the time of discharge from recovery with five patient self-report items: nausea, headache, myalgia, visual disturbance, and confusion. These were rated by the patients on a four point scale (0, 1, 2, 3) - absent, mild, moderate, severe. This means that for each item a subject could score between 0 (no symptoms) and 3 (severe symptoms). Also, degree of recovery room agitation was rated by the nurse on a similar four point scale.
Time frame: Time of discharge from recovery after ECT for each treatment, approximately 30 minutes after the end of the seizure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Mean Post Anesthesia Recovery Side Effects | Headache | 0.29 units on a scale | Standard Deviation 0.61 |
| Ketamine | Mean Post Anesthesia Recovery Side Effects | Visual Disturbance | 0.08 units on a scale | Standard Deviation 0.28 |
| Ketamine | Mean Post Anesthesia Recovery Side Effects | Nausea | 0.12 units on a scale | Standard Deviation 0.39 |
| Ketamine | Mean Post Anesthesia Recovery Side Effects | Confusion | 0.70 units on a scale | Standard Deviation 0.95 |
| Ketamine | Mean Post Anesthesia Recovery Side Effects | Myalgia | 0.07 units on a scale | Standard Deviation 0.3 |
| Ketamine | Mean Post Anesthesia Recovery Side Effects | Recovery Room Agitation | 0.07 units on a scale | Standard Deviation 0.26 |
| Methohexital | Mean Post Anesthesia Recovery Side Effects | Myalgia | 0.15 units on a scale | Standard Deviation 0.48 |
| Methohexital | Mean Post Anesthesia Recovery Side Effects | Nausea | 0.15 units on a scale | Standard Deviation 0.42 |
| Methohexital | Mean Post Anesthesia Recovery Side Effects | Headache | 0.35 units on a scale | Standard Deviation 0.67 |
| Methohexital | Mean Post Anesthesia Recovery Side Effects | Recovery Room Agitation | 0.09 units on a scale | Standard Deviation 0.36 |
| Methohexital | Mean Post Anesthesia Recovery Side Effects | Visual Disturbance | 0.01 units on a scale | Standard Deviation 0.11 |
| Methohexital | Mean Post Anesthesia Recovery Side Effects | Confusion | 0.30 units on a scale | Standard Deviation 0.53 |
Comparison: Comparison between groups for nauseap-value: 0.091t-test, 2 sided
Comparison: Comparison between groups for headachep-value: 0.763t-test, 2 sided
Comparison: Comparison between groups for myalgiap-value: 0.356t-test, 2 sided
Comparison: Comparison between groups for visual disturbancep-value: 0.093t-test, 2 sided
Comparison: Comparison between groups for confusionp-value: 0.003t-test, 2 sided
Comparison: Comparison between groups for recovery room agitationp-value: 0.86t-test, 2 sided