Major Depression, Bipolar Depression
Conditions
Keywords
depression, electroconvulsive therapy, ketamine, antidepressant
Brief summary
The primary objectives of this study are to investigate the potential for ketamine anesthesia to increase the antidepressant efficacy of Electroconvulsive therapy (ECT) and to decrease acute ECT-induced adverse cognitive effects.
Detailed description
Electroconvulsive therapy (ECT) is one of the most robust antidepressant treatments available. However, there is the potential for significant acute and longer term adverse cognitive effects with ECT and the antidepressant response requires multiple treatment sessions, increasing risk of adverse effects. Further, antidepressant response to ECT is often less than maximal and relapse is common. Growing preclinical and clinical evidence of the rapid-acting antidepressant properties of the anesthetic agent ketamine suggests the use of ketamine anesthesia as a strategy to increase rate of response and shorten treatment course in the administration of ECT. In addition, preclinical and clinical evidence suggests the potential of ketamine to decrease the adverse cognitive effects associated with ECT. The investigators propose a pilot study to measure both acute therapeutic efficacy and cognitive side effects of ECT using ketamine compared to methohexital in depressed patients. The investigators will also explore other parameters of ECT such as seizure duration and morphology, as well as hemodynamic and behavioral changes.
Interventions
DRUGKetamine
Ketamine 1-2 mg/kg IV as indicated for ECT
DRUGMethohexital
Methohexital 1 mg/kg IV as indicated for ECT
Sponsors
James Murrough
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients: 18 to 59 years 2. Women of childbearing potential must agree to use a medically accepted means of contraception for the duration of the study 3. DSM IV MINI diagnosis of major depressive episode (MDD), unipolar or bipolar 4. Pretreatment 24-item Hamilton Rating Scale for Depression score \> 21 5. ECT is clinically indicated 6. Patient has the capacity to provide informed consent.
Exclusion criteria
1. DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or mental retardation 2. Current primary diagnosis of anxiety disorder, obsessive- compulsive disorder, or eating disorder that precedes the onset of the current episode of depression 3. Current diagnosis of delirium, dementia, or amnestic disorder 4. Baseline Mini Mental State Exam (MMSE) score \< 24 and a total score falling two standard deviations below the age- and education-adjusted mean 5. Any active general medical condition or CNS disease which can affect cognition or response to treatment 6. Current (within the past three months) diagnosis of active substance dependence, or active substance abuse within the past week 7. Lifetime history of ketamine or PCP abuse or dependence 8. ECT within three months 9. The presence of any known or suspected contraindication to methohexital or ketamine including but not limited to known allergic reactions to these agents, uncontrolled hypertension arrhythmia severe coronary artery disease and porphyria 10. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Rating Scale for Depression-24 (HRSD24) | Change from beginning of ECT treatment to end; on average 3 weeks | The HDRS-24 is used to rate depressive symptoms. This instrument is considered one of the gold standard clinician-rated instruments for depressive symptoms. We have established procedures for the maintenance of inter-rater reliability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR) | Change from beginning of ECT treatment to end; on average 3 weeks | The QIDS-SR is a 16-item self-rated instrument designed to assess the severity of depressive symptoms present in the past seven days (Rush et al 2003). The 16 items cover the nine symptom domains of major depression, and are rated on a scale of 0-3. Total score ranges from 0 to 27, with ranges of 0-5 (normal), 6-10 (mild), 11-15 (moderate), 16-20 (moderate to severe), and 21+ (severe). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Participants receiving ECT for depression will be randomized 1:1 to either ketamine (experimental condition) or methohexital (standard anesthetic). | 2 |
| Methohexital Participants receiving ECT for depression will be randomized 1:1 to either ketamine (experimental condition) or methohexital (standard anesthetic). | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Ketamine | Methohexital | Total |
|---|---|---|---|
| Age Continuous | 53 years STANDARD_DEVIATION 5.6 | 50 years STANDARD_DEVIATION 0 | 50 years STANDARD_DEVIATION 4.3 |
| Region of Enrollment United States | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Hamilton Rating Scale for Depression-24 (HRSD24)
The HDRS-24 is used to rate depressive symptoms. This instrument is considered one of the gold standard clinician-rated instruments for depressive symptoms. We have established procedures for the maintenance of inter-rater reliability.
Time frame: Change from beginning of ECT treatment to end; on average 3 weeks
Secondary
Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR)
The QIDS-SR is a 16-item self-rated instrument designed to assess the severity of depressive symptoms present in the past seven days (Rush et al 2003). The 16 items cover the nine symptom domains of major depression, and are rated on a scale of 0-3. Total score ranges from 0 to 27, with ranges of 0-5 (normal), 6-10 (mild), 11-15 (moderate), 16-20 (moderate to severe), and 21+ (severe).
Time frame: Change from beginning of ECT treatment to end; on average 3 weeks