Use of Ketamine to Enhance Electroconvulsive Therapy (ECT) in Depression

• ClinicalTrials.gov Identifier: NCT01309581
• Recruitment Status: Terminated
• First Posted: March 7, 2011
• Results First Posted: August 30, 2013
• Last Update Posted: August 30, 2013
• Sponsor: James Murrough
• Information provided by (Responsible Party): James Murrough, Icahn School of Medicine at Mount Sinai

Tracking Information

• First Submitted Date: March 2, 2011
• First Posted Date: March 7, 2011
• Results First Submitted Date: November 7, 2012
• Results First Posted Date: August 30, 2013
• Last Update Posted Date: August 30, 2013
• Study Start Date: April 2010
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2011)

Hamilton Rating Scale for Depression-24 (HRSD24) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 29, 2013)

Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR) [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: March 4, 2011)

• Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR) [ Time Frame: 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).
• Brief Psychiatric Rating Scale (BPRS) [ Time Frame: Change from beginning of ECT treatment to end; on average 3 weeks ]
  The BPRS is used to assess acute behavioral changes during the infusions. Four key BPRS items for the positive (+) symptoms of psychosis will be used: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Three items representing the negative (-) symptoms of psychosis will also be used: blunted affect, emotional withdrawal, and motor retardation.
• Patient Rated Inventory of Side Effects (PRISE) [ Time Frame: Change from beginning of ECT treatment to end; on average 3 weeks ]
  The PRISE assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other). Each system will score 0 to 2 based on the severity of the complaints (0 = no side effect, 1 = tolerable side effect, 2 = distressing side effect) and the total score is calculated.
• Autobiographical Memory Interview (AMI) [ Time Frame: Change from beginning of ECT treatment to end; on average 3 weeks ]
• Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: Change from beginning of ECT treatment to end; on average 3 weeks ]
  The CADSS is used to measure dissociative effects during the infusions. The scale includes 19 questions and 8 observer ratings scored from 0 (not at all) to 4 (extremely). The CADSS measures impairment in body perception, environmental perception, time perception, memory impairment, and feelings of unreality.
• The Rey Auditory Verbal Learning Test (AVLT) [ Time Frame: Change from beginning of ECT treatment to end; on average 3 weeks ]
  This scale is brief and easy to administer and has been well-validated. Equivalent alternate forms are available

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Use of Ketamine to Enhance Electroconvulsive Therapy (ECT) in Depression
• Official Title: Ketamine Anesthesia to Enhance Efficacy and Tolerability of Electroconvulsive Therapy in Patients With Unipolar or Bipolar Depression
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Major Depression
• Bipolar Depression

Intervention

• Drug: Ketamine
  Ketamine 1-2 mg/kg IV as indicated for ECT
• Drug: Methohexital
  Methohexital 1 mg/kg IV as indicated for ECT

Study Arms

• Experimental: Ketamine
  Participants receiving ECT for depression will be randomized 1:1 to either ketamine (experimental condition) or methohexital (standard anesthetic).
  Intervention: Drug: Ketamine
• Active Comparator: Methohexital
  Participants receiving ECT for depression will be randomized 1:1 to either ketamine (experimental condition) or methohexital (standard anesthetic).
  Intervention: Drug: Methohexital

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 29, 2013): 3
• Original Estimated Enrollment (submitted: March 4, 2011): 24
• Actual Study Completion Date: October 2010
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01309581
• Other Study ID Numbers: GCO 09-2251; KETECT-MSSM-01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: James Murrough, Icahn School of Medicine at Mount Sinai
• Original Responsible Party: James Murrough, M.D., Mount Sinai School of Medicine
• Current Study Sponsor: James Murrough
• Original Study Sponsor: Murrough, James, M.D.
• Collaborators: Not Provided

Investigators

• Principal Investigator: James W Murrough, MD; Icahn School of Medicine at Mount Sinai

• PRS Account: Icahn School of Medicine at Mount Sinai
• Verification Date: July 2013