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

Not Applicable

Terminated

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.

Recruitment & Eligibility

Inclusion Criteria

Male or female patients: 18 to 59 years
Women of childbearing potential must agree to use a medically accepted means of contraception for the duration of the study
DSM IV MINI diagnosis of major depressive episode (MDD), unipolar or bipolar
Pretreatment 24-item Hamilton Rating Scale for Depression score > 21
ECT is clinically indicated
Patient has the capacity to provide informed consent.

Exclusion Criteria

DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or mental retardation
Current primary diagnosis of anxiety disorder, obsessive- compulsive disorder, or eating disorder that precedes the onset of the current episode of depression
Current diagnosis of delirium, dementia, or amnestic disorder
Baseline Mini Mental State Exam (MMSE) score < 24 and a total score falling two standard deviations below the age- and education-adjusted mean
Any active general medical condition or CNS disease which can affect cognition or response to treatment
Current (within the past three months) diagnosis of active substance dependence, or active substance abuse within the past week
Lifetime history of ketamine or PCP abuse or dependence
ECT within three months
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
Pregnancy

Arm && Interventions

Group	Intervention	Description
Ketamine	Ketamine	Participants receiving ECT for depression will be randomized 1:1 to either ketamine (experimental condition) or methohexital (standard anesthetic).
Methohexital	Methohexital	Participants receiving ECT for depression will be randomized 1:1 to either ketamine (experimental condition) or methohexital (standard anesthetic).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).