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

Ketamine Anesthesia to Enhance Efficacy and Tolerability of Electroconvulsive Therapy in Patients With Unipolar or Bipolar Depression

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.

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.

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