This study will compare four types of electroconvulsive therapy to determine if they differ in their effects on mood, thinking, brain activity, and biochemistry in people with major depressive disorder.

Major depressive disorder (MDD) is a serious condition that can interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were once pleasurable. Depression may occur only once in a lifetime, but usually occurs several times. There are several types of medications and therapies that have been successful in improving symptoms of depression. Electroconvulsive therapy (ECT) has been particularly successful in treating individuals whose depression is severe or life threatening or who cannot take antidepressant medication. In ECT, electrodes are placed at precise locations on the head to deliver electrical impulses. The stimulation causes a brief seizure within the brain. The person receiving ECT does not consciously experience the electrical stimulus and does not feel pain. This study will compare four types of ECT to determine if they differ in their effects on mood, thinking, brain activity, and biochemistry in people with MDD.

Participants in this double-blind study will be randomly assigned to receive one of four types of ECT. Treatments will occur three times a week for 2 to 6 weeks, depending on each participant's individual needs. All participants will stop taking any psychiatric medications at least 5 days before receiving ECT. Before beginning each ECT session, participants will be interviewed by study staff about their current psychiatric condition, any psychological problems they have had, any history of psychological problems in their families, their medical history, and their attitudes about receiving ECT. A family member may also be asked to participate in some interviews. In addition, before each treatment, monitoring sensors will be placed on each participant's head and other areas of the body and a blood pressure cuff will be placed on an arm. These devices will be used to monitor each participant's brain waves, heart, and blood pressure before, during, and after treatment.

Because ECT entails the use of general anesthesia, participants will not eat for at least 8 hours before each treatment. An intravenous catheter will be placed in participants' arms to administer the anesthesia and a muscle relaxant. Just before receiving ECT, participants will be asked to remember a set of information. Upon waking after treatment, participants will be asked to recall or recognize this material and complete a set of brief neuropsychological tasks. Electroencephalogram (EEG) tests (to measure electrical activity of the brain), transcranial magnetic stimulation (TMS) (to measure muscle activity), blood collection, and magnetic resonance imaging (MRI) tests (to image the inside of the body) will be performed at selected sessions and follow-up visits to assess outcomes. Follow-up interviews will be held via telephone every 2 weeks for 2 months post-treatment, and then monthly for the remainder of the year. Follow-up neuropsychological tests will also be administered at Months 2, 4, and 6 post-treatment.

Inclusion Criteria:

• Diagnosis of major depressive disorder
• Pretreatment score of at least 18 on the Hamilton Rating Scale for Depression
• Able to tolerate psychotropic washout and no psychotropic medication, other than lorazepam (up to 3 mg/d PRN), during the study
• Recommended to receive ECT

Exclusion Criteria:

• History of schizophrenia, schizoaffective disorder, other functional psychosis, or rapid cycling bipolar disorder
• Secondary diagnosis of a delirium, dementia, or amnestic disorder, or epilepsy
• Pregnant
• History of neurological illness other than conditions associated with psychotropic exposure (e.g., tardive dyskinesia)
• History of alcohol or substance abuse within the year prior to study entry
• History of ECT within the 6 months prior to study entry