This study involves pilot testing of a modified version of a proven treatment for mental illness. The treatment, electroconvulsive therapy (ECT) is used to treat more than 100,000 Americans yearly. ECT is the most effective treatment for major depression, a disorder that affects approximately 5 to 8 percent of the adult US population yearly. It is also an effective treatment for mania and mixed mood states associated with bipolar disorder and schizoaffective disorder.

The aim of ECT is to induce a seizure, which is thought to be responsible for both its therapeutic and its adverse cognitive effects. The proposed modification consists of reducing the ECT electrical stimulus dose below the amount necessary to induce seizures so that adverse cognitive effects, such as confusion and memory problems, are minimized.

The investigators intend to determine whether ECT-related cognitive impairment can be reduced without diminishing the therapeutic effect of ECT. In addition to distressing patients, ECT-related cognitive impairment has significant public health consequences. These include increased morbidity and mortality among severely ill individuals who refuse ECT due to concern over its adverse cognitive effects as well as increased falls among the elderly receiving ECT. Elderly patients are far more likely to receive ECT and are also more vulnerable to ECT-related cognitive impairment. They often require hospitalization for ECT and a longer hospital stay with greater spacing of treatments to minimize adverse cognitive effects.

The hypothesis driving this research is that electrical brain stimulation applied in the same manner as standard ECT, but at a lower dose, can have therapeutic effects and fewer adverse cognitive effects without inducing seizures. This hypothesis is based on the following: 1) the investigators clinical experience of patients who have improved with ECT despite having only one or no seizure, 2) animal studies showing that electrical brain stimulation can induce antidepressant like effects in animals without inducing seizures, 3) reports from the 1950s that "subconvulsive" and "nonconvulsive" electrotherapy was effective for some patients, and 4) the recent approval by the US Food and Drug Administration of the use of transcranial magnetic stimulation --a technique that uses a magnet to induce an electrical current in the brain without inducing seizures--for treatment of medication resistant major depression.

The primary aim of the research is to conduct a proof of concept, open trial investigating the therapeutic efficacy and safety of nonconvulsive electrotherapy (NET). The investigators plan to enroll 16 subjects, which is the minimum number of subjects needed to show that the therapeutic effect of NET is better than would be expected of placebo. If the investigators show that the therapeutic effect of NET exceeds that expected of placebo and does not induce significant cognitive impairment, then the investigators will go on to propose a blind, randomized, controlled clinical trial that more definitively tests the investigators' hypothesis. The investigators would use the information gathered from the pilot trial to estimate the number of subjects needed to definitively test the efficacy and safety of NET.

The secondary aim of the study is to find out whether NET affects blood levels of brain-derived neurotrophic factor (BDNF). BDNF is a substance that is important to the nervous system and may be related to how treatments like ECT or possibly NET improve symptoms. The investigators would draw a blood sample before and after NET treatment to assess this.

Inclusion Criteria:

1. Men and women, aged 18 years and older meeting structured clinical interview for the DSM IV (SCID) criteria for unipolar major depressive disorder, bipolar disorder, or schizoaffective disorder.
2. Subjects of child-bearing potential must agree to have a pregnancy test prior to enrollment and agree to use a reliable method of birth-control during the study.
3. Willingness and ability to provide informed consent as determined by satisfactorily completing the study-specific Evaluation to Sign Consent Form Test.
4. Baseline score ≥ 16 on the 21-item version of the Hamilton Depression Rating Scale (HAMD-21) for unipolar depression, the Bipolar Depression Rating Scale (BDRS) for bipolar depression, or the Young Mania rating scale (YMRS) for mania.
5. Willingness to allow the Principal Investigator to discuss study participation with treating psychiatrist
6. Taking the same regimen of psychiatric medications with no changes for at least one month prior to NET treatment and willingness to not have any medication changes during NET treatment.
7. Currently an outpatient.
8. History of or currently refusing ECT due to experience of or anticipation of adverse effects.

Exclusion Criteria:

1. Pregnancy.
2. Use of any investigational drugs within 30 days of baseline or at any time during the study.
3. Ongoing substance abuse or dependence.
4. Current suicidal ideas.
5. Presence of any condition that would contraindicate ECT or bifrontal electrode placement.
6. Medical or neurologic condition etiologically related to mood disorder.
7. History of coronary artery disease or cardiac arrhythmia.
8. History of serious, potentially life-threatening reaction to anesthesia.
9. For individuals who need to have brain imaging, presence of metal in the body that would make a head MRI unsafe.
10. For individuals who need to have brain imaging, history of claustrophobia or anxiety associated with previous MRI.
11. Allergy or adverse reaction to methohexital or succinylcholine.
12. Epilepsy or seizure disorder.

4 years

Subjects each participated for 2-4 weeks over the 4 year total duration of study. Participants were queried for adverse events, defined as an unwelcome change in physical or mental status that required clinical assessment, prior to and following each treatment.