Nonconvulsive Electrotherapy: a Proof-of-concept Trial
Condition: Depressive Disorder; Bipolar Disorder; Schizoaffective Disorder
MeSH terms: Depressive Disorder; Bipolar Disorder; Psychotic Disorders
Intervention: Nonconvulsive electrotherapy
Intervention description: An electrical stimulus will be given as in electroconvulsive therapy (ECT)using bifrontal electrode placement and a Thymatron System IV device; however, the device will be set at a lower energy level that is 12.5%(1/8) of the expected energy needed to induce a seizure rather than at an energy level that is at or above the seizure threshold.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: electroconvulsive therapy; seizure; nonconvulsive; subconvulsive; major depression; bipolar disorder

Summary:

      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.
    

Eligibility criteria:

        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.