Optimizing Electroconvulsive Therapy for Depression

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT00045916
First received: September 13, 2002
Last updated: August 9, 2013
Last verified: October 2008
  Purpose

This study will evaluate the effectiveness of electroconvulsive therapy (ECT) administered with medication for the treatment of a major depressive episode (unipolar or bipolar) and will compare two types of ECT.


Condition Intervention Phase
Depression
Depressive Disorder
Bipolar Disorder
Procedure: High dosage electroconvulsive therapy
Drug: Nortriptyline
Drug: Venlafaxine
Drug: Lithium
Procedure: Low dosage electroconvulsive therapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Optimization of Electroconvulsive Therapy

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Neurocognitive battery [ Time Frame: Measured at baseline and at 2 and 6 months after the acute ECT course ] [ Designated as safety issue: Yes ]
  • Clinical evaluations, side effect evaluations, and blood level determinations [ Time Frame: Measured weekly for the first month, every 2 weeks until Week 12, and every 4 weeks for the remaining 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Memory function [ Time Frame: Measured before and after ECT ] [ Designated as safety issue: Yes ]

Enrollment: 340
Study Start Date: February 2001
Study Completion Date: December 2006
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High dosage ECT + nortriptyline
Participants will receive nortriptyline and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment.
Procedure: High dosage electroconvulsive therapy
Participants will receive high dosage right unilateral ECT at six times the seizure threshold.
Drug: Nortriptyline
Participants will receive nortriptyline.
Drug: Lithium
Participants will receive lithium.
Experimental: High dosage ECT + venlafaxine
Participants will receive venlafaxine and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment.
Procedure: High dosage electroconvulsive therapy
Participants will receive high dosage right unilateral ECT at six times the seizure threshold.
Drug: Venlafaxine
Participants will receive venlafaxine.
Drug: Lithium
Participants will receive lithium.
Placebo Comparator: High dosage ECT + placebo
Participants will receive placebo and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment weeks.
Procedure: High dosage electroconvulsive therapy
Participants will receive high dosage right unilateral ECT at six times the seizure threshold.
Drug: Lithium
Participants will receive lithium.
Experimental: Low dosage ECT + nortriptyline
Participants will receive nortriptyline and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment.
Drug: Nortriptyline
Participants will receive nortriptyline.
Drug: Lithium
Participants will receive lithium.
Procedure: Low dosage electroconvulsive therapy
Participants will receive low dosage bilateral ECT at one and a half times the seizure threshold.
Experimental: Low dosage ECT + venlafaxine
Participants will receive venlafaxine and low dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment.
Drug: Venlafaxine
Participants will receive venlafaxine.
Drug: Lithium
Participants will receive lithium.
Procedure: Low dosage electroconvulsive therapy
Participants will receive low dosage bilateral ECT at one and a half times the seizure threshold.
Experimental: Low dosage ECT + placebo
Participants will receive placebo and low dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment weeks.
Drug: Lithium
Participants will receive lithium.
Procedure: Low dosage electroconvulsive therapy
Participants will receive low dosage bilateral ECT at one and a half times the seizure threshold.

Detailed Description:

This study addresses 2 issues in the optimization of ECT in patients with major depression: whether patients treated with ECT should receive concurrent treatment with antidepressant medications, and the relative efficacy and side effects of high dosage right unilateral (RUL) ECT compared to low dosage bilateral (BL) ECT.

This study has 2 phases. In Phase I, patients are randomized to receive nortriptyline, venlafaxine (Effexor), or placebo while they simultaneously receive either high dosage RUL ECT or low dosage BL ECT. Patients have an electrocardiogram (EKG), a chest x-ray, medical and neurological examinations, and blood tests. Memory function is assessed before and after ECT. Whenever feasible, patients are withdrawn from all prior psychotropic medication before the start of ECT. ECT is administered 3 times per week to inpatients and twice a week to outpatients. Patients continue ECT until they are asymptomatic or until there is a plateau in improvement over 2 treatments.

Patients who respond to ECT enter Phase II and add lithium to either nortriptyline or venlafaxine within 1-3 days of the last ECT. Clinical and side effect evaluations and blood level determinations are conducted weekly for the first month, every 2 weeks until Week 12, and every 4 weeks for the remaining 12 weeks. Following any indication of relapse, patients are monitored more intensively and are re-evaluated within 1 week. The neurocognitive battery is readministered to all patients at 2 and 6 months after the acute ECT course, regardless of ECT clinical outcome.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Major depressive episode (unipolar or bipolar)
  • Pre-ECT score of 20 or higher on Hamilton Rating Scale for Depression
  • Able to withdraw psychotropic drugs (up to 3 mg/day lorazepam allowed)
  • ECT indicated

Exclusion Criteria:

  • Schizophrenia, schizoaffective disorder, or other psychosis
  • Amnestic disorder, dementia, or delirium
  • Pregnancy
  • Epilepsy
  • Current alcohol or substance abuse or dependence
  • CNS disease or brain injury not associated with psychotropic drug exposure
  • ECT in the past 6 months
  • Medical contraindication for treatment with either nortriptyline or venlafaxine, including allergy to amitriptyline, nortriptyline, or venlafaxine; narrow angle glaucoma; sinus node disease; bundle branch disease; myocardial infarction; coronary artery bypass or angioplasty; or angina
  • Type I antiarrhythmic medication
  • Supine blood pressure >= 170 mmHg systolic or >= 105 mmHg diastolic at 3 readings over 2 days
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045916

Locations
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
New York State Psychiatric Institute at Columbia University
New York, New York, United States, 10032
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27103
United States, Pennsylvania
Western Psychiatric Institute and Clinic
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Study Chair: Harold A. Sackeim, PhD New York State Psychiatric Institute and Columbia University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00045916     History of Changes
Other Study ID Numbers: #3891, R01MH061609, DSIR 83-ATSO
Study First Received: September 13, 2002
Last Updated: August 9, 2013
Health Authority: United States: Federal Government

Keywords provided by New York State Psychiatric Institute:
Electroconvulsive therapy
Antidepressive Agents

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Lithium Carbonate
Nortriptyline
Venlafaxine
Lithium
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Antimanic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Antidepressive Agents, Tricyclic
Serotonin Uptake Inhibitors
Serotonin Agents

ClinicalTrials.gov processed this record on July 24, 2014