Optimizing Electroconvulsive Therapy for Depression

Sponsor

New York State Psychiatric Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00045916

Collaborator

National Institute of Mental Health (NIMH) (NIH)

340

Enrollment

Locations

Arms

69.9

Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Depression Depressive Disorder Bipolar Disorder	Procedure: High dosage electroconvulsive therapy Drug: Nortriptyline Drug: Venlafaxine Drug: Lithium Procedure: Low dosage electroconvulsive therapy	Phase 4

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 Whenever feasible, patients are withdrawn from all prior psychotropic medication before the start of ECT.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.

Study Design

Study Type:

Interventional

Actual Enrollment :

340 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Optimization of Electroconvulsive Therapy

Study Start Date :

Feb 1, 2001

Actual Primary Completion Date :

Dec 1, 2006

Actual Study Completion Date :

Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

Neurocognitive battery [Measured at baseline and at 2 and 6 months after the acute ECT course]
Clinical evaluations, side effect evaluations, and blood level determinations [Measured weekly for the first month, every 2 weeks until Week 12, and every 4 weeks for the remaining 12 weeks]

Secondary Outcome Measures

Memory function [Measured before and after ECT]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Washington University	St. Louis	Missouri	United States	63110
2	New York State Psychiatric Institute at Columbia University	New York	New York	United States	10032
3	Wake Forest University	Winston-Salem	North Carolina	United States	27103
4	Western Psychiatric Institute and Clinic	Pittsburgh	Pennsylvania	United States	15213