Optimizing Electroconvulsive Therapy for Depression

New York State Psychiatric Institute

Status and phase: Completed; Phase 4

Conditions: Bipolar Disorder; Depression; Depressive Disorder

Treatments: Procedure: High dosage electroconvulsive therapy; Drug: Venlafaxine; Drug: Lithium; Procedure: Low dosage electroconvulsive therapy; Drug: Nortriptyline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00045916

R01MH061609 (U.S. NIH Grant/Contract)

#3891

DSIR 83-ATSO

Details and patient eligibility

About

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.

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 Whenever feasible, patients are withdrawn from all prior psychotropic medication before the start of ECT.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

Enrollment: 340 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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340 participants in 6 patient groups, including a placebo group

High dosage ECT + nortriptyline

Experimental group

Description:

Participants will receive nortriptyline and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment.

Treatment:

Drug: Lithium

Procedure: High dosage electroconvulsive therapy

Drug: Nortriptyline

High dosage ECT + venlafaxine

Experimental group

Description:

Participants will receive venlafaxine and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment.

Treatment:

Drug: Venlafaxine

Drug: Lithium

Procedure: High dosage electroconvulsive therapy

High dosage ECT + placebo

Placebo Comparator group

Description:

Participants will receive placebo and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment weeks.

Treatment:

Drug: Lithium

Procedure: High dosage electroconvulsive therapy

Low dosage ECT + nortriptyline

Experimental group

Description:

Participants will receive nortriptyline and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment.

Treatment:

Procedure: Low dosage electroconvulsive therapy

Drug: Lithium

Drug: Nortriptyline

Low dosage ECT + venlafaxine

Experimental group

Description:

Participants will receive venlafaxine and low dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment.

Treatment:

Drug: Venlafaxine

Procedure: Low dosage electroconvulsive therapy

Drug: Lithium

Low dosage ECT + placebo

Experimental group

Description:

Participants will receive placebo and low dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment weeks.

Treatment:

Procedure: Low dosage electroconvulsive therapy

Drug: Lithium