Optimizing Electroconvulsive Therapy for Depression

Study Overview
=================
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.

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 Whenever feasible, patients are withdrawn from all prior psychotropic medication before the start of ECT.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

Official Title
-----------------
Optimization of Electroconvulsive Therapy

Conditions
-----------------
Depression, Depressive Disorder, Bipolar Disorder

Intervention / Treatment
-----------------
* Procedure: High dosage electroconvulsive therapy
* Drug: Nortriptyline
* Drug: Venlafaxine
* Drug: Lithium
* Procedure: Low dosage electroconvulsive therapy


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dosage ECT + nortriptyline<br>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<br>* Participants will receive high dosage right unilateral ECT at six times the seizure threshold.<br>Drug: Nortriptyline<br>* Participants will receive nortriptyline.<br>Drug: Lithium<br>* Participants will receive lithium.<br>|
| Experimental: High dosage ECT + venlafaxine<br>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<br>* Participants will receive high dosage right unilateral ECT at six times the seizure threshold.<br>Drug: Venlafaxine<br>* Participants will receive venlafaxine.<br>Drug: Lithium<br>* Participants will receive lithium.<br>|
| Placebo Comparator: High dosage ECT + placebo<br>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<br>* Participants will receive high dosage right unilateral ECT at six times the seizure threshold.<br>Drug: Lithium<br>* Participants will receive lithium.<br>|
| Experimental: Low dosage ECT + nortriptyline<br>Participants will receive nortriptyline and high dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment. | Drug: Nortriptyline<br>* Participants will receive nortriptyline.<br>Drug: Lithium<br>* Participants will receive lithium.<br>Procedure: Low dosage electroconvulsive therapy<br>* Participants will receive low dosage bilateral ECT at one and a half times the seizure threshold.<br>|
| Experimental: Low dosage ECT + venlafaxine<br>Participants will receive venlafaxine and low dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment. | Drug: Venlafaxine<br>* Participants will receive venlafaxine.<br>Drug: Lithium<br>* Participants will receive lithium.<br>Procedure: Low dosage electroconvulsive therapy<br>* Participants will receive low dosage bilateral ECT at one and a half times the seizure threshold.<br>|
| Experimental: Low dosage ECT + placebo<br>Participants will receive placebo and low dosage ECT. If the ECT is effective participants will receive lithium after ECT treatment weeks. | Drug: Lithium<br>* Participants will receive lithium.<br>Procedure: Low dosage electroconvulsive therapy<br>* Participants will receive low dosage bilateral ECT at one and a half times the seizure threshold.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Memory function |  | Measured before and after ECT | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Electroconvulsive therapy, Antidepressive Agents