Optimizing Electroconvulsive Therapy for Depression - Full Text View

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00045916

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 IV

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:

MedlinePlus related topics: Antidepressants Bipolar Disorder Depression

Drug Information available for: Venlafaxine Nortriptyline Venlafaxine hydrochloride Lithium carbonate Nortriptyline hydrochloride Lithium citrate

U.S. FDA Resources

Further study details as provided by National Institute of Mental Health (NIMH):

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

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

National Institute of Mental Health (NIMH)

Investigators

Study Chair:

Harold A. Sackeim, PhD

New York State Psychiatric Institute and Columbia University

More Information

Publications:

Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann JJ, Pettinati HM, Greenberg RM, Crowe RR, Cooper TB, Prudic J. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA. 2001 Mar 14;285(10):1299-307.

Sackeim HA, Prudic J, Devanand DP, Nobler MS, Lisanby SH, Peyser S, Fitzsimons L, Moody BJ, Clark J. A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry. 2000 May;57(5):425-34.

McCall WV, Reboussin DM, Weiner RD, Sackeim HA. Titrated moderately suprathreshold vs fixed high-dose right unilateral electroconvulsive therapy: acute antidepressant and cognitive effects. Arch Gen Psychiatry. 2000 May;57(5):438-44.

Responsible Party:	Harold A. Sackeim, PhD, New York State Psychiatric Institute and Columbia University
ClinicalTrials.gov Identifier:	NCT00045916 History of Changes
Other Study ID Numbers:	R01 MH61609, DSIR 83-ATSO
Study First Received:	September 13, 2002
Last Updated:	October 10, 2008
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

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 February 12, 2012