Symposium 3. Continuation and Maintenance Therapy After ECT: Chair: Harold A. Sackeim Ph.D

Continuation Pharmacology in the Prevention of Relapse Following ECT. Joan Prudic. Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY, U.S.A.

Objective:

To determine the efficacy of continuation pharmacotherapy with nortriptyline or combination nortriptyline and lithium carbonate in preventing post-ECT relapse.

Background:

Electroconvulsive therapy is highly effective in the treatment of major depression, but naturalistic studies show a high rate of relapse.

Method:

A randomized, double-blind, placebo-controlled trial comparing the two conditions with placebo was conducted; 84 patients were randomized to one of the three conditions.

Results:

The lithium-nortriptyline combination had a marked advantage in time to relapse, superior to both placebo and nortriptyline alone. Over 6 months, the relapse rates were: placebo, 84.0%; nortriptyline, 6.00%; nortriptyline-lithium, 39.1%. All but one relapse with the combination occurred in the first 5 weeks. With the other two conditions, relapse continued throughout the study period.

Conclusions:

Without active treatment the vast majority of remitted patients treated with ECT will relapse within 6 months. The combination treatment with nortriptyline-lithium is most effective, but relapse does occur in the first month of continuation therapy. Alternative strategies are needed.

Continuation ECT versus Pharmacotherapy-The CORE Trial. * Charles H. Kellner, †M. Husain, ‡T. Rummans, §G. Petrides, §M. Fink, * R. Knapp, ‡G. Smith, * H. Bernstein, * M. Mueller. *Department of Psychiatry & Behavioral Sciences, Medical University of South Carolina, Charleston, SC; †University of Texas Southwestern Medical Center, Dallas, TX; ‡Mayo Foundation, Rochester, MN; §Hillside Hospital/Long Island Jewish Medical Center, New York, NY, U.S.A.

Objective:

To describe the ongoing multisite, NIH-funded CORE (Consortium for Research in ECT: Medical University of South Carolina, Hillside Hospital/Long Island Jewish Medical Center, Mayo Clinic, University of Texas Southwestern Medical Center) study Continuation ECT versus Pharmacotherapy: Safety and Efficacy.

Background:

Clinical evidence has long suggested a role for continuation/maintenance ECT in the prophylactic treatment of serious depressive illness. However, no controlled studies have directly compared continuation/maintenance ECT with pharmacotherapy.

Design/Methods:

This is a prospective, multicenter, random assignment, single blind study comparing continuation ECT and the combination nortriptyline and lithium for the prevention of depressive relapse. The study population consist of unipolar patients with MDD who have responded to acute phase ECT during the index depressive episode. The acute phase treatment with ECT is termed Phase 1. Phase 2 designates the random assignment continuation phase of the trial. The ECT schedule in Phase 2 provides for weekly ECT ×4, biweekly ×4, and monthly ×2 for a total of 10 ECTs over 5 months. Patients are monitored for response using the Hamilton Depression Rating Scale (HAM-D) and are given a comprehensive neurophysiological test battery at specified time points in both phases.

Results:

357 patients have been entered into Phase 1 and 150 randomized into Phase 2. The average age of the sample was 55.6 years (±17.3); 32.2% of the study sample was psychotic. The baseline HAM-D was 34.9 (±8.0) and the HAM-D at the end of Phase 1 was 10.8 (±9.0). 68.9% of patients remitted (last two HAM-D 10). Phase 2 results have yet to be unblinded. Overall, the combined relapse rate for the two study groups is 25.3%.

Conclusions:

We have confirmed the speed and efficacy of ECT as an acute treatment for major depression. The results of the randomized phase of our trial will provide the first controlled data on the efficacy and tolerability of continuation ECT.

A Naturalistic Study of Maintenance ECT: Implications for Optimizing the Inter-Treatment Interval. Andrew D. Krystal, Tracey Holsinger, Richard D. Weiner, David C. Steffens, C. Edward Coffey. Duke University Medical Center, Durham, NC, U.S.A.

Objective:

To understand how to better administer maintenance ECT.

Background:

Uncertainty exists about how to optimize the administration of maintenance ECT. A particular need is better understanding of the optimal interval between treatments. As a result, we carried out a naturalistic study of clinical maintenance ECT in which the interval between treatment varied (nonsystematically) among the subjects so that we were able to assess relationships among the interval between treatments and the effectiveness of maintenance ECT in preventing relapse.

Design/Methods:

All patients who received maintenance ECT at Duke University Medical Center for unipolar or bipolar depression from 1988 to June 2000 were included in this retrospective analysis. Each patient had responded to index ECT (2.25 times threshold unilateral ECT or 1.5 times threshold bilateral ECT). Relapse was defined as a MADRS score of greater than 14 and at least a 50% increase in MADRS score from the end of the index ECT course. Maintenance ECT was administered according to a protocol in which the interval between treatments was gradually lengthened over time. The interval between treatments was decreased, if depressive symptoms increased, and was increased if cognitive side effects increased, at the discretion of the attending ECT physician. Patients remained in the maintenance ECT course for an average of 191 days (range: 13-1,107).

Results:

Of the 110 patients studied, 54 (49%) met relapse criteria at some point during the maintenance ECT course. Younger age increased the risk of relapse but not electrode placement or other historical/demographic factors. For the 54 patients who met relapse criteria, a decrease in the interval between treatments to 1 week or less resulted in resolution of the relapse in 32 (59%). In all, 80% of the patients (88/110) ended their maintenance course meeting responder criteria.

Conclusions:

Our clinical experience indicates that the inter-treatment interval has a substantial effect on the efficacy of maintenance ECT. While roughly one-half of patients who receive maintenance ECT with a gradually increasing inter-treatment interval protocol will experience a relapse, responding to the relapse with a decrease in the interval to 1 week or less leads to resolution of the relapse in nearly 60% of subjects. This intervention allowed 80% of subjects to end their course as responders and appears to be a highly effective maintenance ECT strategy. Further work is needed to optimize the inter-treatment interval schedule for maintenance ECT.