ECT is highly effective and patients that receive this modality often present with severe forms of major depression. Early relapse is perhaps the most critical clinical problem in the use of ECT. In unipolar patients, the current standard is to use continuation monotherapy with a heterocyclic (HCA) or other antidepressant for relapse prevention following ECT. This practice is largely based on three studies conducted in England in the 1960's. Besides methodological flaws, the relevance of this work to present practice is questionable. ECT was frequently a 'first-choice' treatment and standards for adequate pharmacotherapy have changed considerably. Resistance to adequate trials of antidepressants is now the primary indication for ECT and the same class of antidepressant medication that patients failed during the acute episode is commonly used as continuation therapy following ECT. The efficacy of this practice has never been substantiated. In an earlier naturalistic study, we found that the relapse rate was twice as high in patients who had failed one or more adequate preECT HCA trials, compared to patients who came to ECT without any adequate medication trials. Adequacy of postECT pharmacotherapy was only marginally related to relapse. In related research, we have also suggested that medication resistance is a strong predictor of ECT short-term outcome. Using the R10 mechanism, we propose to complete a multi-center study that re-evaluates continuation pharmacotherapy in ECT responders. The study is conducted at the New York State Psychiatric Institute, University of Iowa, and Western Psychiatric Institute and Clinic. A parallel group, random assignment, double-blind design is used to test the relative efficacies of placebo, nortriptyline, and combination nortriptyline-lithium carbonate treatments in preventing relapse following ECT response in primary unipolar patients. It was hypothesized at the outset that nortriptyline alone was of limited benefit for many patients and less effective than its combination with lithium. The interim data document remarkably high relapse rates both with placebo and nortriptyline, and substantial efficacy for the combination treatment. In addition, a larger sample is prospectively evaluated regarding clinical features and treatment history, with standardization of ECT administration across sites. The hypothesis is tested that medication resistance is a potent predictor of ECT efficacy, and, when considered, is responsible for the apparent association of better ECT response in depressed patients with psychosis. This study should have important implications for when ECT is considered during the treatment of the acute depressive episode and, most critically, in establishing an efficacious pharmacological strategy for relapse prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Unknown (R10)
Project #
1R10MH057009-01
Application #
2035644
Study Section
Special Emphasis Panel (ZMH1-CRB-J (02))
Project Start
1997-04-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Feske, Ulrike; Mulsant, Benoit H; Pilkonis, Paul A et al. (2004) Clinical outcome of ECT in patients with major depression and comorbid borderline personality disorder. Am J Psychiatry 161:2073-80
Boylan, L S; Devanand, D P; Lisanby, S H et al. (2001) Focal prefrontal seizures induced by bilateral ECT. J ECT 17:175-9
Sackeim, H A; Haskett, R F; Mulsant, B H et al. (2001) Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA 285:1299-307
Prudic, J; Peyser, S; Sackeim, H A (2000) Subjective memory complaints: a review of patient self-assessment of memory after electroconvulsive therapy. J ECT 16:121-32
Luber, B; Nobler, M S; Moeller, J R et al. (2000) Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. II. Topographic analyses. J ECT 16:229-43
Nobler, M S; Luber, B; Moeller, J R et al. (2000) Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. I. Global analyses. J ECT 16:211-28
Sackeim, H A; Prudic, J; Devanand, D P et al. (2000) A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry 57:425-34
Lisanby, S H; Maddox, J H; Prudic, J et al. (2000) The effects of electroconvulsive therapy on memory of autobiographical and public events. Arch Gen Psychiatry 57:581-90
Boylan, L S; Haskett, R F; Mulsant, B H et al. (2000) Determinants of seizure threshold in ECT: benzodiazepine use, anesthetic dosage, and other factors. J ECT 16:18-Mar
Sackeim, H A; Luber, B; Moeller, J R et al. (2000) Electrophysiological correlates of the adverse cognitive effects of electroconvulsive therapy. J ECT 16:110-20

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