Electroconvulsive therapy (ECT) is an extremely effective treatment for major depression and patients that receive this modality frequently present with the most severe, recurrent forms of this illness. Perhaps the most critical clinical issue facing the field of ECT is the problem of early relapse. In unipolar patients who have responded to ECT, the current standard of practice is to use tricyclic antidepressant (TCA) continuation therapy in the prevention of relapse. This practice is based largely on the findings of three controlled trials that were conducted in England in the 1960's. Besides serious methodological flaws, the relevance of these studies to present practice is questionable. In this early work, ECT was frequently used as a 'first choice' treatment and standards for adequate pharmacological treatment have changed considerably over this period. In current practice, resistance to adequate trials of antidepressant medications is a primary indication for ECT and medication-resistant patients form a large proportion of ECT samples. Consequently, it is common to use as continuation therapy following ECT the very same class of antidepressant medications that patients failed during treatment of the acute episode. The efficacy of this practice has never been substantiated. Indeed, in a preliminary prospective, naturalistic study, we found that the relapse rate was twice as high in patients who had failed one or more adequate TCA trials prior to ECT, compared to patients who came to ECT without receiving an adequate medication trial. Adequacy of postECT TCA pharmacotherapy was only marginally related to relapse rates, with the patients who benefitted appearing to be only those who had not failed adequate antidepressant treatment prior to ECT. In related research, we have also found that medication resistance appears to be a strong predictor of ECT outcome. Patients who failed adequate TCA trials prior to ECT had a lower ECT response rate. Here we propose to re-evaluate the utility of continuation pharmacotherapy in ECT responders. In a multi-center trial, involving the Carrier Foundation, New York State Psychiatric Institute, and Western Psychiatric Institute and Clinic, a parallel group, random assignment, double-blind design will be used to establish the relative efficacies of placebo, nortriptyline, and combination nortriptyline-lithium carbonate continuation therapies in the prevention of relapse in unipolar patients following response to ECT. It is hypothesized that nortriptyline alone or its combination with lithium will be effective in patients without documented medication resistance, but that only the combination continuation treatment will be efficacious in patients who have failed one or more trials of a cyclic antidepressant prior to ECT. In addition, a larger sample of patients will be prospectively evaluated with respect to clinical features and treatment history, with standardization of ECT administration across sites. The hypothesis will be tested that medication resistance is also a potent predictor of ECT efficacy, and, when considered, is responsible for the apparent association of better ECT response in depressed patients with psychosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH047739-03
Application #
2247798
Study Section
Special Emphasis Panel (SRCM)
Project Start
1992-05-01
Project End
1997-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
3
Fiscal Year
1994
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
Brakemeier, Eva-Lotta; Berman, Robert; Prudic, Joan et al. (2011) Self-evaluation of the cognitive effects of electroconvulsive therapy. J ECT 27:59-66
Sackeim, Harold A; Prudic, Joan; Nobler, Mitchell S et al. (2008) Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. Brain Stimul 1:71-83
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
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
Sobin, C; Sackeim, H A (1997) Psychomotor symptoms of depression. Am J Psychiatry 154:4-17
Sackeim, H A; Luber, B; Katzman, G P et al. (1996) The effects of electroconvulsive therapy on quantitative electroencephalograms. Relationship to clinical outcome. Arch Gen Psychiatry 53:814-24
Lisanby, S H; Devanand, D P; Nobler, M S et al. (1996) Exceptionally high seizure threshold: ECT device limitations. Convuls Ther 12:156-64
Coleman, E A; Sackeim, H A; Prudic, J et al. (1996) Subjective memory complaints prior to and following electroconvulsive therapy. Biol Psychiatry 39:346-56
Devanand, D P; Fitzsimons, L; Prudic, J et al. (1995) Subjective side effects during electroconvulsive therapy. Convuls Ther 11:232-40
Devanand, D P (1995) Does electroconvulsive therapy damage brain cells? Semin Neurol 15:351-7

Showing the most recent 10 out of 23 publications