This R01 is a competitive renewal of a MERIT Award. When this project started (1981), the universal view was that the efficacy of ECT was dependent on the generalized seizure, while its cognitive effects were largely determined by electrical dosage. Nonetheless, standard practice involved treating all patients with the same electrical dose, typically at device maximum. Across three studies, we demonstrated marked individual differences in seizure threshold (ST). Many patients were treated orders of magnitude above ST, accounting for much of the adverse cognitive effects of ECT. We also demonstrated that the efficacy of right unilateral (RUL)ECT is highly dependent on the degree to which dosage exceeds ST. These findings have been widely replicated. In our most recent study (started and completed during the MERIT Award period), high dosage RUL ECT equaled the efficacy of a robust form of bilateral (BL) ECT, and had clinically significant advantages in acute, short-term, and long-term cognitive side effects. These findings have already had impact on practice, and should help resolve the > 40 year controversy regarding the relative merits of RUL and BL ECT. The proposed study (Study 4) began during the MERIT Award period, and this application requests support for its completion. In addition to replicating the key findings regarding the relative merits of high dosage RUL compared to BL ECT, this study takes a new direction. The traditional ECT stimulus configuration is nonphysiologic. The standard pulse width (PW) used in ECT (1-2 ms) greatly exceeds the chronaxie for the optimal stimulation necessary for neuronal depoladzation and seizure production (eg, 0.04-0.2 ms). Excessive PW results in stimulation during refractory periods long following neuronal discharge. By reducing the PW of the ECT stimulus, we should maintain efficacy, but substantially reduce cognitive side effects. Our preliminary data suggest that the magnitude of this effect equals or exceeds the difference in cognitive effects between RUL and BL ECT, and, in fact, the extraordinary difference between sine wave and brief pulse stimulation. This new study uses a randomized, double-masked, parallel group, fully factorial [RUL vs. BL ECT and ultrabrief PW (0 ms) vs. traditional PW (1.5 ms)] design, with both RUL conditions treated at 6 times initial ST and both BL conditions treated at 2.5 times initial ST. We hypothesize that high dose RUL ECT has significant advantages over moderate dose BL ECT [with both at traditional PW]. Most critically, use of an ultrabrief PW is equally effective as a long PW, but markedly reduces the short- and long-term cognitive burden of ECT, and is also superior in effects on functional status, subjective cognitive outcome, and neurophysiological alterations. Such findings should have fundamental impact on our understanding of mechanisms and on the practice of ECT.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH035636-22
Application #
6647038
Study Section
Special Emphasis Panel (ZMH1-ITV-D (01))
Program Officer
Rudorfer, Matthew V
Project Start
1988-08-01
Project End
2004-11-30
Budget Start
2003-08-01
Budget End
2004-11-30
Support Year
22
Fiscal Year
2003
Total Cost
$393,994
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Sackeim, Harold A (2014) Autobiographical memory and electroconvulsive therapy: do not throw out the baby. J ECT 30:177-86
Prudic, Joan; Haskett, Roger F; McCall, W Vaughn et al. (2013) Pharmacological strategies in the prevention of relapse after electroconvulsive therapy. J ECT 29:3-12
McCall, W Vaughn; Reboussin, David; Prudic, Joan et al. (2013) Poor health-related quality of life prior to ECT in depressed patients normalizes with sustained remission after ECT. J Affect Disord 147:107-11
Devanand, Devangere; Lee, Joseph; Luchsinger, Jose et al. (2013) Lessons from epidemiologic research about risk factors, modifiers, and progression of late onset Alzheimer's Disease in New York City at Columbia University Medical Center. J Alzheimers Dis 33 Suppl 1:S447-55
McCall, W Vaughn; Rosenquist, Peter B; Kimball, James et al. (2011) Health-related quality of life in a clinical trial of ECT followed by continuation pharmacotherapy: effects immediately after ECT and at 24 weeks. J ECT 27:97-102
Brakemeier, Eva-Lotta; Berman, Robert; Prudic, Joan et al. (2011) Self-evaluation of the cognitive effects of electroconvulsive therapy. J ECT 27:59-66
Devanand, D P; Van Heertum, Ronald L; Kegeles, Lawrence S et al. (2010) (99m)Tc hexamethyl-propylene-aminoxime single-photon emission computed tomography prediction of conversion from mild cognitive impairment to Alzheimer disease. Am J Geriatr Psychiatry 18:959-72
Sackeim, Harold A; Dillingham, Elaine M; Prudic, Joan et al. (2009) Effect of concomitant pharmacotherapy on electroconvulsive therapy outcomes: short-term efficacy and adverse effects. Arch Gen Psychiatry 66:729-37
Devanand, Davangere P; Liu, Xinhua; Tabert, Matthias H et al. (2008) Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease. Biol Psychiatry 64:871-9
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

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