Project: Research project

Project Details


DESCRIPTION: (Adapted from Applicant's Abstract): Patients treated with
electroconvulsive therapy typically present with the most severe forms of major
depression. Likely due to the increasing representation of medication-resistant
patients, ECT response rates have diminished relative to earlier decades. This
diminished response rate and early relapse following response are critical
clinical problems in the use of ECT. Using the CSMD mechanism, this project
addresses two key issues in the optimization of ECT in patients with major
depression: whether patients treated with ECT should receive concurrent
treatment with antidepressant medications (to enhance ECT outcome and/or
prevent early relapse) and the role of electrode placement (high dosage right
unilateral (RUL) ECT versus low dosage bilateral (BL) ECT) in maximizing
short-term response and minimizing side effects. Patient enrollment, treatment,
and evaluation will be conducted at Wake Forest University, Washington
University, and the Western Psychiatric Institute and Clinic, with staff at the
New York State Psychiatric Institute responsible for study coordination and
monitoring. The study uses a random assignment, double-masked, parallel group
design with two phases. In Phase 1, stratified by the classification of
medication resistance, patients are randomized to concurrent treatment with
nortriptyline (NT, n=210], venlafaxine (VEN, n=210) or placebo (PL, n=210), and
simultaneously to high dosage (6 times threshold) RUL ECT (n=315) or low dosage
(1.5 times threshold) BL ECT (n=315). Based on substantial preliminary data,
the hypotheses will be tested that (1) compared to PL, concurrent NT or VEN
results in superior symptomatic response, without a meaningful difference in
side effects, and (2) RUL and BL ECT are equal in efficacy, but with
significant advantages to high dosage RUL ECT in the magnitude of short- and
long-term cognitive side effects. Support for these hypotheses in a large and
diverse sample should have widespread ramifications for clinical practice. In
the Phase 2 double-masked, 6-month continuation trial, remitters who received
PL during ECT are randomized to NT and lithium (LI) or to VEN-LI. Patients who
had been randomized to concurrent NT or VEN during ECT receive continuation
treatment with NT-LI or VEN-LI, respectively. Standard practice involves the
discontinuation of antidepressant medications prior to ECT, the abrupt
discontinuation of ECT upon response, and then a switch to continuation
pharmacotherapy. This practice likely diminishes response to ECT and heightens
relapse in the first several weeks following ECT. Phase 2 of this study,
centering on the comparison of patients treated with an antidepressant
medication (NT or VEN) or placebo during ECT, will provide the very first data
on whether starting an antidepressant medication from the beginning of the ECT
course reduces the rate of early relapse.
StatusNot started