Context Electroconvulsive therapy (ECT) is highly effective for treatment of
major depression, but naturalistic studies show a high rate of relapse after
discontinuation of ECT.
Objective To determine the efficacy of continuation pharmacotherapy with nortriptyline
hydrochloride or combination nortriptyline and lithium carbonate in preventing
post-ECT relapse.
Design Randomized, double-blind, placebo-controlled trial conducted from 1993
to 1998, stratified by medication resistance or presence of psychotic depression
in the index episode.
Setting Two university-based hospitals and 1 private psychiatric hospital.
Patients Of 290 patients with unipolar major depression recruited through clinical
referral who completed an open ECT treatment phase, 159 patients met remitter
criteria; 84 remitting patients were eligible and agreed to participate in
the continuation study.
Interventions Patients were randomly assigned to receive continuation treatment for
24 weeks with placebo (n = 29), nortriptyline (target steady-state level,
75-125 ng/mL) (n = 27), or combination nortriptyline and lithium (target steady-state
level, 0.5-0.9 mEq/L) (n = 28).
Main Outcome Measure Relapse of major depressive episode, compared among the 3 continuation
groups.
Results Nortriptyline-lithium combination therapy had a marked advantage in
time to relapse, superior to both placebo and nortriptyline alone. Over the
24-week trial, the relapse rate for placebo was 84% (95% confidence interval
[CI], 70%-99%); for nortriptyline, 60% (95% CI, 41%-79%); and for nortriptyline-lithium,
39% (95% CI, 19%-59%). All but 1 instance of relapse with nortriptyline-lithium
occurred within 5 weeks of ECT termination, while relapse continued throughout
treatment with placebo or nortriptyline alone. Medication-resistant patients,
female patients, and those with more severe depressive symptoms following
ECT had more rapid relapse.
Conclusions Our study indicates that without active treatment, virtually all remitted
patients relapse within 6 months of stopping ECT. Monotherapy with nortriptyline
has limited efficacy. The combination of nortriptyline and lithium is more
effective, but the relapse rate is still high, particularly during the first
month of continuation therapy.