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Original Contribution
March 14, 2001

Continuation Pharmacotherapy in the Prevention of Relapse Following Electroconvulsive Therapy: A Randomized Controlled Trial

Author Affiliations

Author Affiliations: Departments of Biological Psychiatry (Drs Sackeim and Prudic), Neuroscience (Dr Mann), and Analytical Psychopharmacology (Mr Cooper), New York State Psychiatric Institute, and the Departments of Psychiatry (Drs Sackeim, Mann, and Prudic and Mr Cooper) and Radiology (Drs Sackeim and Mann), College of Physicians and Surgeons, Columbia University, New York, NY; Western Psychiatric Institute and Clinic and the Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pa (Drs Haskett, Mulsant, and Thase); Carrier Foundation, Belle Meade, NJ (Drs Pettinati and Greenberg); Department of Psychiatry, University of Iowa, Iowa City (Dr Crowe). Dr Pettinati is now with the Department of Psychiatry, University of Pennsylvania, Philadelphia; Dr Greenberg, the Department of Psychiatry, St Francis Hospital, Jersey City, NJ.

JAMA. 2001;285(10):1299-1307. doi:10.1001/jama.285.10.1299

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.