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Cited by 686Electroconvulsive Therapy StudiesTreatment of Major DepressionBipolar Disorder and Treatment

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

Sackeim, Harold A., Haskett, Roger F., Mulsant, Benoit H., Thase, Michael E., Mann, J. John, Pettinati, Helen M., Greenberg, Robert M., Crowe, Raymond R. +2 more·2001·JAMA
DOI 10.1001/jama.285.10.1299
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Abstract

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.

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Authors
Sackeim, H. A., Haskett, R. F., Mulsant, B. H., Thase, M. E., Mann, J. J., Pettinati, H. M., Greenberg, R. M., Crowe, R. R., Cooper, T. B., & Prudic, J.
Affiliations
  • American Medical Association (US)
  • Columbia University (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2001-03-14
Volume
285
Issue
10
Pages
1299
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.285.10.1299
OpenAlex
W2071696563
Cited by
686
References
69
Citations by year
2026: 17 · 2025: 17 · 2024: 18 · 2023: 17 · 2022: 32 · 2021: 27 · 2020: 34 · 2019: 39 · 2018: 25 · 2017: 19 · 2016: 27 · 2015: 23 · 2014: 17 · 2013: 39 · 2012: 30
FWCI
22.41
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • DigitalGeorgetown (Georgetown University Library) (submittedVersion)
Funders
  • National Institutes of Health (5r01mh047739-02, 5r10mh057009-03, 5r01mh047709-02)
  • National Institute of Mental Health (R01-MH-30915, R01 MH49786, R37MH035636, R37 MH35636, R01 MH48512, R01 MH47709, R10 MH57804, R01 MH47739, R01 MH 01613, R10 MH57009, R01 MH-52247)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords
electroconvulsive therapy, major depressive disorder, relapse prevention, nortriptyline, lithium carbonate, antidepressant maintenance, remission
MeSH terms
Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Drug Therapy, Combination, Electroconvulsive Therapy, Female, Humans, Male, Middle Aged, Nortriptyline, Recurrence, Regression Analysis, Survival Analysis, Lithium Carbonate

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