Loss of antidepressant efficacy during maintenance therapy: possible mechanisms and treatments

UMMS Affiliation

Department of Psychiatry



Document Type


Medical Subject Headings

Adult; Aged; Antidepressive Agents; Antidepressive Agents, Tricyclic; Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Female; Humans; MEDLINE; Male; Middle Aged; Monoamine Oxidase Inhibitors; Placebo Effect; Recurrence; Research Design; Serotonin Uptake Inhibitors; Severity of Illness Index; United States




BACKGROUND: Many patients with unipolar depression experience a return of depressive symptoms while taking a constant maintenance dose of an antidepressant.

METHOD: All cited studies were found using computerized literature searches of the MEDLINE database since 1966.

RESULTS: The return of depressive symptoms during maintenance antidepressant treatment has occurred in 9% to 57% of patients in published trials. Possible explanations include loss of placebo effect, pharmacologic tolerance, increase in disease severity, change in disease pathogenesis, the accumulation of a detrimental metabolite, unrecognized rapid cycling, and prophylactic inefficacy.

CONCLUSION: Although several strategies have been proposed to overcome the loss of antidepressant efficacy, double-blind controlled studies are needed to ascertain the optimal strategy for this perplexing clinical problem.

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Citation: J Clin Psychiatry. 1998 Jun;59(6):279-88.

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