Byrne, Sarah E.Rothschild, Anthony J.2022-08-232022-08-231998-07-222010-05-05J Clin Psychiatry. 1998 Jun;59(6):279-88.0160-6689 (Linking)9671339https://hdl.handle.net/20.500.14038/45954BACKGROUND: 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.en-USAdultAgedAntidepressive AgentsAntidepressive Agents, TricyclicClinical Trials as TopicDepressive DisorderDose-Response Relationship, DrugDrug Administration ScheduleDrug Therapy, CombinationDrug ToleranceFemaleHumansMEDLINEMaleMiddle AgedMonoamine Oxidase InhibitorsPlacebo EffectRecurrenceResearch DesignSerotonin Uptake InhibitorsSeverity of Illness IndexUnited StatesPsychiatryJournal Articlehttps://escholarship.umassmed.edu/psych_pp/481299395psych_pp/48