Loss of Antidepressant Efficacy During Maintenance Therapy: Possible Mechanisms and Treatments
J Clin Psychiatry 1998;59:279-288
© Copyright 2014 Physicians Postgraduate Press, Inc.
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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
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.