Loss of Antidepressant Efficacy During Maintenance Therapy: Possible Mechanisms and Treatments

Background: Many patients with unipolardepression experience a return of depressive symptoms whiletaking a constant maintenance dose of an antidepressant.

Method: All cited studies were found usingcomputerized literature searches of the MEDLINE database since1966.

Results: The return of depressive symptomsduring maintenance antidepressant treatment has occurred in 9% to57% of patients in published trials. Possible explanationsinclude loss of placebo effect, pharmacologic tolerance, increasein disease severity, change in disease pathogenesis, theaccumulation of a detrimental metabolite, unrecognized rapidcycling, and prophylactic inefficacy.

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