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Loss of antidepressant efficacy during maintenance therapy: possible mechanisms and treatments
1Department of Internal Medicine, Cambridge Hospital, Mass, USA.
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.