Loss of antidepressant efficacy during maintenance therapy: possible mechanisms and treatments.
BACKGROUND
Many patients with unipolar depression experience a return of depressive symptoms while taking a constant maintenance dose of an antidepressant.


METHODS
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.


CONCLUSIONS
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.
Department of Internal Medicine, Cambridge Hospital, Mass, USA.
S E
SE
Byrne
A J
AJ
Rothschild
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy / Q000517:prevention & control* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D016239:MEDLINE; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D015990:Placebo Effect; D012107:Research Design; D055502:Secondary Prevention; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D012720:Severity of Illness Index; D014481:United States
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D008996:Monoamine Oxidase Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors