title: Tachyphylaxis in unipolar major depressive disorder.
abstract: BACKGROUND
  Major depressive disorder is usually a recurring illness, and maintenance treatment is used to forestall or prevent recurrent episodes of depression. This study describes recurrence of major depression despite maintenance pharmacotherapy, termed tachyphylaxis.
  
  
  METHODS
  The study sample consisted of 103 subjects who participated in the NIMH Collaborative Depression Study, a multicenter longitudinal observational study of the mood disorders. Subjects diagnosed with unipolar major depressive disorder according to Research Diagnostic Criteria were enrolled from 1978-1981 and prospectively followed for up to 20 years. As an observational study, treatment was recorded but not controlled by anyone connected with the study. Subjects were selected for the present study if at some point during follow-up they received antidepressant medication for treatment of an episode of major depressive disorder, recovered from this episode, and subsequently received maintenance pharmacotherapy. Some subjects were successfully treated for multiple episodes of major depressive disorder and then received maintenance medication after each of these episodes, resulting in multiple maintenance treatment intervals. Data were collected using the Longitudinal Interval Follow-Up Evaluation, and mixed-effects logistic regression was used to test the association of sociodemographic and clinical variables with tachyphylaxis.
  
  
  RESULTS
  For the 103 subjects, there were 171 maintenance treatment intervals in which a subject received maintenance pharmacotherapy after having recovered from an episode of major depressive disorder. The median duration of maintenance treatment was 20 weeks. Tachyphylaxis occurred during 43 (25%) of these 171 maintenance treatment intervals. The subtype of melancholic (endogenous) major depressive disorder significantly elevated the risk of tachyphylaxis during the subsequent maintenance treatment interval.
  
  
  CONCLUSIONS
  Despite the use of maintenance pharmacotherapy, major depression recurs in a considerable number of patients. Improved prophylaxis for these patients requires other treatment strategies based upon a greater understanding of recurrence.
authors.affiliation: Department of Psychiatry and Human Behavior, Brown University, 593 Eddy Street, Providence, RI 02903, USA. DASolomon@Lifespan.org
authors.forename: David A
authors.initials: DA
authors.lastname: Solomon
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Leon
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Mueller
authors.forename: William
authors.initials: W
authors.lastname: Coryell
authors.forename: Jedediah J
authors.initials: JJ
authors.lastname: Teres
authors.forename: Michael A
authors.initials: MA
authors.lastname: Posternak
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Judd
authors.forename: Jean
authors.initials: J
authors.lastname: Endicott
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy / Q000517:prevention & control; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000517:prevention & control* / Q000523:psychology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D055502:Secondary Prevention; D016019:Survival Analysis; D013618:Tachyphylaxis; D009626:Terminology as Topic; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents