title: Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial.
abstract: BACKGROUND
  The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD).
  
  
  METHODS
  Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUC(total)) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention.
  
  
  RESULTS
  Change in CorAUC(total) showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUC(total), rho = -0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUC(total).
  
  
  CONCLUSIONS
  The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00386841.
authors: Department of Psychiatry Copenhagen, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. ulla.knorr@regionh.dk
authors: Ulla
authors: U
authors: Knorr
authors: Maj
authors: M
authors: Vinberg
authors: Allan
authors: A
authors: Hansen
authors: Marianne
authors: M
authors: Klose
authors: Ulla
authors: U
authors: Feldt-Rasmussen
authors: Linda
authors: L
authors: Hilsted
authors: Jørgen
authors: J
authors: Hasselstrøm
authors: Ulrik
authors: U
authors: Gether
authors: Per
authors: P
authors: Winkel
authors: Christian
authors: C
authors: Gluud
authors: Jørn
authors: J
authors: Wetterslev
authors: Lars Vedel
authors: LV
authors: Kessing
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005190:Family; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram