title: Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression.
abstract: BACKGROUND
  Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention.
  
  
  METHODS
  The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group.
authors: Department of Psychiatry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. ulla.knorr@rh.regionh.dk
authors: Ulla
authors: U
authors: Knorr
authors: Maj
authors: M
authors: Vinberg
authors: Marianne
authors: M
authors: Klose
authors: Ulla
authors: U
authors: Feldt-Rasmussen
authors: Linda
authors: L
authors: Hilsted
authors: Anders
authors: A
authors: Gade
authors: Eva
authors: E
authors: Haastrup
authors: Olaf
authors: O
authors: Paulson
authors: Jørn
authors: J
authors: Wetterslev
authors: Christian
authors: C
authors: Gluud
authors: Ulrik
authors: U
authors: Gether
authors: Lars
authors: L
authors: Kessing
mesh_terms: D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003346:Corticotropin-Releasing Hormone; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D003907:Dexamethasone; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012107:Research Design; D013223:Statistics as Topic
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone