title: Reduction in basal afternoon plasma ACTH during early treatment of depression with fluoxetine.
abstract: BACKGROUND
  Subjects with depression may exhibit activation of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about the response of basal hormone levels to antidepressant therapy.
  
  
  OBJECTIVE
  To determine whether treatment of depression with standard antidepressant medications resulted in reductions in basal activity of afternoon cortisol, ACTH and AVP. A secondary aim was to examine whether there was any difference in hormonal response between an SSRI (fluoxetine) and a tricyclic antidepressant (nortriptyline).
  
  
  METHODS
  Forty-three subjects with a DSM-IV diagnosis of depression (Hamilton score 18.9+/-0.6 at baseline) had five basal venous blood samples drawn at 15-min intervals between 1400 and 1500 hours for cortisol, ACTH and AVP, before and 6 weeks after randomisation to treatment with fluoxetine (n=27) or nortriptyline (n=16).
  
  
  RESULTS
  Both medications resulted in a similar improvement in depression as determined by Hamilton score. In the group as a whole, ACTH levels showed a significant decrease over the 6 weeks (4.1+/-0.4 pmol/l at baseline versus 3.3+/-0.3 at 6 weeks, P<0.05), while cortisol and AVP levels were unchanged. Further analysis revealed that the fall in plasma ACTH occurred predominantly in the subgroup treated with fluoxetine (drug x time interaction by ANOVA, P=0.035). There was a significant relationship between cortisol and ACTH at baseline (r=0.48, P=0.002), that weakened considerably after treatment (r=0.22, P=0.16). The subgroup with baseline hypercortisolemia [mean cortisol >276 nmol/l (10 microg/dl), n=18] demonstrated a reduction in both cortisol and ACTH following treatment, but also showed a loss of the relationship between the two.
  
  
  CONCLUSIONS
  It is postulated that the initial recovery of the HPA axis during the treatment of depression with fluoxetine is mediated via restoration of glucocorticoid negative feedback on ACTH levels.
authors.affiliation: Department of Endocrinology, Christchurch Hospital and Christchurch School of Medicine, New Zealand. warrickinder@bigpond.com
authors.forename: W J
authors.initials: WJ
authors.lastname: Inder
authors.forename: T C
authors.initials: TC
authors.lastname: Prickett
authors.forename: R T
authors.initials: RT
authors.lastname: Mulder
authors.forename: R A
authors.initials: RA
authors.lastname: Donald
authors.forename: P R
authors.initials: PR
authors.lastname: Joyce
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000704:Analysis of Variance; D001127:Arginine Vasopressin / Q000097:blood; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
chemical_list: D000324:Adrenocorticotropic Hormone; D001127:Arginine Vasopressin; D005473:Fluoxetine; D006854:Hydrocortisone; D017367:Selective Serotonin Reuptake Inhibitors