title: HPA axis activation in major depression and response to fluoxetine: a pilot study.
abstract: Hypothalamic-pituitary-adrenal (HPA) axis activation is a frequently observed phenomenon in major depression. However, whether this activation has any implications for treatment is unknown. To address this question, we examined baseline response to metyrapone and 6-week response to fluoxetine. Premenopausal women (n = 20) who met criteria for major depression with no other confounding Axis I disorders, medications, or medical illnesses and were not taking hormonal contraceptives were evaluated with an evening metyrapone challenge before the onset of treatment. Twenty-one normal women were also studied with the evening metyrapone challenge. The depressed patients then entered an open label treatment with fluoxetine for 6 weeks. Subjects were classified as responders if they demonstrated a 50% or greater decrease in Hamilton Depression Rating Scale rating. As a group, the depressed women demonstrated significantly increased ACTH secretion compared to control women before the onset of treatment, during the metyrapone challenge. Before treatment, women who were non-responders to fluoxetine showed increased HPA axis activation compared to controls, while the fluoxetine responders did not differ significantly from normal subjects in their ACTH levels during metyrapone challenge. These results suggest that overactivity of the HPA axis may be one factor associated with slower response to fluoxetine. This may reflect the greater severity of subjects with HPA axis dysregulation or the need to normalize the HPA axis with medications for optimal response.
authors.affiliation: Department of Psychiatry, The Mental Health Research Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI 48109-0729, USA. eayoung@umich.edu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Young
authors.forename: Margaret
authors.initials: M
authors.lastname: Altemus
authors.forename: Juan F
authors.initials: JF
authors.lastname: Lopez
authors.forename: James H
authors.initials: JH
authors.lastname: Kocsis
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
authors.forename: Charles
authors.initials: C
authors.lastname: DeBattista
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D002940:Circadian Rhythm; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D008797:Metyrapone; D008875:Middle Aged; D010865:Pilot Projects; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D013268:Stimulation, Chemical; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D000324:Adrenocorticotropic Hormone; D008797:Metyrapone