Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

Details

Serval ID
serval:BIB_01B5984DAAF6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.
Journal
Psychopharmacology
Author(s)
Nikisch G., Mathé A.A., Czernik A., Thiele J., Bohner J., Eap C.B., Agren H., Baumann P.
ISSN
0033-3158
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
181
Number
4
Pages
751-60
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.
Keywords
Adrenocorticotropic Hormone, Adult, Blood-Brain Barrier, Citalopram, Corticotropin-Releasing Hormone, Depressive Disorder, Major, Dexamethasone, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Long-Term Care, Male, Middle Aged, Pituitary-Adrenal System, Prognosis, Retreatment, Treatment Failure
Pubmed
Web of science
Create date
10/03/2008 10:53
Last modification date
20/08/2019 12:23
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