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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

Authors :
Aleksander A. Mathé
Pierre Baumann
Georg Nikisch
Jürgen Bohner
Adelheid Czernik
Hans Ågren
Chin B. Eap
Jutta Thiele
Source :
Psychopharmacology. 181:751-760
Publication Year :
2005
Publisher :
Springer Science and Business Media LLC, 2005.

Abstract

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. 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). 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. 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

Details

ISSN :
14322072 and 00333158
Volume :
181
Database :
OpenAIRE
Journal :
Psychopharmacology
Accession number :
edsair.doi.dedup.....d8bc308237ce040156fb348398a721e9