Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial

Research output: Contribution to journalJournal articleResearchpeer-review

Ulla Knorr, Maj Vinberg, Allan Hansen, Marianne Klose, Ulla Feldt-Rasmussen, Linda Hilsted, Jørgen Hasselstrøm, Ulrik Gether, Per Winkel, Christian Gluud, Jørn Wetterslev, Lars Vedel Kessing

Introduction
The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD).

Methods
Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUCtotal) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention.

Results
Change in CorAUCtotal showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUCtotal, rho = -0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUCtotal.

Conclusion
The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age.

Trial Registration
ClinicalTrials.gov [NCT00386841

Original languageEnglish
JournalP L o S One
Volume6
Issue number6
Pages (from-to)e21224
Number of pages10
ISSN1932-6203
DOIs
Publication statusPublished - 2011

ID: 34252835