Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial
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Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial. / Knorr, Ulla; Vinberg, Maj; Hansen, Allan; Klose, Marianne; Feldt-Rasmussen, Ulla; Hilsted, Linda; Hasselstrøm, Jørgen; Gether, Ulrik; Winkel, Per; Gluud, Christian; Wetterslev, Jørn; Kessing, Lars Vedel.
In: P L o S One, Vol. 6, No. 6, 2011, p. e21224.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial
AU - Knorr, Ulla
AU - Vinberg, Maj
AU - Hansen, Allan
AU - Klose, Marianne
AU - Feldt-Rasmussen, Ulla
AU - Hilsted, Linda
AU - Hasselstrøm, Jørgen
AU - Gether, Ulrik
AU - Winkel, Per
AU - Gluud, Christian
AU - Wetterslev, Jørn
AU - Kessing, Lars Vedel
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
U2 - 10.1371/journal.pone.0021224
DO - 10.1371/journal.pone.0021224
M3 - Journal article
C2 - 21738622
VL - 6
SP - e21224
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 6
ER -
ID: 34252835