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Different responses to dexamethasone and prednisolone in the same depressed patients

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Abstract

Rationale

Patients with major depression show hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, but the mechanisms underlying this abnormality are still unclear.

Objectives

We have compared two synthetic glucorticoids, dexamethasone and prednisolone, in their ability to suppress the hypothalamic–pituitary–adrenal (HPA) axis in depressed patients. Dexamethasone probes glucocorticoid receptor (GR) function, while prednisolone probes both GR and mineralocorticoid receptor (MR) function.

Materials and methods

We used a single-blind, repeated-measure design. We administered placebo, prednisolone (5 mg) or dexamethasone (0.5 mg), at 22:00, to 18 severe, treatment-resistant depressed inpatients (15 of them with a history of childhood trauma) and 14 healthy volunteers. On the following days, we collected salivary cortisol from 9:00 to 22:00.

Results

Depressed patients had higher salivary cortisol levels compared with controls, at baseline and after both prednisolone and dexamethasone (p<0.001). Consistent with previous studies, depressed inpatients showed impaired suppression by dexamethasone: based on the analysis of the areas under the curve (AUCs), suppression by dexamethasone (0.5 mg) was −85% in controls vs −46% in depressed patients (p=0.018). However, the same depressed patients showed normal suppression by prednisolone (5 mg): suppression was −41% in controls and −36% in depressed patients (p=0.6).

Conclusions

We suggest that the additional effects of prednisolone on the MR explain the different responses to these glucocorticoids in the same depressed patients.

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Acknowledgements

This research has been supported by a 2003 and a 2005 Young Investigator Awards from the National Alliance for Research on Schizophrenia and Depression (NARSAD), and by a Clinician Scientist Fellowship (2004) from the UK Medical Research Council (MRC), to C.M. Pariante. Dr. Pariante’s research is also funded by the Guy’s & St Thomas’ Charitable Foundation. Dr. M. Juruena is supported by a CAPES Fellowship Award and by a 2006 Young Investigator Awards from the NARSAD. The authors are particularly grateful to Dr. Jeffrey Fry (School of Biomedical Sciences, Nottingham, UK) and David Czock (Division of Nephrology, University Hospital Ulm, Ulm, Germany) for their contribution to the analysis and interpretation of pharmacokinetic data.

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Authors and Affiliations

  1. Stress, Psychiatry and Immunology Laboratory (SPI-Lab), Section of Clinical Neuropharmacology, Institute of Psychiatry, King’s College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK

    Mario F. Juruena & Carmine M. Pariante

  2. Section of Neurobiology of Mood Disorders, Institute of Psychiatry, King’s College London, London, UK

    Mario F. Juruena & Anthony J. Cleare

  3. Affective Disorders Unit Laboratory, Bethlem Royal Hospital, Beckenham, Kent, UK

    Mario F. Juruena, Anthony J. Cleare, Andrew S. Papadopoulos & Lucia Poon

  4. Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK

    Stafford Lightman

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  1. Mario F. Juruena
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  2. Anthony J. Cleare
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  3. Andrew S. Papadopoulos
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  4. Lucia Poon
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  5. Stafford Lightman
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  6. Carmine M. Pariante
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Correspondence to Carmine M. Pariante.

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Juruena, M.F., Cleare, A.J., Papadopoulos, A.S. et al. Different responses to dexamethasone and prednisolone in the same depressed patients. Psychopharmacology 189, 225–235 (2006). https://doi.org/10.1007/s00213-006-0555-4

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  • DOI: https://doi.org/10.1007/s00213-006-0555-4

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