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A placebo-controlled study of sertraline’s effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults

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Abstract

Rationale

The dexamethasone/corticotropin-releasing hormone (Dex/CRH) test is a neuroendocrine probe involving serial blood sampling of cortisol during a standardized pharmacological challenge without inducing psychological distress in humans. Some past studies in depressed patients have shown a “normalization” or decrease in cortisol response to the Dex/CRH test following successful treatment with an antidepressant. Studies in nondepressed healthy adult samples have also shown aberrant cortisol reactivity to be associated with depression risk factors. These findings prompted research into the use of the Dex/CRH test as a tool for developing antidepressant drugs.

Objectives

In this study, the Dex/CRH test was evaluated with regard to its potential utility for drug development in nonclinical samples.

Methods

The Dex/CRH test was administered before and after 6 weeks of blinded treatment with either sertraline 100 mg/day or matching placebo in 22 healthy adults (13 women, nine men).

Results

Cortisol response to the Dex/CRH test increased following treatment with standard doses of sertraline, compared to placebo, after controlling for age and sex.

Conclusions

The observed pattern of change contrasts with results from published studies in depressed patients and with our initial hypothesis.

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Acknowledgments

The authors thank Kelly Colombo, B.A. for her assistance with data management, Ashley Clement for her research assistant support in manuscript preparation, and Daniel Gonzalez for performance of the cortisol assays. This work was supported by an investigator-initiated grant from Pfizer Inc. (LLC) and by the Department of Veterans Affairs (CWW).

Conflicts of interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Mood Disorders Research Program and Laboratory for Clinical Neuroscience, Brown Department of Psychiatry and Human Behavior, Butler Hospital, 345 Blackstone Blvd., Providence, RI, 02906, USA

    Linda L. Carpenter, Audrey R. Tyrka, Janet K. Lee, Aaron P. Tracy & Lawrence H. Price

  2. Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA, 98108, USA

    Charles W. Wilkinson

  3. Department of Psychiatry and Behavioral Sciences, University of Washington, 1660 S. Columbian Way, Seattle, WA, 98108, USA

    Charles W. Wilkinson

Authors
  1. Linda L. Carpenter
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  2. Audrey R. Tyrka
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  3. Janet K. Lee
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  4. Aaron P. Tracy
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  5. Charles W. Wilkinson
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  6. Lawrence H. Price
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Correspondence to Linda L. Carpenter.

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Carpenter, L.L., Tyrka, A.R., Lee, J.K. et al. A placebo-controlled study of sertraline’s effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults. Psychopharmacology 218, 371–379 (2011). https://doi.org/10.1007/s00213-011-2336-y

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