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Neuroendocrine response to intravenous citalopram in healthy control subjects: pharmacokinetic influences

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Abstract

Rationale

The neuroendocrine response to intravenous citalopram may provide an acute, functional, in vivo measure of the neural serotonin (5-HT) system.

Objective

To refine the quantification of acute neuroendocrine responses following intravenous citalopram in studies of 5-HT function.

Methods

In 75 adult healthy subjects taking part in four similar protocols, we measured plasma prolactin and cortisol, as well as serial citalopram concentrations following intravenous citalopram (10 mg, 20 mg, 40 mg, 0.33 mg/kg) and placebo. The relationship between the AUC for intravenous citalopram during the first 150 min (AUC150) and the magnitude of the neuroendocrine response was determined. The role of pharmacokinetic (PK) parameters, as well as sensitivity to placebo injections, in influencing the neuroendocrine response to citalopram was then evaluated.

Results

Citalopram produced a dose-dependent increase in cortisol and prolactin. The maximal increase from baseline correlated significantly but modestly with citalopram’s AUC150 (prolactin r2=0.23, P<0.0001; cortisol r2=0.3, P<0.0001). Additionally, citalopram’s AUC150 was affected by between-subject differences in both the peripheral and central volume of distribution. However, the neuroendocrine responses to citalopram did not correlate with the responses to placebo.

Conclusions

The parenteral citalopram challenge test is characterized by a modest concentration-response relationship, with concentration influenced by variable PK factors. Accounting for individual differences in drug distribution may improve the power of the citalopram challenge test, when used as an in vivo measure of central 5-HT function.

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Acknowledgements

This research was supported by NIMH grants MH65416, MH64173, MH30915, MH52247, RR00056, MH16804, HL40962, MH 49936, MH57078, MH01621, and MH46823 and NIBIBP41 EB-001975. The authors thank Margaret Kirshner for technical assistance.

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Authors and Affiliations

  1. Department of Psychiatry, Western Psychiatric Institute and Clinic, Pittsburgh, USA

    Francis E. Lotrich, Robert Bies & Bruce G. Pollock

  2. Department of Pharmaceutical Sciences, University of Pittsburgh Medical Center, Pittsburgh, USA

    Robert Bies & Bruce G. Pollock

  3. Department of Pharmacology, University of Pittsburgh Medical Center, Pittsburgh, USA

    Bruce G. Pollock

  4. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, USA

    Matthew F. Muldoon

  5. Department of Psychology, University of Pittsburgh, Pittsburgh, USA

    Stephen B. Manuck

  6. New York Department of Psychiatry Research, Zucker Hillside Hospital and Center for Neurosciences, North Shore-Long Island Jewish Research Institute and Health System, New York, USA

    Gwenn S. Smith

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  1. Francis E. Lotrich
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  2. Robert Bies
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  3. Matthew F. Muldoon
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  4. Stephen B. Manuck
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  5. Gwenn S. Smith
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  6. Bruce G. Pollock
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Correspondence to Francis E. Lotrich.

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Lotrich, F.E., Bies, R., Muldoon, M.F. et al. Neuroendocrine response to intravenous citalopram in healthy control subjects: pharmacokinetic influences. Psychopharmacology 178, 268–275 (2005). https://doi.org/10.1007/s00213-004-2006-4

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  • DOI: https://doi.org/10.1007/s00213-004-2006-4

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