The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate

Michael A. Derby, Lu Zhang, Jill C. Chappell, Celedon R. Gonzales, John Callaghan, Mark Leibowitz, Larry Ereshefsky, David Hoelscher, Philip T. Leese, Malcolm I. Mitchell

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The effects of supratherapeutic dosages of duloxetine, a serotonin and norepinephrine reuptake inhibitor, on blood pressure and pulse rate were assessed in a multicenter, double-blind, randomized, placebo-controlled, crossover study in 117 healthy women aged 19 to 74 years. Dosages were escalated from 60 mg twice daily (BID) to 200 mg BID over 16 days. Vital signs were monitored at baseline, before morning dosing, and sequentially at steady state. Duloxetine produced increases in supine systolic and diastolic blood pressures, which reached maximums of ∼12 mm Hg and ∼7 mm Hg above baseline, respectively, during dosing at 120 mg BID and then stabilized. Supine pulse rate increased gradually with dose, reaching 10 to 12 bpm above baseline after 4 days of dosing at 200 mg BID. Duloxetine caused changes in orthostatic blood pressures and pulse rate that reached plateau values after 3 to 4 days of dosing at 160 mg BID and were generally not associated with subjectively reported orthostatic-related adverse events. All vital signs normalized by 1 to 2 days after study drug discontinuation. Prehypertensive subjects may become hypertensive upon initial duloxetine dosing, but this can be predicted from predose blood pressure. Short-term supratherapeutic duloxetine dosages up to 200 mg BID are not well tolerated but are generally not associated with severe, clinically important adverse events. Overall, the types of adverse events reported in this study were similar to those in other studies of duloxetine in healthy subjects.

Original languageEnglish
Pages (from-to)384-393
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume49
Issue number6
DOIs
StatePublished - Jun 2007

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Heart Rate
Blood Pressure
Vital Signs
Cross-Over Studies
Duloxetine Hydrochloride
Healthy Volunteers
Placebos
Pharmaceutical Preparations

Keywords

  • Blood pressure
  • Duloxetine
  • Orthostasis
  • Supratherapeutic dose
  • Vital signs

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Derby, M. A., Zhang, L., Chappell, J. C., Gonzales, C. R., Callaghan, J., Leibowitz, M., ... Mitchell, M. I. (2007). The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate. Journal of Cardiovascular Pharmacology, 49(6), 384-393. https://doi.org/10.1097/FJC.0b013e31804d1cce

The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate. / Derby, Michael A.; Zhang, Lu; Chappell, Jill C.; Gonzales, Celedon R.; Callaghan, John; Leibowitz, Mark; Ereshefsky, Larry; Hoelscher, David; Leese, Philip T.; Mitchell, Malcolm I.

In: Journal of Cardiovascular Pharmacology, Vol. 49, No. 6, 06.2007, p. 384-393.

Research output: Contribution to journalArticle

Derby, MA, Zhang, L, Chappell, JC, Gonzales, CR, Callaghan, J, Leibowitz, M, Ereshefsky, L, Hoelscher, D, Leese, PT & Mitchell, MI 2007, 'The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate', Journal of Cardiovascular Pharmacology, vol. 49, no. 6, pp. 384-393. https://doi.org/10.1097/FJC.0b013e31804d1cce
Derby, Michael A. ; Zhang, Lu ; Chappell, Jill C. ; Gonzales, Celedon R. ; Callaghan, John ; Leibowitz, Mark ; Ereshefsky, Larry ; Hoelscher, David ; Leese, Philip T. ; Mitchell, Malcolm I. / The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate. In: Journal of Cardiovascular Pharmacology. 2007 ; Vol. 49, No. 6. pp. 384-393.
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