Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine

Martin A Javors, John P. Houston, Janet L. Tekell, Stephen K. Brannan, Alan Frazer

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Drugs thought to be selective inhibitors of either the uptake of serotonin (5-HT) or norepinephrine (NE) are known to be effective antidepressants. In general, a relative selectivity for NE vs. 5-HT uptake inhibition greater than 50-fold in vitro is thought to be sufficient to maintain such selectivity in vivo. To explore this issue, we carried out a study in which depressed patients were treated with either the selective serotonin reuptake inhibitor (SSRI) paroxetine or the selective norepinephrine reuptake inhibitor (SNRI) desipramine. Patients were treated with either drug or placebo for 6 wk. Drug levels in plasma and platelet 5-HT content were measured 12 times during the treatment period using HPLC procedures. Both drug treatments caused a significant reduction of platelet 5-HT content. Paroxetine reduced platelet 5-HT content to approx. 1% of pretreatment levels (n = 3). The inhibition of 5-HT uptake by paroxetine appeared to be immediate and complete. Desipramine reduced platelet 5-HT content to 38.7 ± 6.2 % of pretreatment levels (n = 5) at a mean plasma level of 195 ng/ml. The percent reduction of platelet 5-HT content after 6 wk of drug treatment was proportional to the steady state plasma level of desipramine. The IC50 value of desipramine to reduce platelet 5-HT was 135 ng/ml. These results demonstrate that therapeutic concentrations of the SNRI desipramine as well as the SSRI paroxetine inhibited serotonin uptake in platelets of depressed patients. If such effects occur in the brain, desipramine might have some component of its therapeutic effects due to actions on the uptake of 5-HT.

Original languageEnglish (US)
Pages (from-to)229-235
Number of pages7
JournalInternational Journal of Neuropsychopharmacology
Volume3
Issue number3
DOIs
StatePublished - 2000

Fingerprint

Paroxetine
Desipramine
Serotonin
Blood Platelets
Norepinephrine
Serotonin Uptake Inhibitors
Pharmaceutical Preparations
Therapeutic Uses
Therapeutics
Antidepressive Agents
Inhibitory Concentration 50
High Pressure Liquid Chromatography
Placebos

Keywords

  • Desipramine
  • Paroxetine
  • Platelet
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine. / Javors, Martin A; Houston, John P.; Tekell, Janet L.; Brannan, Stephen K.; Frazer, Alan.

In: International Journal of Neuropsychopharmacology, Vol. 3, No. 3, 2000, p. 229-235.

Research output: Contribution to journalArticle

@article{5f9887f94e4d43bb86765f3f9e2b9aea,
title = "Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine",
abstract = "Drugs thought to be selective inhibitors of either the uptake of serotonin (5-HT) or norepinephrine (NE) are known to be effective antidepressants. In general, a relative selectivity for NE vs. 5-HT uptake inhibition greater than 50-fold in vitro is thought to be sufficient to maintain such selectivity in vivo. To explore this issue, we carried out a study in which depressed patients were treated with either the selective serotonin reuptake inhibitor (SSRI) paroxetine or the selective norepinephrine reuptake inhibitor (SNRI) desipramine. Patients were treated with either drug or placebo for 6 wk. Drug levels in plasma and platelet 5-HT content were measured 12 times during the treatment period using HPLC procedures. Both drug treatments caused a significant reduction of platelet 5-HT content. Paroxetine reduced platelet 5-HT content to approx. 1{\%} of pretreatment levels (n = 3). The inhibition of 5-HT uptake by paroxetine appeared to be immediate and complete. Desipramine reduced platelet 5-HT content to 38.7 ± 6.2 {\%} of pretreatment levels (n = 5) at a mean plasma level of 195 ng/ml. The percent reduction of platelet 5-HT content after 6 wk of drug treatment was proportional to the steady state plasma level of desipramine. The IC50 value of desipramine to reduce platelet 5-HT was 135 ng/ml. These results demonstrate that therapeutic concentrations of the SNRI desipramine as well as the SSRI paroxetine inhibited serotonin uptake in platelets of depressed patients. If such effects occur in the brain, desipramine might have some component of its therapeutic effects due to actions on the uptake of 5-HT.",
keywords = "Desipramine, Paroxetine, Platelet, Serotonin",
author = "Javors, {Martin A} and Houston, {John P.} and Tekell, {Janet L.} and Brannan, {Stephen K.} and Alan Frazer",
year = "2000",
doi = "10.1017/S146114570000198X",
language = "English (US)",
volume = "3",
pages = "229--235",
journal = "The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)",
issn = "1461-1457",
publisher = "Cambridge University Press",
number = "3",

}

TY - JOUR

T1 - Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine

AU - Javors, Martin A

AU - Houston, John P.

AU - Tekell, Janet L.

AU - Brannan, Stephen K.

AU - Frazer, Alan

PY - 2000

Y1 - 2000

N2 - Drugs thought to be selective inhibitors of either the uptake of serotonin (5-HT) or norepinephrine (NE) are known to be effective antidepressants. In general, a relative selectivity for NE vs. 5-HT uptake inhibition greater than 50-fold in vitro is thought to be sufficient to maintain such selectivity in vivo. To explore this issue, we carried out a study in which depressed patients were treated with either the selective serotonin reuptake inhibitor (SSRI) paroxetine or the selective norepinephrine reuptake inhibitor (SNRI) desipramine. Patients were treated with either drug or placebo for 6 wk. Drug levels in plasma and platelet 5-HT content were measured 12 times during the treatment period using HPLC procedures. Both drug treatments caused a significant reduction of platelet 5-HT content. Paroxetine reduced platelet 5-HT content to approx. 1% of pretreatment levels (n = 3). The inhibition of 5-HT uptake by paroxetine appeared to be immediate and complete. Desipramine reduced platelet 5-HT content to 38.7 ± 6.2 % of pretreatment levels (n = 5) at a mean plasma level of 195 ng/ml. The percent reduction of platelet 5-HT content after 6 wk of drug treatment was proportional to the steady state plasma level of desipramine. The IC50 value of desipramine to reduce platelet 5-HT was 135 ng/ml. These results demonstrate that therapeutic concentrations of the SNRI desipramine as well as the SSRI paroxetine inhibited serotonin uptake in platelets of depressed patients. If such effects occur in the brain, desipramine might have some component of its therapeutic effects due to actions on the uptake of 5-HT.

AB - Drugs thought to be selective inhibitors of either the uptake of serotonin (5-HT) or norepinephrine (NE) are known to be effective antidepressants. In general, a relative selectivity for NE vs. 5-HT uptake inhibition greater than 50-fold in vitro is thought to be sufficient to maintain such selectivity in vivo. To explore this issue, we carried out a study in which depressed patients were treated with either the selective serotonin reuptake inhibitor (SSRI) paroxetine or the selective norepinephrine reuptake inhibitor (SNRI) desipramine. Patients were treated with either drug or placebo for 6 wk. Drug levels in plasma and platelet 5-HT content were measured 12 times during the treatment period using HPLC procedures. Both drug treatments caused a significant reduction of platelet 5-HT content. Paroxetine reduced platelet 5-HT content to approx. 1% of pretreatment levels (n = 3). The inhibition of 5-HT uptake by paroxetine appeared to be immediate and complete. Desipramine reduced platelet 5-HT content to 38.7 ± 6.2 % of pretreatment levels (n = 5) at a mean plasma level of 195 ng/ml. The percent reduction of platelet 5-HT content after 6 wk of drug treatment was proportional to the steady state plasma level of desipramine. The IC50 value of desipramine to reduce platelet 5-HT was 135 ng/ml. These results demonstrate that therapeutic concentrations of the SNRI desipramine as well as the SSRI paroxetine inhibited serotonin uptake in platelets of depressed patients. If such effects occur in the brain, desipramine might have some component of its therapeutic effects due to actions on the uptake of 5-HT.

KW - Desipramine

KW - Paroxetine

KW - Platelet

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=0033803685&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033803685&partnerID=8YFLogxK

U2 - 10.1017/S146114570000198X

DO - 10.1017/S146114570000198X

M3 - Article

VL - 3

SP - 229

EP - 235

JO - The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)

JF - The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)

SN - 1461-1457

IS - 3

ER -