Research article summary (published 29 Sep 2002):

Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine.

Full Abstract

OBJECTIVE: The study examined whether paroxetine inhibits the human norepinephrine transporter in addition to the human serotonin (5-HT) transporter in patients with major depressive disorder. METHOD: In an open-label, parallel-group, forced-titration study, 52 outpatients with DSM-IV major depressive disorder and a baseline Montgomery Asberg Depression Rating Scale score > or =20 were randomly assigned to treatment with paroxetine (to 60 mg/day) or desipramine (to 30 mg/day) in a 3-to-1 ratio, respectively. Norepinephrine and 5-HT transporter function were assayed by using human transporter transfected cells in the presence of serum collected at baseline and the end of each treatment week. Data from 36 patients were analyzed. RESULTS: Paroxetine decreased norepinephrine uptake to 73% of control (27% inhibition) at an average serum concentration of 100 ng/ml and 57% of control (43% inhibition) at 200 ng/ml. Uptake of 5-HT was decreased to less than 15% (greater than 85% inhibition) of control at these paroxetine concentrations. Desipramine decreased norepinephrine uptake to near maximal 15% of control (85% inhibition) at 100 ng/ml. Uptake of 5-HT was decreased to 82% of control (18% inhibition) at 100 ng/ml and 49% of control (51% inhibition) at 500 ng/ml. CONCLUSIONS: Paroxetine, currently classified as a selective 5-HT reuptake inhibitor, can act as a 5-HT/norepinephrine uptake inhibitor in vivo. The clinical significance of this action on norepinephrine uptake is currently unknown, but this action may contribute to the broad therapeutic efficacy of paroxetine in the treatment of depression, panic disorder, social anxiety disorder, posttraumatic stress disorder, and generalized anxiety disorder.

Author information

Author/s: Gilmor, Michelle L (ML); Owens, Michael J (MJ); Nemeroff, Charles B (CB);

Affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000, WMB Building, Atlanta, GA 30322, USA.

Journal and publication information

Publication Type: Clinical Trial; Comparative Study; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Journal: The American journal of psychiatry (Am J Psychiatry), published in United States. (Language: eng)

Reference: 2002-Oct; vol 159 (issue 10) : pp 1702-10

Dates: Created 2002/10/02; Completed 2002/10/23; Revised 2006/11/15;

PMID: 12359676, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Ambulatory Care Carrier Proteins - antagonists & inhibitors; blood Depressive Disorder - drug therapy; metabolism Desipramine - blood; pharmacology; therapeutic use Dose-Response Relationship, Drug Female Humans Male Membrane Glycoproteins - antagonists & inhibitors; blood Membrane Transport Proteins Middle Aged

Middle Aged Nerve Tissue Proteins Neurotransmitter Uptake Inhibitors - pharmacology; therapeutic use Norepinephrine - antagonists & inhibitors; blood; metabolism Norepinephrine Plasma Membrane Transport Proteins Paroxetine - blood; pharmacology; therapeutic use Psychiatric Status Rating Scales Serotonin - blood; metabolism Serotonin Plasma Membrane Transport Proteins Serotonin Uptake Inhibitors - pharmacology; therapeutic use Symporters - antagonists & inhibitors; blood Treatment Outcome

Associated Chemicals: Carrier Proteins (0) ; Membrane Glycoproteins (0) ; Membrane Transport Proteins (0) ; Nerve Tissue Proteins (0) ; Neurotransmitter Uptake Inhibitors (0) ; Norepinephrine Plasma Membrane Transport Proteins (0) ; SLC6A2 protein, human (0) ; SLC6A4 protein, human (0) ; Serotonin Plasma Membrane Transport Proteins (0) ; Serotonin Uptake Inhibitors (0) ; Symporters (0) ; Desipramine (50-47-5) ; Serotonin (50-67-9) ; Norepinephrine (51-41-2) ; Paroxetine (61869-08-7)

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