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Inhibition of Norepinephrine Uptake in Patients With Major Depression Treated With Paroxetine

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 Åsberg Depression Rating Scale score 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.

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				References PsychiatryOnline CME, May 1, 2007; 2007(1): 2 - 2. [Full Text]

				L. Leventhal, V. Smith, G. Hornby, T. H. Andree, M. R. Brandt, and K. E. Rogers Differential and Synergistic Effects of Selective Norepinephrine and Serotonin Reuptake Inhibitors in Rodent Models of Pain J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1178 - 1185. [Abstract] [Full Text] [PDF]

				H. G. RUHE, J. HUYSER, J. A. SWINKELS, and A. H. SCHENE Dose escalation for insufficient response to standard-dose selective serotonin reuptake inhibitors in major depressive disorder: Systematic review The British Journal of Psychiatry, October 1, 2006; 189(4): 309 - 316. [Abstract] [Full Text] [PDF]

				T. R Marcy and M. L Britton Antidepressant-Induced Sweating Ann. Pharmacother., April 1, 2005; 39(4): 748 - 752. [Abstract] [Full Text] [PDF]

				G. H Manos and S. M Wechsler Transient Ischemic Attack Reported with Paroxetine Use Ann. Pharmacother., April 1, 2004; 38(4): 617 - 620. [Abstract] [Full Text] [PDF]

				J. Rosack Psychiatr News, October 4, 2002; 37(19): 23 - 23. [Full Text]

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