This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Basal and Desipramine-Induced Alterations in Plasma Norepinephrine Kinetics

Richard C. Veith, MD; Nancy Lewis, RN; Oscar A. Linares, MD; Robert F. Barnes, MD; Murray A. Raskind, MD; Enrique C. Villacres, MD; M. Michele Murburg, MD; E. Alexandra Ashleigh, MD; Sonia Castillo, PhD; Elaine R. Peskind, MD; Marcella Pascualy, MD; Jeffrey B. Halter, MD

Arch Gen Psychiatry. 1994;51(5):411-422.

Abstract
Background
To determine whether elevations of plasma norepinephrine (NE) in major depression represent increased sympathetic nervous system (SNS) activity and to assess the effects of desipramine hydrochloride on sympathetic function.

Methods
SNS activity was assessed in depressed patients and controls by an isotope-dilution, plasma NE Kinetic technique using mathematical modeling and compartmental analysis. This approach provided estimates of the rate of NE appearance into an extravascular compartment, which is the site of endogenous NE release from SNS nerves, the corresponding rate of NE appearance into plasma, and the rate of NE clearance from plasma.

Results
Norepinephrine appearance into the extravascular and vascular compartments was significantly elevated in 17 depressed patients compared with that in 36 controls. The rate of NE clearance from plasma was similar in both groups. This is compatible with increased SNS activity in major depression. Desipramine, given for 2 days, significantly reduced the concentration of NE in plasma of patients and controls by markedly suppressing the rates of extravascular and vascular NE appearance, compatible with a short-term reduction in SNS activity. Desipramine prolonged the rate of NE clearance from plasma, consistent with a blockade of NE re-uptake into SNS nerve terminals. The initial suppression of SNS activity by desipramine was reversed by long-term (28 days) treatment of patients, with extravascular and vascular NE appearance rates returning to approximately basal levels. An associated rise in plasma NE concentrations compared with the baseline was attributable to a progressive reduction in plasma NE clearance.

Conclusion
Sympathetic nervous system activity is elevated in major depression and is suppressed by short-term desipramine administration. The demonstration of SNS reactivation occurring with prolonged desipramine treatment is compatible with the theory that long-term treatment desensitizes CNS ₂-adrenergic receptors and emphasizes the value of examining the temporal course of responses to pharmacological challenges of neuroendocrine systems. Previously reported elevations of plasma NE during prolonged administration of tricyclic antidepressants are probably the result of a reduction in plasma NE clearance, not an increase in SNS activity.

Author Affiliations
From the Geriatric Research, Education, and Clinical Center (GRECC) (Drs Veith, Raskind, and Castillo and Ms Lewis) and Psychiatry Service (Drs Barnes, Villacres, Murburg, Ashleigh, Peskind, and Pascualy), Seattle (Wash) VAMC; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle (Drs Veith, Raskind, Barnes, Villacres, Murburg, Ashleigh, Peskind, and Pascualy); GRECC, Ann Arbor (Mich) VAMC (Drs Linares and Halter); and the Division of Geriatric Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (Drs Linares and Halter).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Depression and heart rate variability in patients with coronary heart disease
CARNEY and FREEDLAND
Cleveland Clinic Journal of Medicine 2009;76:S13-S17.
ABSTRACT | FULL TEXT  

The influences of depression and venlafaxine use at therapeutic doses on atrial conduction
Emul et al.
J Psychopharmacol 2009;23:163-167.
ABSTRACT  

Association Between Major Depressive Disorder and Heart Rate Variability in the Netherlands Study of Depression and Anxiety (NESDA)
Licht et al.
Arch Gen Psychiatry 2008;65:1358-1367.
ABSTRACT | FULL TEXT  

Biobehavioral Influences on Matrix Metalloproteinase Expression in Ovarian Carcinoma
Lutgendorf et al.
Clin. Cancer Res. 2008;14:6839-6846.
ABSTRACT | FULL TEXT  

Hindlimb unloading elicits anhedonia and sympathovagal imbalance
Moffitt et al.
J. Appl. Physiol. 2008;105:1049-1059.
ABSTRACT | FULL TEXT  

Nighttime Heart Rate and Survival in Depressed Patients Post Acute Myocardial Infarction
Carney et al.
Psychosom. Med. 2008;70:757-763.
ABSTRACT | FULL TEXT  

Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation, and endothelial function
Pizzi et al.
Eur Heart J 2008;29:1110-1117.
ABSTRACT | FULL TEXT  

Pituitary-Adrenal and Sympathetic Nervous System Responses to Stress in Women Remitted From Recurrent Major Depression
Ahrens et al.
Psychosom. Med. 2008;70:461-467.
ABSTRACT | FULL TEXT  

Pheochromocytoma: an update on genetics and management
Karagiannis et al.
Endocr Relat Cancer 2007;14:935-956.
ABSTRACT | FULL TEXT  

Adrenal Incidentaloma, Borderline Elevations of Urine or Plasma Metanephrine Levels, and the "Subclinical" Pheochromocytoma
Lee et al.
Arch Surg 2007;142:870-874.
ABSTRACT | FULL TEXT  

Coronary Artery Disease and Depression: Patients With More Depressive Symptoms Have Lower Cardiovascular Reactivity During Laboratory-Induced Mental Stress
York et al.
Psychosom. Med. 2007;69:521-528.
ABSTRACT | FULL TEXT  

Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study
Otte et al.
Am. J. Psychiatry 2005;162:2139-2145.
ABSTRACT | FULL TEXT  

Quality of Life Following Cardiac Surgery: Impact of the Severity and Course of Depressive Symptoms
Goyal et al.
Psychosom. Med. 2005;67:759-765.
ABSTRACT | FULL TEXT  

Effects of Antidepressant Medication on Morbidity and Mortality in Depressed Patients After Myocardial Infarction
Taylor et al.
Arch Gen Psychiatry 2005;62:792-798.
ABSTRACT | FULL TEXT  

Depressive Symptoms and Heart Rate Variability in Postmenopausal Women
Kim et al.
Arch Intern Med 2005;165:1239-1244.
ABSTRACT | FULL TEXT  

Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia
Gold et al.
Proc. Natl. Acad. Sci. USA 2005;102:8303-8308.
ABSTRACT | FULL TEXT  

Depression, the Autonomic Nervous System, and Coronary Heart Disease
Carney et al.
Psychosom. Med. 2005;67:S29-S33.
ABSTRACT | FULL TEXT  

Relation between psychological strain and carotid atherosclerosis in a general population
Wolff et al.
Heart 2005;91:460-464.
ABSTRACT | FULL TEXT  

Clinical Assessment of Norepinephrine Transporter Blockade Through Biochemical and Pharmacological Profiles
Vincent et al.
Circulation 2004;109:3202-3207.
ABSTRACT | FULL TEXT  

Mental Health in an Aging Population: The NIMH Perspective
Hyman
Focus 2004;2:282-287.
FULL TEXT  

Depressive Symptoms Are Related to Higher Ambulatory Blood Pressure in People With a Family History of Hypertension
Grewen et al.
Psychosom. Med. 2004;66:9-16.
ABSTRACT | FULL TEXT  

Biochemical Diagnosis of Pheochromocytoma: How to Distinguish True- from False-Positive Test Results
Eisenhofer et al.
J. Clin. Endocrinol. Metab. 2003;88:2656-2666.
ABSTRACT | FULL TEXT  

Desipramine attenuates loss of cardiac sympathetic neurotransmitters produced by congestive heart failure and NE infusion
Liang et al.
Am. J. Physiol. Heart Circ. Physiol. 2003;284:H1729-H1736.
ABSTRACT | FULL TEXT  

Effects of Depression on QT Interval Variability After Myocardial Infarction
Carney et al.
Psychosom. Med. 2003;65:177-180.
ABSTRACT | FULL TEXT  

The effects of reboxetine, a noradrenaline reuptake inhibitor, on the plasma noradrenaline response to a cold pressor test in healthy volunteers
Kelly et al.
J Psychopharmacol 2002;16:333-336.
ABSTRACT  

Depression and Risk of Heart Failure Among the Elderly: A Prospective Community-Based Study
Williams et al.
Psychosom. Med. 2002;64:6-12.
ABSTRACT | FULL TEXT  

Depression, Heart Rate Variability, and Acute Myocardial Infarction
Carney et al.
Circulation 2001;104:2024-2028.
ABSTRACT | FULL TEXT  

Depressive symptoms and risk of functional decline and death in patients with heart failure
Vaccarino et al.
J Am Coll Cardiol 2001;38:199-205.
ABSTRACT | FULL TEXT  

Effects of Psychological Stress and Psychiatric Disorders on Blood Coagulation and Fibrinolysis: A Biobehavioral Pathway to Coronary Artery Disease?
von Kanel et al.
Psychosom. Med. 2001;63:531-544.
ABSTRACT | FULL TEXT  

Reduced Brain Norepinephrine and Dopamine Release in Treatment-Refractory Depressive Illness: Evidence in Support of the Catecholamine Hypothesis of Mood Disorders
Lambert et al.
Arch Gen Psychiatry 2000;57:787-793.
ABSTRACT | FULL TEXT  

Cardiovascular Stress Responses and Their Relation to Symptoms in Gulf War Veterans With Fatiguing Illness
Peckerman et al.
Psychosom. Med. 2000;62:509-516.
ABSTRACT | FULL TEXT  

Negative Affect as a Prospective Risk Factor for Hypertension
Jonas and Lando
Psychosom. Med. 2000;62:188-196.
ABSTRACT | FULL TEXT  

Psychopharmacology
Cameron
Psychosom. Med. 1999;61:585-590.
FULL TEXT  

Can Treating Depression Reduce Mortality After an Acute Myocardial Infarction?
Carney et al.
Psychosom. Med. 1999;61:666-675.
ABSTRACT | FULL TEXT  

A 69-Year-Old Man With Anger and Angina
Williams
JAMA 1999;282:763-770.
FULL TEXT  

Impact of Psychological Factors on the Pathogenesis of Cardiovascular Disease and Implications for Therapy
Rozanski et al.
Circulation 1999;99:2192-2217.
ABSTRACT | FULL TEXT  

Sympathoadrenal Hyperactivity and the Etiology of Neuroleptic Malignant Syndrome
Gurrera
Am. J. Psychiatry 1999;156:169-180.
ABSTRACT | FULL TEXT  

Depression Is a Risk Factor for Coronary Artery Disease in Men: The Precursors Study
Ford et al.
Arch Intern Med 1998;158:1422-1426.
ABSTRACT | FULL TEXT  

The Relationship of Depression to Cardiovascular Disease: Epidemiology, Biology, and Treatment
Musselman et al.
Arch Gen Psychiatry 1998;55:580-592.
ABSTRACT | FULL TEXT  

Are Symptoms of Anxiety and Depression Risk Factors for Hypertension? Longitudinal Evidence From the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study
Jonas et al.
Arch Fam Med 1997;6:43-49.
ABSTRACT