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Pharmacologic Differences Among the SSRIs: Focus on Monoamine Transporters and the HPA Axis

Published online by Cambridge University Press:  07 November 2014

Charles B. Nemeroff  and
Michael J. Owens
Charles B. Nemeroff*
Affiliation:
Dr. Nemeroff is the Reunette W. Harris Professor, and chair of the Department of Psychiatry and Behavioral Sciences at, Emory University School of Medicine in Atlanta, Georgia.
*
Department of Psychiatry and Behavioral Sciences, 101 Woodruff Circle, Woodruff Memorial Building, Atlanta, GA 30322. E-Mail:, cnemero@emory.edu
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Abstract

Depression is a widespread and serious disorder that afflicts an estimated 13.1 to 14.2 million adults in the United States each year. Even more compellingly, the lifetime prevalence rate of depression in the US has recently been estimated to include 16.2% of adults (21% women, 13% men), or >32.6 million people. There are multiple putative “causes” of depression, with approximately one-third of an individual's propensity for unipolar depression due to genetic vulnerability, while the remaining two-thirds is due to environmental factors. Although the selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to mainly act by selectively binding to the serotonin (5-HT) transporter to block reuptake of 5-HT from the synapse into the presynaptic nerve terminal, thereby increasing synaptic serotonin concentrations, some of the SSRIs also exhibit other neuropharmacologic effects. One such example is the high affinity for paroxetine in blocking norepinephrine reuptake. Another is the inhibition of dopamine reuptake by sertraline. In depression, hyperactivity of corticotropin-releasing factor (CRF)-producing neurons contribute to the well-characterized hypothalamic-pituitary-adrenal axis hyperactivity of depression. Increased activity of extrahypothalamic CRF circuits are believed to contribute to several depressive symptoms. Treatment and certain SSRIs have been shown to reduce the activity of CRF neurons and may contribute to their therapeutic action. Each SSRI apparently has its own unique pharmacologic properties that likely underlie their observed differences in clinical use.

Type
Research Article
Information
CNS Spectrums , Volume 9 , Issue S4 , 2004 , pp. 23 - 31
Copyright
Copyright © Cambridge University Press 2004

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References

1.Kessler, RC, Berglund, P, Demler, O, et al.The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289(23):3095–3105.CrossRefGoogle ScholarPubMed
2.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.Google Scholar
3.Robins, LN, Wing, J, Wittchen, H-U, et al.The Composite International Diagnostic Interview. Arch Gen Psychiatry. 1988;45:1069–1077.CrossRefGoogle ScholarPubMed
4.First, MB, Spitzer, RL, Gibbon, M, Williams, JBW. Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP). New York, NY: Biometrics Research, New York State Psychiatric Institute; 1997.Google Scholar
5.Kendler, KS. Anna-Monika-Prize paper. Major depression and the environment: a psychiatric genetic perspective. Pharmacopsychiatry. 1998;31(1):5–9.CrossRefGoogle ScholarPubMed
6.Sullivan, PF, Neale, MC, Kendler, KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000;157(10):1552–1562.Google Scholar
7.Abkevich, V, Camp, NJ, Hensel, CH, et al.Predisposition locus for major depression at chromosome 12q22-12q23.2. Am J Hum Genet. 2003;73(6):1271–1281.Google Scholar
8.Arborelius, L, Owens, MJ, Plotsky, PM, Nemeroff, CB. The role of cortiocotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999;160(1):1–12.Google Scholar
9.Ressler, KJ, Nemeroff, CB. Role of norepinephrine in the pathophysiology and treatment of mood disorders. Biol Psychiatry. 1999;46:1219–1233.CrossRefGoogle ScholarPubMed
10.Nestler, EJ, Barrot, M, DiLeone, RJ, et al.Neurobiology of depression. Neuron. 2002;34:13–25.Google Scholar
11.Delgado, PL. Depression: the case for a monoamine deficiency. J Clin Psychiatry. 2000;61:7–11.Google Scholar
12.Gutman, DA, Nemeroff, CB. Persistent central nervous system effects of an adverse early environment: clinical and preclinical studies. Physiol Behav. 2003;79(3):471–478.Google Scholar
13.Mullen, PE, Martin, JL, Anderson, JC, Romans, SE, Herbison, GP. The long-term impact of the physical, emotional, and sexual abuse of children: a community study. Child Abuse Negl. 1996;20(1):7–21.CrossRefGoogle ScholarPubMed
14.Saunders, B, Villoponteaux, L, Lipovsky, J. Child sexual assault as a risk factor for mental disorders among women: a community survey. J Interpers Violence. 1992;7:189–204.Google Scholar
15.Ruppenthal, GC, Arling, GL, Harlow, HF, Sackett, GP, Suomi, SJ. A 10-Year perspecitve of motherless-mother monkey behavior. J Abnorm Psychol. 1976;85(4):341–349.CrossRefGoogle Scholar
16.Levine, S, Wiener, SG, Coe, CL. Temporal and social factors influencing behavioral and hormonal responses to separation in mother and infant squirrel monkeys. Psychoneuroendocrinology. 1993;18(4):297–306.Google Scholar
17.Levine, SInfantile Experience and resistance to physiological stress. Science. 1975;126:405–406.CrossRefGoogle Scholar
18.Newport, DJ, Stowe, ZN, Nemeroff, CB. Parental depression: animal models of an adverse life event. Am J Psychiatry. 2002;159:1265–1283.Google Scholar
19.Vythilingam, M, Heim, C, Newport, DJ, et al.Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry. 2002;159(12):2072–2080.Google Scholar
20.Hammen, C, Davila, J, Brown, G, Ellicott, A, Gitlin, M. Psychiatric history and stress: predictors of severity of unipolar depression. J Abnormal Psychol. 1992;101(1):45–52.Google Scholar
21.Kendler, Ks, Kessler, RC, Walters, EE, et al.Stressful life events, genetic liability, and onset of an episode of major depression in women. Am J Psychiatry. 1995;152(6):833–842.Google Scholar
22.Schildkraut, JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry. 1965;122(5):509–522.Google Scholar
23.Tatsumi, M, Groshan, K, Blakely, RD, Richelson, E. Pharmacologic profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997;340:249–258.CrossRefGoogle ScholarPubMed
24.Kaplan, H, Sadock, BJ. Synopsis of Psychiatry: Behavioral Sciences, Clinical Psychiatry. 6th ed, rev. Hagerstown, MD: Lippincott, Williams, and Wilkins; 1991.Google Scholar
25.Thase, ME. Effectiveness of antidepressants: comparative remission rates. J Clin Psychiatry. 2003;64(Suppl 2):3–7.Google Scholar
26.Horwath, E, Johnson, J, Klerman, GL, et al.Depressive symptoms as relative and attributable risk factors for first-onset major depression. Arch Gen Psychiatry. 1992;49:817–823.Google Scholar
27.Judd, LL, Akiskal, HS, Paulus, MP. The role and clinical significance of subsyndromal depressive symptoms (SSD) in unipolar major depressive disorder. J Affect Disord. 1997;45:5–18.Google Scholar
28.Owens, MJ, Morgan, WN, Plott, SJ, Nemeroff, CB. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther. 1997;283(3):1305–1322.Google Scholar
29.Stahl, SM. Basic psychopharmacology of antidepressants, part 1: antidepressants have seven distinct mechanisms of action. J Clin Psychiatry. 1998;59:5–14.Google Scholar
30.Meyer, JH, Goulding, VS, Wilson, AA, Hussey, D, Christensen, BK, Houle, S. Bupropion occupancy of the dopamine transporter is low during clinical treatment. Psychopharmacology (Berl). 2002;163(1):102–105.Google Scholar
31.Learned-Coughlin, SM, Bergstrom, M, Savitcheva, I, Ascher, J, Schmith, VD, Langstrom, B. In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography. Biol Psychiatry. 2003;54(8):800–805.Google Scholar
32.Seeman, P. Receptor Tables Vol.2: Drug Dissociation Constants for Neuroreceptors and Transporters. Schizophrenia Research: Toronto, Canada; 1993.Google Scholar
33.Meyer, JH, Wilson, AA, Sagrati, S, et al.Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry. 2004;161(96):826–835.Google Scholar
34.Owens, MJ, Knight, DL, Nemeroff, CB. Paroxetine binding to the rat norephinephrine transporter in vivo. Biol Psychiatry. 2000;47:842–845.Google Scholar
35.Gilmor, ML, Owens, MJ, Nemeroff, CB. Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Am J Psychiatry. 2002;159(10):1702–1710.Google Scholar
36.Meyer, JH, Wilson, AA, Ginovaret, N, et al.Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [11C]DASB PET imaging study. Am J Psychiatry. 2001;158:1843–1849.Google Scholar
37.Watkins, L, Davidson, JRT, Connor, KM, et al.Effects of paroxetine and venlafaxine-XR on heart rate variability in depression. Poster presented at: 16th Annual Meeting of the European College of Neuropsychopharmacology; September 20-24, 2003; Prague, Czech Republic.Google Scholar
38.Carney, RM, Blumenthal, JA, Catallier, D, et al.Depression as a risk factor for mortality after acute myocardial infarction. Am J Cardiol. 2004;92(11):1277–1281.Google Scholar
39.Buckley, NA, McManus, PR. Fatal Toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ. 2002;325:1332–1333.Google Scholar
40.Ladd, CO, Huot, RL, Thrivikraman, KV, Nemeroff, CB, Plotsky, PM. Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor mRNA and negative feedback on the hypothalamo-pituitary-adrenal axis following neonatal maternal separation. Biol Psychiatry. 2004;55(4):367–375.Google Scholar
41.Holsboer, F. In: Bloom, F, Kupfer, D, eds. Psychopharmacology: The Fourth Generation of Progress. Raven Press, Ltd: New York, NY:957–999.Google Scholar