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Noradrenaline (Norepinephrine) and Depression

Role in Aetiology and Therapeutic Implications

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Abstract

In the pharmacological treatment of depression the focus has recently shifted from serotonin (5-hydroxytryptamine; 5-HT) to noradrenaline (norepinephrine), with the advent of new antidepressants such as noradrenaline reuptake inhibitors, noradrenergic and selective serotonergic antidepressants, and serotonin/noradrenaline reuptake inhibitors. It has been suggested that noradrenergic compounds may prove to have beneficial activity in those depressions that are characterised by a ‘noradrenergic deficiency syndrome’, which is clinically manifested through emotional withdrawal, psychomotor retardation, as well as concentration and memory deficits.

The role of noradrenergic mechanisms in the aetiology of depression has been assumed since the catecholamine hypothesis, based on the inhibitory action of tricyclic antidepressants and monoamine oxidase inhibitors on noradrenaline uptake, was formulated. In this article, the aetiological significance of noradrenaline in depression is discussed with regard to the anatomical basis of the noradrenergic system (the locus caeruleus), noradrenaline metabolites, noradrenergic receptors, some aspects of thyroid function and the hypothalamic-pituitary-adrenal axis.

The efficacy and tolerability profiles of new antidepressant compounds reboxetine, milnacipran, mirtazapine and venlafaxine are discussed in view of their noradrenergic activity.

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References

  1. Angst J. Epidemiology of depression. Psychopharmacology 1992; 106: 71–4

    Article  Google Scholar 

  2. Schildkraut JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 1965; 122: 509–22

    PubMed  CAS  Google Scholar 

  3. van Praag HM, Korf J. Endogenous depression with and without disturbances of 5-HT metabolism: a biochemical classification? Psychopharmacology 1971; 19: 148–52

    Article  Google Scholar 

  4. Coppen A. Defects in monoamine metabolism and their possible importance in the pathogenesis of depressive syndromes. Psychiatr Neurol Neurochir 1969; 72(2): 173–80

    PubMed  CAS  Google Scholar 

  5. Stone TW. CNS neurotransmitters. In: Stone TW, editor. Neuropharmacology. New York (NY): WH Freedman and Company Limited — Spectrum, 1995: 44–64 (Biochemical & medicinal chemistry series)

    Google Scholar 

  6. Anand A, Charney DS. Catecholamines in depression. In: Honig A, Van Praag HM, editors. Depression: neurobiological, psychopathological and therapeutic advances. Chichester: John Wiley & Sons, 1997: 147–78

    Google Scholar 

  7. Brunello N, Racagni G. Rationale for the development of na reuptake inhibitors. Hum Psychopharmacol 1998; 13: S13–S19

    Article  CAS  Google Scholar 

  8. Leonard BE. Noradrenaline in basic models of depression. Eur Neuropsychopharmacol 1997; 7 Suppl. 1: S11–S16

    Article  PubMed  CAS  Google Scholar 

  9. Leonard BE. Fundamentals of psychophannacology. Chichester: John Wiley & Sons, 1997: 111–8

    Google Scholar 

  10. Checkley S. Biological models of depression and response to antidepressant treatments. In: Checkley S, editor. The management of depression. Oxford: Blackwell Science Ltd, 1998: 42–69

    Google Scholar 

  11. Cheetham SC, Katona CLE, Horton RW. Post-mortem studies of neurotransmitter biochemistry in depression and suicide. In: Horton R, Katona CLE, editors. London: Academic Press Ltd, 1991: 192–221

  12. Mann JJ, Stanley M, McBride PA, et al. Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 1986; 43: 954–9

    Article  PubMed  CAS  Google Scholar 

  13. Nutt DJ, Holman RB, Thomas DN. Noradrenergic mechanisms in anxiolytic and antidepressant drug action. In: Elliott JM, Healy DL, Marsden CA, editors. Experimental approaches to anxiety and depression. Chichester: John Wiley & Sons, 1992

    Google Scholar 

  14. Nelson JC. Synergistic benefits of serotonin and noradrenaline reuptake inhibition. Depress Anxiety 1998; 7 Suppl. 10: 5–6

    Article  Google Scholar 

  15. Baron BM, Ogden AM, Siegel BW, et al. Rapid downregulation of beta-adrenoreceptors by co-administration of desipramine and fluoxetine. Eur J Pharmacol 1988; 154(2): 125–34

    Article  PubMed  CAS  Google Scholar 

  16. Redmond AM, Leonard BE. An evaluation of the role of the noradrenergic system in the neurobiology of depression: a review. Hum Psychopharmacol 1997; 12(5): 407–30

    Article  CAS  Google Scholar 

  17. Kelly CK, Cooper SJ. Plasma noradrenaline response to electroconvulsive therapy in depressive illness. Br J Psychiatry 1997; 171: 182–6

    Article  PubMed  CAS  Google Scholar 

  18. Siever LJ, Coccano E, Davis KL. Hormone response to noradrenergic challenge. In: Halbreich U, Rose R, editors. Hormones in depression. New York (NY): Raven Press, 1986: 59–73

    Google Scholar 

  19. Brown SL, Steinberg RL, van Praag HM. The pathogenesis of depression: reconsideration of neurotransmitter data. In: den Boer JA, Sitsen JMA, editors. Handbook of depression and anxiety — a biological approach. New York (NY): Marcel Dekker, Inc., 1994: 317–47

    Google Scholar 

  20. Delgado PL, Charney DS, Price LH, et al. Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 1990; 47: 411–8

    Article  PubMed  CAS  Google Scholar 

  21. Miller HL, Delgado PL, Salomon RM, et al. Clinical and biochemical effects of catecholamine depletion on anti-depressant—induced remission of depression. Arch Gen Psychiatry 1996; 53: 117–28

    Article  PubMed  CAS  Google Scholar 

  22. Delgado PL, Price LH, Miller HL, et al. Rapid serotonin depletion as a provocative challenge test for patients with major depression: relevance to antidepressant action and the neurobiology of depression. Psychopharmacol Bull 1991; 27: 321–30

    PubMed  CAS  Google Scholar 

  23. Delgado PL, Miller HL, Salomon RM, et al. Monoamines and the mechanism of antidepressant action: effects of catecholamine depletion on mood of patients treated with antidepressants. Psychopharmacol Bull 1993; 29: 389–96

    PubMed  CAS  Google Scholar 

  24. Montgomery SA. Is there a role for a pure noradrenergic drug in the treatment of depression? Eur Neuropsychopharmacol 1997; 7 Suppl. 1: S3–S9

    Article  PubMed  CAS  Google Scholar 

  25. Holm KJ, Spencer CM. Reboxetine. A review of its use in major depression. Drugs 1999; 12(1): 65–83

    CAS  Google Scholar 

  26. Montgomery SA. Reboxetine: additional benefits to the depressed patient. J Psychopharmacol 1997; 11(4) Suppl. : S9–S15

    PubMed  CAS  Google Scholar 

  27. Burrows CD, Maguire KP, Noman TR. Antidepressant efficacy and tolerability of the selective norepinephrine reuptake inhibitor reboxetine: a review. J Clin Psychiatry 1998; 58 Suppl. 14: 4–7

    Google Scholar 

  28. Massana J. Reboxetine versus fluoxetine: an overview of efficacy and tolerability. J Clin Psychiatry 1998; 59 Suppl. 1: S20–39

    Google Scholar 

  29. Ban TA, Gaszner P, Aguglia E, et al. Clinical efficacy of reboxetine: a comparative study with desipramine, with methodological considerations. Hum Psychopharm 1998 Feb; 13 Suppl. 1: S20–39

    Google Scholar 

  30. Berzewski H, Van Moffaert M, Cagiano CA. Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive episode. Eur Neuropsychopharmacol 1997; 7(1): 37–47

    Article  Google Scholar 

  31. Mucci M. Reboxetine: a review of antidepressant tolerability. J Psychopharmacol 1997; 11: 33–7

    Google Scholar 

  32. Briley M. From dirty drugs to hyperselectivity and part way back again. Hum Psychopharmacol 1997; 12: 121–5

    Article  Google Scholar 

  33. Holm KJ, Markham A. Mirtazapine. Areview of its use in major depression. Drugs 1999; 57(4): 607–31

    CAS  Google Scholar 

  34. Smith WT, Glaudin V, Panagides J. Mirtazapine vs amitriptyline vs placebo in the treatment of major depressive disorder. Psychopharmacol Bull 1990; 26: 191–6

    PubMed  CAS  Google Scholar 

  35. Van Moffaert M, de Wilde J, Dierick M, et al. Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression. Int J Clin Psychopharmacol 1995; 10: 3–9

    Article  Google Scholar 

  36. Dierick M. Areview of the efficacy and tolerability of venlafaxine. Eur Psychiatry 1997; 12 Suppl. 3: 15–25

    Google Scholar 

  37. Dierick M. An open-label evaluation of the long-term safety of oral venlafaxine in depressed elderly patients. Ann Clin Psychiatry 1996; 8(3): 169–78

    Article  PubMed  CAS  Google Scholar 

  38. Holliday SM, Benfield P. Venlafaxine. A review of its pharmacology and therapeutic potential in depression. Drugs 1995; 49(2): 282–94

    Google Scholar 

  39. Preskorn SH. Pharmacotherapeutic profile of venlafaxine. Eur Psychiatry 1997; 12 Suppl. 4: 285–94

    Article  Google Scholar 

  40. Spencer CM, Wilde MI. Milnacipram. A review of its use in depression. Drugs 1998; 56(3): 405–27

    CAS  Google Scholar 

  41. Schatzberg AF, Schildkraut JJ. Recent studies on norepinephrine systems in mood disorders. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: the fourth generation of progress. New York (NY): Raven Press, 1995: 911–20

    Google Scholar 

  42. Healy D. The antidepressant era. Cambridge (MA): Harvard University Press, 1997

    Google Scholar 

  43. Van Moffaert M, Jannes C. An update of panic disorders, somatization, biological markers and outcome. Acta Psychiatrica Belg 1987; (3): 332-45

  44. Weissman MM. Beyond symptoms: social functioning and the new antidepressants. J Pharmacol 1977; 11(4): 5–8

    Google Scholar 

  45. Ansseau M, Bataille M, Van Moffaert M, et al. Controlled comparison of tianeptine, alprazolam and mianserin in the treatment of adjustment disorders with anxiety and depression. Hum Psychopharmacol 1996; 11; 293–8

    Article  CAS  Google Scholar 

  46. van Praag HM. Concerns about depression. Eur Psychiatry 1995; 10(6): 269–76

    Article  PubMed  Google Scholar 

  47. Dierick M, Van Moffaert M. Depressie en serotonine. Belg Tijdschr Geneesk 1994; 50(4): 293–8

    Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry and Psychosomatic Medicine, University Hospital, University of Ghent, De Pintelaan 185, 9000, Gent, Belgium

    Myriam Van Moffaert & Michel Dierick

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  1. Myriam Van Moffaert
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  2. Michel Dierick
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Correspondence to Myriam Van Moffaert.

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Van Moffaert, M., Dierick, M. Noradrenaline (Norepinephrine) and Depression. Mol Diag Ther 12, 293–305 (1999). https://doi.org/10.2165/00023210-199912040-00004

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