Skip to main content Accessibility help

Efficacy of Noradrenergic-Selective Agents in the Treatment of Neuropsychiatric Diseases

  • Siegfried F. Kasper and Eva Resinger


In recent years, a number of antidepressants with varying degrees of selectivity for the noradrenergic neurotransmitter system have become available. However, these agents represent a pharmacologically heterogeneous group and differ in terms of their precise side-effect profile and, possibly, their clinical efficacy. Bupropion, which is thought to act on both the dopamine and norepinephrine (NE) systems, has not been widely used as an antidepressant and has more recently been licensed as adjunctive therapy for smoking cessation. The serotonin-NE reuptake inhibitors venlafaxine and nefazodone, the noradrenergic and specific serotonergic antide-pressant mirtazapine, and the selective NE reuptake inhibitor reboxetine (the only truly NE-selective agent available) have all demonstrated efficacy in the treatment of depressive disorders. Evidence is now emerging for their use in the treatment of anxiety and panic disorders. There is some suggestion of a role for noradrenergic agents in other disorders, including attention-deficit/hyper-activity disorder and social phobia. The full range of disorders for which noradrenergic agents can be used remains to be seen and further research in this area is necessary.


Corresponding author

Please direct correspondence to: Siegfried F. Kasper, MD, University of Vienna, Wahringer Gurtel 18-20, A-1090, Vienna, Austria. Tel: 43-1-40400-3568; Fax: 43-1-40400-3099; E-mail:


Hide All
1. Murray, CJL, Lopez, AD. A comprehensive assessment of mortality and disability from diseases, injuries and risk factors in 1990 and projected to 2020. In: The Global Burden of Disease. World Health Organization; 1998.
2. Feighner, JP. Mechanism of action of antidepressants medications. J Clin Psychiatry. 1999a; 60(Suppl 4): 413.
3. Horst, WD, Preskorn, SH. Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion. J Affect Disord. 1998; 51: 237254.
4. Anderson, IM, Tomenson, BM. The efficacy of selective serotonin re-uptake inhibitors in depression: a meta-analysis of studies against tricyclic antidepressants. J Psychopharmacol. 1994; 8: 238249.
5. Anderson, IM, Tomenson, BM. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis. Br Med J. 1995; 310: 14331438.
6. Schatzberg, AF. Clinical efficacy of reboxetine in major depression. In: Gorman, JM, Nemeroff, CB, eds. The role of norepinephrine in the treatment of depression. J Clin Psychiatry. 1999; 60: 623631.
7. Humble, M. Noradrenaline and serotonin reuptake inhibition as clinical principlies: a review of antidepressant efficacy. Acta Psychiatr Scand Suppl. 2000; 402: 2836.
8. Boyce, P, Judd, F. The place for the tricyclic antidepressants in the treatment of depression. Aust N Z J Psychiatry. 1999: 33: 323327.
9. Coupland, N, Wilson, S, Nutt, D. Antidepressant drugs and the cardiovascular system: a comparison of tricyclics and selective serotonin reuptake inhibitors and their relevance for the treatment of psychiatric patients with cardiovascular problems. J Psychopharmacol. 1997; 11: 8392.
10. Davidson, JRT, Connor, KM. Bupropion sustained release: a therapeutic overview. J Clin Psychiatry. 1998; 59(Suppl 4): 2531.
11. Hirschfeld, RM. Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs. J Clin Psychiatry. 1999; 60: 326335.
12. Croft, H, Settle, E Jr, Houser, T et al. , A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther. 1999; 21: 643658.
13. Kiev, A, Masco, HL, Wenger, TL et al. , The cardiovascular effects of bupropion and nortriptyline in depressed outpatients. Ann Clin Psychiatry. 1994; 6: 107115.
14. Weihs, KL, Settle, EC Jr, Batey, SR et al. , Bupropion sustained release versus paroxetine for the treatment of depression in the elderly. J Clin Psychiatry. 2000; 61: 196202.
15. Holliday, SM, Benfield, P. Venlafaxine: a review of its pharmacology and therapeutic potential in depression. Drugs. 1995; 49: 280294.
16. Cunningham, LA (for the Venlafaxine XR 208 Study Group). Once-daily extended release (XR) and venlafaxine immediate release in outpatients with major depression. Ann Clin Psychiatry. 1997; 14: 99106.
17. Einarson, TR, Arikian, SR, Casciano, J, Doyle, JJ. Comparison of extended-release venlafaxine, selective serotonin reuptake inhibitors and tricyclic antidepressants in the treatment of depression: a meta-analysis of randomized controlled trials. Clin Ther. 1999; 21: 296308.
18. Thase, ME. Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry. 1998; 59: 502508.
19. Augustin, BG, Cold, JA, Jann, MW. Venlafaxine and nefazodone, two pharmacologically distinct antidepressants. Pharmacotherapy. 1997; 17: 511530.
20. Gorman, JM, Sullivan, G. Noradrenergic approaches to antidepressant therapy. J Clin Psychiatry. 2000; 61(Suppl 1): 1316.
21. Guelfi, JD, White, C, Hackett, D et al. , Effectiveness of venlafaxine in patients hospitalized for major depression and melancholia. J Clin Psychiatry. 1995; 56: 450458.
22. Davis, R, Whittington, R, Bryson, HM. Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997; 53: 608636.
23. Feiger, A, Kiev, A, Shrivastava, RK. Nefazodone versus sertraline in outpatients with major depression: focus on efficacy, tolerability and effects on sexual function and satisfaction. J Clin Psychiatry. 1996; 57: 5362.
24. Feighner, J, Targum, SD, Bennett, ME et al. , A double-blind placebo-controlled trial of nefazodone in the treatment of patients hospitalized for major depression. J Clin Psychiatry. 1998; 59: 246253.
25. Kasper, S, El-Giamal, N, Hilger, E. Reboxetine: the first selective noradrenaline reuptake inhibitor (selective NRI). Expert Opin Pharmacother. 2000; 1: 771782.
26. Holm, KJ, Spencer, CM. Reboxetine: a review of its use in depression. CNS Drugs. 1999; 12: 6683.
27. Montgomery, SA. Reboxetine: additional benefits to the depressed patient. J Psychopharmacol. 1997; 11(Suppl 1): S9–S15.
28. Kasper, S. Treatment benefits of reboxetine. International Journal of Psychiatry in Clinical Practice. 1999; 3: S3–S8.
29. Dubini, A, Bose, M, Polin, V. Noradrenaline-selective versus serotonin-selective antidepressant therapy: differential effects on social functioning. J Psychopharmacol. 1997; 11: S17–S23.
30. Versiani, M, Mehilane, L, Gaszner, P et al. , Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder. J Clin Psychiatry. 1999; 60: 400406.
31. Versiani, M. Reboxetine, a novel selective NRI, in the treatment of panic disorder [Abstract P.I.067]. Eur Neuropsychopharmacol. 2000; 10 (Suppl 3): 245.
32. Holm, KJ, Markham, A. Mirtazapine. a review of its use in major depression. Drugs. 1999; 57: 607631.
33. Scates, AC, Doraiswamy, PM. Reboxetine: a selective norepinephrine reuptake inhibitor for the treatment of depression. Ann Pharmacother. 2000; 34: 13021312.
34. Mucci, M. Reboxetine: a review of antidepressant tolerability. J Psychopharmacol. 1997; 11 (Suppl 4): S33–S37.
35. Montgomery, SA. Predicting response: noradrenaline reuptake inhibition. Int Clin Psychopharmacol. 1999; 14: S21–S26.
36. Montgomery, SA, Reimitz, PE, Zivkov, M. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study. Int Clin Psychopharmacol. 1998; 13: 6373
37. Schatzberg, AF. New indications for antidepressants. J Clin Psychiatry. 2000; 61(Suppl 11): 917.
38. Feighner, JP. Overview of antidepressants currently used to treat anxiety disorders. J Clin Psychiatry. 1999b; 60(Suppl 22): 1822.
39. Sheehan, DV. Venlafaxine extended release (XR) in the treatment of generalized anxiety disorder. J Clin Psychiatry. 1999; 60(Suppl 22): 2328.
40. Gorman, JM. The use of newer antidepressants for panic disorder. J Clin Psychiatry. 1997; 58(Suppl 14): 5459.
41. Falkai, P. Mirtazapine: other indications. J Clin Psychiatry. 1999; 60(Suppl 17): 3639.
42. Papp, LA, Coplan, JD, Martinez, JM et al. , Efficacy of open-label nefazodone treatment in patients with panic disorder. J Clin Psychopharmacol. 2000; 20: 544546.


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed