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Adrenoceptor Blockers

Influence on Depression and Anxiety

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Brain and Heart Dynamics

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Abstract

The prominent role of norepinephrine in the regulation of cognitive functions is suggested by the distribution of noradrenergic circuits in specific regions of the central nervous system. Adrenergic receptors play a role in the regulation of the noradrenergic system in the central nervous system, both at pre- and postsynaptic levels, and their modulation permits a dynamic system to respond and adapt to stimuli. Evidence suggests that norepinephrine system dysregulation is a mechanism involved in the occurrence of pathological anxiety and depression. The stimulated adrenergic activity in the central nervous system provides a rationale for the use of antiadrenergic medications. Studies support antagonism of the postsynaptic α1-adrenergic receptor as a target for post-traumatic stress disorder treatment.

Pharmacological action of epinephrine/norepinephrine on the heart and vessels is a basis of backbone medical therapies of cardiovascular diseases. A link between depression and the use of β-blockers has been postulated for a long time, but the association between their use and depression remains debated with conflicting results reported.

Future research will help to clarify the role of adrenergic system in mood and anxiety disorders in order to develop new treatments that not only alleviate symptoms but also affect underlying pathophysiology of these maladies.

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References

  1. Berridge CW, Waterhouse BD. The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev. 2003;42:33–84.

    PubMed  Google Scholar 

  2. Moret C, Briley M. The importance of norepinephrine in depression. Neuropsychiatr Dis Treat. 2011;7:9–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006;8:383–95.

    PubMed  PubMed Central  Google Scholar 

  4. Dohlman HG, Thorner J, Caron MG, Lefkowitz RJ. Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem. 1991;60:653–88.

    CAS  PubMed  Google Scholar 

  5. Bylund DB, Eikenberg DC, Hieble JP, Langer SZ, Lefkowitz RJ, Minneman KP, et al. International Union of Pharmacology nomenclature of adrenoceptors. Pharmacol Rev. 1994;46:121–36.

    CAS  PubMed  Google Scholar 

  6. Hieble JP, Bylund DB, Clarke DE, Eikenburg DC, Langer SZ, Lefkowitz RJ, et al. International Union of Pharmacology. X. Recommendation for nomenclature of alpha 1-adrenoceptors: consensus update. Pharmacol Rev. 1995;47:267–70.

    CAS  PubMed  Google Scholar 

  7. Berridge MJ, Irvine RF. Inositol phosphates and cell signalling. Nature. 1989;341:197–205.

    CAS  PubMed  Google Scholar 

  8. Ruffolo RR Jr, Hieble JP. Alpha-adrenoceptors. Pharmacol Ther. 1994;61:1–64.

    CAS  PubMed  Google Scholar 

  9. Knaus AE, Muthig V, Schickinger S, Moura E, Beetz N, Gilsbach R, Hein L. Alpha2-adrenoceptor subtypes – unexpected functions for receptors and ligands derived from gene-targeted mouse models. Neurochem Int. 2007;51:277–81.

    CAS  PubMed  Google Scholar 

  10. Hein L, Altman JD, Kobilka BK. Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission. Nature. 1999;402:181–4.

    CAS  PubMed  Google Scholar 

  11. O’Donnell JM. Effect of the beta-2 adrenergic agonist zinterol on norepinephrine turnover. Res Commun Chem Pathol Pharmacol. 1993;80:113–6.

    PubMed  Google Scholar 

  12. Delfs JM, Zhu Y, Druhan JP, Aston-Jones GS. Origin of noradrenergic afferents to the shell subregion of the nucleus accumbens: anterograde and retrograde tract-tracing studies in the rat. Brain Res. 1998;806:127–40.

    CAS  PubMed  Google Scholar 

  13. Borodovitsyna O, Flamini M, Chandler D. Noradrenergic modulation of cognition in health and disease. Neural Plast. 2017;2017:6031478.

    PubMed  PubMed Central  Google Scholar 

  14. Arnsten AF. Stress weakens prefrontal networks: molecular insults to higher cognition. Nat Neurosci. 2015;18:1376–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Goddard AW, Ball SG, Martinez J, Robinson MJ, Yang CR, Russell JM, Shekhar A. Current perspectives of the roles of the central norepinephrine system in anxiety and depression. Depress Anxiety. 2010;27: 339–50.

    CAS  PubMed  Google Scholar 

  16. Berridge CW. Noradrenergic modulation of arousal. Brain Res Rev. 2008;58:1–17.

    CAS  PubMed  Google Scholar 

  17. Nicholas AP, Pieribone VA, Hokfelt T. Cellular localization of messenger RNA for beta-1 and beta-2 adrenergic receptors in rat brain: an in situ hybridization study. Neuroscience. 1993;56:1023–39.

    CAS  PubMed  Google Scholar 

  18. Stone EA, John SM. Further evidence for a glial localization of rat cortical beta-adrenoceptors: studies of in vivo cyclic AMP responses to catecholamines. Brain Res. 1991;549:78–82.

    CAS  PubMed  Google Scholar 

  19. Drevets WC, Bogers W, Raichle ME. Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacol. 2002;12: 527–44.

    CAS  PubMed  Google Scholar 

  20. Ross RJ, Ball WA, Sullivan KA, Caroff SN. Sleep disturbance as the hallmark of posttraumatic stress disorder. Am J Psychiatry. 1989;146:697–707.

    CAS  PubMed  Google Scholar 

  21. Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW, et al. Biological studies of posttraumatic stress disorder. Nat Rev Neurosci. 2012;13:769–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Arnsten AF, Raskind MA, Taylor FB, Connor DF. The effects of stress exposure on prefrontal cortex: translating basic research into successful treatments for post-traumatic stress disorder. Neurobiol Stress. 2015;1:89–99.

    PubMed  Google Scholar 

  23. Togno J, Eaton S. Is there a role for prazosin in the treatment of post-traumatic stress disorder? Aust Family Physician. 2015;44:647–9.

    Google Scholar 

  24. Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003;160:371–3.

    PubMed  Google Scholar 

  25. Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D, et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007;61:928–34.

    CAS  PubMed  Google Scholar 

  26. Taylor FB, Martin P, Thompson C, Williams J, Mellman TA, Gross C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008;63:629–32.

    CAS  PubMed  Google Scholar 

  27. Germain A, Richardson R, Moul DE, Mammen O, Haas G, Forman SD, et al. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US military veterans. J Psychosom Res. 2012;72:89–96.

    PubMed  Google Scholar 

  28. Raskind MA, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013;170:1003–10.

    PubMed  Google Scholar 

  29. Ahmadpanah M, Sabzeiee P, Hosseini SM, Torabian S, Haghighi M, Jahangard L, et al. Comparing the effect of prazosin and hydroxyzine on sleep quality in patients suffering from posttraumatic stress disorder. Neuropsychobiology. 2014;69:235–42.

    CAS  PubMed  Google Scholar 

  30. Raskind MA, Peskind ER, Chow B, Harris C, Davis-Karim A, Holmes HA, et al. Trial of prazosin for post-traumatic stress disorder in military veterans. N Engl J Med. 2018;378:507–17.

    CAS  PubMed  Google Scholar 

  31. Connerney I, Shapiro PA, McLaughlin JS, Bagiella E, Sloan RP. Relation between depression after coronary artery bypass surgery and 12-month outcome: a prospective study. Lancet. 2001;358:1766–71.

    CAS  PubMed  Google Scholar 

  32. Konstam V, Moser DK, De Jong MJ. Depression and anxiety in heart failure. J Card Fail. 2005;11:455–63.

    PubMed  Google Scholar 

  33. van Melle JP, de Jonge P, Spijkerman TA, Tijssen JG, Ormel J, van Veldhuisen DJ, et al. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis. Psychosom Med. 2004;66:814–22.

    PubMed  Google Scholar 

  34. Ko DT, Hebert PR, Coffey CS, Sedrakyan A, Curtis JP, Krumholz HM. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA. 2002;288:351–7.

    CAS  PubMed  Google Scholar 

  35. McNeil GN, Shaw PK, Dock DS. Substitution of atenolol for propranolol in a case of propranolol-related depression. Am J Psychiatry. 1982;139:1187–8.

    CAS  PubMed  Google Scholar 

  36. Oppenheim G. Propranolol-induced depression: mechanism and management. Aust N Z J Psychiatry. 1983;17:400–2.

    CAS  PubMed  Google Scholar 

  37. Thiessen BQ, Wallace SM, Blackburn JL, Wilson TW, Bergman U. Increased prescribing of antidepressants subsequent to beta-blocker therapy. Arch Intern Med. 1990;150:2286–90.

    CAS  PubMed  Google Scholar 

  38. Hallas J. Evidence of depression provoked by cardiovascular medication: a prescription sequence symmetry analysis. Epidemiology. 1996;7:478–84.

    CAS  PubMed  Google Scholar 

  39. Steiner SS, Friedhoff AJ, Wilson BL, Wecker JR, Santo JP. Antihypertensive therapy and quality of life: a comparison of atenolol, captopril, enalapril and propranolol. J Hum Hypertens. 1990;4:217–25.

    CAS  PubMed  Google Scholar 

  40. Verbeek DE, van Riezen J, de Boer RA, van Melle JP, de Jonge P. A review on the putative association between beta-blockers and depression. Heart Fail Clin. 2011;7:89–99.

    PubMed  Google Scholar 

  41. Boal AH, Smith DJ, McCallum L, Muir S, Touyz RM, Dominiczak AF, Padmanabhan S. Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders. Hypertension. 2016;68:1132–8.

    CAS  PubMed  Google Scholar 

  42. Dimsdale JE, Newton RP, Joist T. Neuropsychological side effects of beta-blockers. Arch Intern Med. 1989;149:514–25.

    CAS  PubMed  Google Scholar 

  43. Paykel ES, Fleminger R, Watson JP. Psychiatric side effects of antihypertensive drugs other than reserpine. J Clin Psychopharmacol. 1982;2:14–39.

    CAS  PubMed  Google Scholar 

  44. Carruthers SG. Adverse effects of alpha 1-adrenergic blocking drugs. Drug Saf. 1994;11:12–20.

    CAS  PubMed  Google Scholar 

  45. MacDonald R, Wilt TJ, Howe RW. Doxazosin for treating lower urinary tract symptoms compatible with benign prostatic obstruction: a systematic review of efficacy and adverse effects. BJU Int. 2004;94: 1263–70.

    CAS  PubMed  Google Scholar 

  46. Guay DR. Extended-release alfuzosin hydrochloride: a new alpha adrenergic receptor antagonist for symptomatic benign prostatic hyperplasia. Am J Geriatr Pharmacother. 2004;2:14–23.

    CAS  PubMed  Google Scholar 

  47. Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR. Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol Psychiatry. 2003;54:947–9.

    CAS  PubMed  Google Scholar 

  48. Fleminger S, Greenwood RJ, Oliver DL. Pharmacological management for agitation and aggression in people with acquired brain injury. Cochrane Database Syst Rev. 2003;1:CD003299.

    Google Scholar 

  49. Fava M. Psychopharmacologic treatment of pathologic aggression. Psychiatr Clin North Am. 1997;20: 427–51.

    CAS  PubMed  Google Scholar 

  50. Sachdev PS. Neuroleptic-induced movement disorders: an overview. Psychiatr Clin North Am. 2005;28: 255–74.

    PubMed  Google Scholar 

  51. Horwitz RI, Gottlieb LD, Kraus ML. The efficacy of atenolol in the outpatient management of the alcohol withdrawal syndrome. Results of a randomized clinical trial. Arch Intern Med. 1989;149:1089–93.

    CAS  PubMed  Google Scholar 

  52. Artigas F, Romero L, de Montigny C, Blier P. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci. 1996;19:378–83.

    CAS  PubMed  Google Scholar 

  53. Ballesteros J, Callado LF. Effectiveness of pindolol plus serotonin uptake inhibitors in depression: a meta-analysis of early and late outcomes from randomised controlled trials. J Affect Disord. 2004;79:137–47.

    CAS  PubMed  Google Scholar 

  54. Nguyen KQ, Tohyama Y, Watanabe A, Hasegawa S, Skelin I, Diksic M. Acute effects of combining citalopram and pindolol on regional brain serotonin synthesis in sham operated and olfactory bulbectomized rats. Neurochem Int. 2009;54:161–71.

    CAS  PubMed  Google Scholar 

  55. Berney A, Nishikawa M, Benkelfat C, Debonnel G, Gobbi G, Diksic M. An index of 5-HT synthesis changes during early antidepressant treatment: alpha-[11C]methyl-L-tryptophan PET study. Neurochem Int. 2008;52:701–8.

    CAS  PubMed  Google Scholar 

  56. Portella MJ, de Diego-Adeliño J, Puigdemont D, Pérez-Egea R, Alvarez E, Artigas F, Pérez V. Pindolol augmentation enhances response outcomes in first depressive episodes. Eur Neuropsychopharmacol. 2009;19:516–9.

    CAS  PubMed  Google Scholar 

  57. Liu Y, Zhou X, Zhu D, Chen J, Qin B, Zhang Y, et al. Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis. Hum Psychopharmacol. 2015;30:132–42.

    PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Experimental Medicine, Section of Pharmacology, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Donato Cappetta, Konrad Urbanek, Liberato Berrino & Antonella De Angelis

Authors
  1. Donato Cappetta
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  2. Konrad Urbanek
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  3. Liberato Berrino
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  4. Antonella De Angelis
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Corresponding author

Correspondence to Antonella De Angelis .

Editor information

Editors and Affiliations

  1. Dept of Drug Sciences, Pharmacology Sect, University of Pavia, Dept of Drug Sciences, Pharmacology Sect, Pavia, Pavia, Italy

    Stefano Govoni

  2. Dept of Brain and Behavioural Sciences, University of Pavia Dept of Brain and Behavioural Sciences, Pavia, Pavia, Italy

    Pierluigi Politi

  3. Department of Molecular Medicine, University of Pavia, Department of Molecular Medicine, Pavia, Pavia, Italy

    Emilio Vanoli

Section Editor information

  1. Dipartimento NeuroFarBa (Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino), Università degli Studi di Firenze, Firenze, Italy

    Raffaele Coppini

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Cappetta, D., Urbanek, K., Berrino, L., De Angelis, A. (2019). Adrenoceptor Blockers. In: Govoni, S., Politi, P., Vanoli, E. (eds) Brain and Heart Dynamics. Springer, Cham. https://doi.org/10.1007/978-3-319-90305-7_49-1

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  • DOI: https://doi.org/10.1007/978-3-319-90305-7_49-1

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  • Print ISBN: 978-3-319-90305-7

  • Online ISBN: 978-3-319-90305-7

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