Serotonin Syndrome and Drug Interactions, Hypertensive Complications, and, Adverse Effects of Monoamine Oxidase Inhibitors in Patients with Parkinson’s Disease

doi:10.1017/9781009039291.022

Chapter 21 - Serotonin Syndrome and Drug Interactions, Hypertensive Complications, and, Adverse Effects of Monoamine Oxidase Inhibitors in Patients with Parkinson’s Disease

Published online by Cambridge University Press: 05 March 2022

Eoin Mulroy and

Kailash P. Bhatia

Edited by

Néstor Gálvez-Jiménez ,

Amos D. Korczyn and

Ramón Lugo-Sanchez

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Néstor Gálvez-Jiménez: Affiliation:
Florida International University
Amos D. Korczyn: Affiliation:
Tel-Aviv University
Ramón Lugo-Sanchez: Affiliation:
Cleveland Clinic

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Summary

Monoamine oxidase (MAO), located in the outer mitochondrial membrane, is a critical enzyme in the metabolism of a number of neurotransmitters. Two isoforms of the enzyme exist, MAO-A and MAO-B [1]. These differ both in their tissue distribution and substrate selectivity. MAO-A is predominantly located in the periphery (including the gut) and preferentially catalyses the oxidation of 5-hydroxytyptamine (5-HT, serotonin) and norepinephrine [1]. MAO-B selectively metabolizes beta-phenylethylamine, while tyramine and dopamine are substrates for both types [1]. MAO inhibition, either non-specific or selective, increases the synaptic concentrations of the usually metabolized neurochemicals, providing symptomatic benefit in a variety of neurological and psychiatric disorders.

Type: Chapter
Information: Non-motor Parkinson's Disease , pp. 241 - 251

DOI: https://doi.org/10.1017/9781009039291.022 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2022

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References

Kalgutkar, AS, Dalvie, DK, Castagnoli, N Jr, Taylor, TJ. Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: SAR studies on MAO substrates and inhibitors. Chem Res Toxicol 2001; 14(9): 1139–1162.Google Scholar

Riederer, P, Laux, G. MAO-inhibitors in Parkinson’s Disease. Exp Neurobiol 2011; 20(1): 1–17.CrossRef Google Scholar PubMed

Johnston, JP. Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 1968; 17(7): 1285–1297.CrossRef Google Scholar PubMed

Robakis, D, Fahn, S. Defining the role of the monoamine oxidase-B inhibitors for Parkinson’s disease. CNS Drugs 2015; 29(6): 433–441.Google Scholar

Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1993; 328(3): 176–183.CrossRef Google Scholar

Lees, AJ. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson’s disease. Parkinson’s Disease Research Group of the United Kingdom. Br Med J. 1995; 311(7020): 1602–1607.Google Scholar

Myllylä, VV, Sotaniemi, KA, Hakulinen, P, Mäki-Ikola, O, Heinonen, EH. Selegiline as the primary treatment of Parkinson’s disease–a long-term double-blind study. Acta Neurol Scand 1997; 95(4): 211–218.Google Scholar

Nayak, L, Henchcliffe, C. Rasagiline in treatment of Parkinson’s disease. Neuropsychiatr Dis Treat 2008; 4(1): 23–32.Google Scholar

Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002; 59(12): 1937–1943.Google Scholar

Olanow, CW, Rascol, O, Hauser, R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med 2009; 361(13): 1268–1278.CrossRef Google Scholar PubMed

Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 2005; 62: 241–248.Google Scholar

Rascol, O, Brooks, DJ, Melamed, E, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005; 365: 947–954.CrossRef Google Scholar PubMed

Bette, S, Shpiner, DS, Singer, C, Moore, H. Safinamide in the management of patients with Parkinson’s disease not stabilized on levodopa: a review of the current clinical evidence. Ther Clin Risk Manag 2018; 14: 1737–1745.Google Scholar

Shulman, KI, Fischer, HD, Herrmann, N, et al. Current prescription patterns and safety profile of irreversible monoamine oxidase inhibitors: a population-based cohort study of older adults. J Clin Psychiatry. 2009; 70(12): 1681–1686.Google Scholar

Karlsen, K, Larsen, JP, Tandberg, E, Jørgensen, K. Fatigue in patients with Parkinson’s disease. Mov Disord 1999; 14: 237–241.Google Scholar

Clarke, A, Brewer, F, Johnson, ES, et al. A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition. J Neural Transm 2003; 110(11): 1241–1255.Google Scholar

Sandoval-Rincón, M, Sáenz-Farret, M, Miguel-Puga, A, Micheli, F, Arias-Carrión, O. Rational pharmacological approaches for cognitive dysfunction and depression in Parkinson’s disease. Front Neurol 2015; 6: 71.Google Scholar PubMed

Schapira, AH. Monoamine oxidase B inhibitors for the treatment of Parkinson’s disease: a review of symptomatic and potential disease-modifying effects. CNS Drugs 2011; 25(12): 1061–1071.CrossRef Google Scholar PubMed

Boll, MC, Alcaraz-Zubeldia, M, Rios, C. Medical management of Parkinson’s disease: focus on neuroprotection. Curr Neuropharmacol 2011; 9(2): 350–359.Google Scholar

Tatton, W, Chalmers-Redman, R, Tatton, N. Neuroprotection by deprenyl and other propargylamines: glyceraldehyde-3-phosphate dehydrogenase rather than monoamine oxidase B. J Neural Transm 2003; 110(5): 509–515.Google Scholar

Wu, RM, Chen, RC, Chiueh, CC. Effect of MAO-B inhibitors on MPP? toxicity in vivo. Ann N Y Acad Sci 2000; 899: 255–261.Google Scholar

Oates, JA, Sjoerdsma, A. Neurologic effects of tryptophan in patients receiving a monoamine oxidase inhibitor. Neurology 1960; 10: 1076–1078.Google Scholar

Moss, MJ, Hendrickson, RG. Toxicology Investigators Consortium (ToxIC). Serotonin toxicity: associated agents and clinical characteristics. J Clin Psychopharmacol 2019; 39(6): 628–633.Google Scholar

Scotton, WJ, Hill, LJ, Williams, AC, Barnes, NM. Serotonin syndrome: pathophysiology, clinical features, management, and potential future directions. Int J Tryptophan Res 2019; 12: 1178646919873925.Google Scholar

Reijnders, JS, Ehrt, U, Weber, WE, Aarsland, D, Leentjens, AF. A systematic review of prevalence studies of depression in Parkinson’s disease. Mov Disord 2008; 23(2): 183–189; quiz 313.Google Scholar

Aarsland, D, Påhlhagen, S, Ballard, CG, Ehrt, U, Svenningsson, P. Depression in Parkinson disease–epidemiology, mechanisms and management. Nat Rev Neurol 2011; 8(1): 35–47.CrossRef Google Scholar PubMed

Starkstein, SE, Mayberg, HS, Leiguarda, R, et al. A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1992; 55: 377–382.CrossRef Google Scholar PubMed

Müller, B, Assmus, J, Herlofson, K, Larsen, JP, Tysnes, OB. Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson’s disease. Parkinsonism Relat Disord 2013; 19(11): 1027–1032.Google Scholar

Hughes, TA, Ross, HF, Mindham, RH, Spokes, EG. Mortality in Parkinson’s disease and its association with dementia and depression. Acta Neurol Scand 2004; 110: 118–123.CrossRef Google Scholar PubMed

Boyer, EW, Shannon, M. The serotonin syndrome. N Engl J Med 2005; 352(11): 1112–1120.Google Scholar

Sternbach, H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705–713.Google Scholar PubMed

Radomski, JW, Dursun, SM, Reveley, MA, Kutcher, SP. An exploratory approach to the serotonin syndrome: an update of clinical phenomenology and revised diagnostic criteria. Med Hypotheses 2000; 55(3): 218–224.Google Scholar

Dunkley, EJ, Isbister, GK, Sibbritt, D, Dawson, AH, Whyte, IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003; 96(9): 635–642.Google Scholar

Youdim, MB, Gross, A, Finberg, JP. Rasagiline [N-propargyl-1 R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol 2001; 132(2): 500–506.Google Scholar

Richard, IH, Kurlan, R, Tanner, C, et al. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson’s disease. Parkinson Study Group. Neurology 1997; 48(4): 1070–1077.Google Scholar

Panisset, M, Chen, JJ, Rhyee, SH, Conner, J, Mathena, J. STACCATO study investigators. Serotonin toxicity association with concomitant antidepressants and rasagiline treatment: retrospective study (STACCATO). Pharmacotherapy 2014; 34(12): 1250–1258.Google Scholar

Smith, KM, Eyal, E, Weintraub, D, ADAGIO Investigators. Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability. JAMA Neurol 2015; 72(1): 88–95.Google Scholar

Hébant, B, Guillaume, M, Desbordes, M, et al. Combination of paroxetine and rasagiline induces serotonin syndrome in a parkinsonian patient. Rev Neurol 2016; 172(12): 788–789.CrossRef Google Scholar

Sanyal, D, Chakraborty, S, Bhattacharyya, R. An interesting case of serotonin syndrome precipitated by escitalopram. Indian J Pharmacol 2010; 42(6): 418–419.Google Scholar

Suphanklang, J, Santimaleeworagun, W, Supasyndh, O. Combination of escitalopram and rasagiline induced serotonin syndrome: a case report and review literature. J Med Assoc Thai 2015; 98(12): 1254–1257.Google Scholar

Bilbao Garay, J, Mesa Plaza, N, Castilla Castellano, V, Dhimes Tejada, P. Serotonin syndrome: report of a fatal case and review of the literature. Rev Clin Esp 2002; 202(4): 209–211.Google Scholar

Duval, F, Flabeau, O, Razafimahefa, J, Spampinato, U, Tison, F. Encephalopathy associated with rasagiline and sertraline in Parkinson’s disease: possible serotonin syndrome. Mov Disord 2013; 28(10): 1464.Google Scholar

Hinds, NP, Hillier, CE, Wiles, CM. Possible serotonin syndrome arising from an interaction between nortriptyline and selegiline in a lady with parkinsonism. J Neurol 2000; 247(10): 811.Google Scholar

Hisham, M, Sivakumar, MN, Nandakumar, V, Lakshmikanthcharan, S. Linezolid and rasagiline – a culprit for serotonin syndrome. Indian J Pharmacol 2016; 48(1): 91–92.Google Scholar

Fernandes, C, Reddy, P, Kessel, B. Rasagiline-induced serotonin syndrome. Mov Disord 2011; 26(4): 766–767.Google Scholar

Francescangeli, J, Karamchandani, K, Powell, M, Bonavia, A. The serotonin syndrome: from molecular mechanisms to clinical practice. Int J Mol Sci 2019; 20(9): E2288.CrossRef Google Scholar PubMed

Blackwell, B, Mabbitt, LA. Tyramine in cheese related to hypertensive crises after monoamine oxidase inhibition. Lancet 1965; 1: 938–940.Google Scholar

Ito, D, Amano, T, Sato, H, Fukuuchi, Y. Paroxysmal hypertensive crises induced by selegiline in a patient with Parkinson’s disease. J Neurol 2001; 248(6): 533–534.Google Scholar

Montastruc, JL, Chamontin, B, Senard, JM, et al. Pseudophaeochromocytoma in parkinsonian patients treated with fluoxetine plus selegiline. Lancet 1993; 341(8844): 555.Google Scholar

Rose, LM, Ohlinger, MJ, Mauro, VF. A hypertensive reaction induced by concurrent use of selegiline and dopamine. Ann Pharmacother 2000; 34(9): 1020–1024.CrossRef Google Scholar PubMed

Cockhill, LA, Remick, RA. Blood pressure effects of monoamine oxidase inhibitors–the highs and lows. Can J Psychiatry 1987; 32(9): 803–808.Google Scholar

Pursiainen, V, Korpelainen, TJ, Haapaniemi, HT, et al. Selegiline and blood pressure in patients with Parkinson’s disease. Acta Neurol Scand 2007; 115: 104–108.Google Scholar

Shoulson, I, Oakes, D, Fahn, S, et al. Impact of sustained deprenyl (selegiline) in levodopa-treated PD: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidant therapy of parkinsonism trial. Ann Neurol 2002; 51: 604–612.CrossRef Google Scholar PubMed

Abassi, ZA, Binah, O, Youdim, MB. Cardiovascular activity of rasagiline, a selective and potent inhibitor of mitochondrial monoamine oxidase B: comparison with selegiline. Br J Pharmacol 2004; 143(3): 371–378.Google Scholar

Minguez-Minguez, S, Solis-Garcia, del Pozo J, Jordan, J. Rasagiline in Parkinson’s disease: a review based on meta-analysis of clinical data. Pharmacol Res 2013; 74: 78–86.Google Scholar

Dezsi, L, Vecsei, L. Monoamine oxidase B inhibitors in Parkinson’s disease. CNS Neurol Disord Drug Targets 2017; 16(4): 425–439.Google Scholar

Montastruc, JL, Chaumerliac, C, Desboeuf, K, et al. Adverse drug reactions to selegiline: a review of the French pharmacovigilance database. Clin Neuropharmacol 2000; 23(5): 271–275.Google Scholar

Kamakura, K, Mochizuki, H, Kaida, K, et al. Therapeutic factors causing hallucination in Parkinson’s disease patients, especially those given selegiline. Parkinsonism Relat Disord 2004; 10(4): 235–242.Google Scholar

Centi, J, Freeman, R, Gibbons, CH, et al. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology 2017; 88(1): 17–24.CrossRef Google Scholar PubMed