nach oben

08.05.2024 | Original Communication

The chronic use of serotonin norepinephrine reuptake inhibitors facilitates dyskinesia priming in early Parkinson’s disease

verfasst von: Massimo Marano, Andrea Pilotto, Alessandro Padovani, Deepak Gupta, Giorgio Vivacqua, Alessandro Magliozzi, Vincenzo Di Lazzaro, Manolo Carta, Mario Meloni

Erschienen in: Journal of Neurology

Einloggen, um Zugang zu erhalten

Abstract

Background

Parkinson’s disease (PD) patients are frequently exposed to antidepressant medications (ADMs). Norepinephrine (NE) and serotonin (5HT) systems have a role in levodopa-induced dyskinesias (LID) pathophysiology.

Methods

We performed a longitudinal analysis on the PPMI cohort including drug-naïve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up.

Results

LID prevalence (according to MDS UPDRS score 4.1 ≥ 1) was 16% (42/251); these patients were more likely women (p = 0.01), had higher motor (p < 0.001) and depression scores (p = 0.01) and lower putaminal DAT binding ratio (p = 0.01). LID were associated with the exposure time to L-DOPA (2.2 ± 1.07 vs 2.6 ± 0.9, p = 0.02) and to the exposure to ADMs, in particular to SNRI (4.8% vs 21.4%, p < 0.001). The latter persisted after correcting for significant covariates (e.g., disease duration, cognitive status, motor impairment, depression, dopaminergic denervation). A similar difference in LID prevalence in PD patients exposed vs non-exposed to SNRI was observed on matched data by the real-world TriNetX repository (22% vs 13%, p < 0.001).

Discussion

This study supports the presence of an effect of SNRI on LID priming in patients with early PD. Independent prospective cohort studies are warranted to further verify such association.

Nur mit Berechtigung zugänglich

Bloem BR, Okun MS, Klein C (2021) Parkinson’s disease. Lancet 397:2284–2303. https://doi.org/10.1016/S0140-6736(21)00218-XCrossRefPubMed

Rodriguez-Blazquez C, Schrag A, Rizos A, Chaudhuri KR, Martinez-Martin P, Weintraub D (2020) Prevalence of non-motor symptoms and non-motor fluctuations in Parkinson’s disease using the MDS-NMS. Mov Disord Clin Pract 8:231–239. https://doi.org/10.1002/mdc3.13122CrossRefPubMedPubMedCentral

Seppi K, Ray Chaudhuri K, Coelho M, Fox SH, Katzenschlager R, Perez Lloret S, Weintraub D, Sampaio C, the collaborators of the Parkinson’s Disease Update on Non-Motor Symptoms Study Group on behalf of the Movement Disorders Society Evidence-Based Medicine Committee (2019) Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov Disord 34:180–198. https://doi.org/10.1002/mds.27602CrossRefPubMedPubMedCentral

Krøigård T, Christensen J, Wermuth L, Ritz B, Lassen CF (2014) The use of antidepressant medication in Parkinson’s disease patients is not affected by the type of antiparkinson medication. J Parkinsons Dis 4:327–330. https://doi.org/10.3233/JPD-140386CrossRefPubMed

Carta M, Carlsson T, Kirik D, Björklund A (2007) Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain 130:1819–1833. https://doi.org/10.1093/brain/awm082CrossRefPubMed

Carta M, Björklund A (2018) The serotonergic system in L-DOPA-induced dyskinesia: pre-clinical evidence and clinical perspective. J Neural Transm (Vienna) 125:1195–1202. https://doi.org/10.1007/s00702-018-1865-5CrossRefPubMed

Cenci MA, Lundblad M (2006) Post- versus presynaptic plasticity in L-DOPA-induced dyskinesia. J Neurochem 99:381–392. https://doi.org/10.1111/j.1471-4159.2006.04124.xCrossRefPubMed

Chase TN (1998) Levodopa therapy: consequences of the nonphysiologic replacement of dopamine. Neurology 50:S17-25. https://doi.org/10.1212/wnl.50.5_suppl_5.s17CrossRefPubMed

Arai A, Tomiyama M, Kannari K, Kimura T, Suzuki C, Watanabe M, Kawarabayashi T, Shen H, Shoji M (2008) Reuptake of L-DOPA-derived extracellular DA in the striatum of a rodent model of Parkinson’s disease via norepinephrine transporter. Synapse 62:632–635. https://doi.org/10.1002/syn.20535CrossRefPubMed

10.

Munoz A, Li Q, Gardoni F, Marcello E, Qin C, Carls-son T et al (2008) Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia. Brain 131:3380–3394CrossRefPubMed

11.

Ostock CY, Lindenbach D, Goldenberg AA, Kampton E, Bishop C (2014) Effects of noradrenergic denervation by anti-DBH-saporin on behavioral responsivity to L-DOPA in the hemi-parkinsonian rat. Behav Brain Res 270:75–85. https://doi.org/10.1016/j.bbr.2014.05.009CrossRefPubMedPubMedCentral

12.

Shin E, Rogers JT, Devoto P, Björklund A, Carta M (2014) Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease. Exp Neurol 257:25–38. https://doi.org/10.1016/j.expneurol.2014.04.011CrossRefPubMed

13.

Mazzucchi S, Frosini D, Ripoli A, Nicoletti V, Linsalata G, Bonuccelli U, Ceravolo R (2015) Serotonergic antidepressant drugs and L-dopa-induced dyskinesias in Parkinson’s disease. Acta Neurol Scand 131:191–195. https://doi.org/10.1111/ane.12314CrossRefPubMed

14.

Bezard E, Tronci E, Pioli EY, Li Q, Porras G, Björklund A, Carta M (2013) Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia. Mov Disord 28:1088–1096. https://doi.org/10.1002/mds.25366CrossRefPubMed

15.

Tronci E, Fidalgo C, Stancampiano R, Carta M (2015) Effect of selective and non-selective serotonin receptor activation on L-DOPA-induced therapeutic efficacy and dyskinesia in parkinsonian rats. Behav Brain Res 292:300–294. https://doi.org/10.1016/j.bbr.2015.06.034CrossRefPubMed

16.

Eskow KL, Gupta V, Alam S, Park JY, Bishop C (2007) The partial 5-HT(1A) agonist buspirone reduces the expression and development of l-DOPA-induced dyskinesia in rats and improves l-DOPA efficacy. Pharmacol Biochem Behav 87:306–314. https://doi.org/10.1016/j.pbb.2007.05.002CrossRefPubMed

17.

Politis M, Wu K, Loane C, Brooks DJ, Kiferle L, Turkheimer FE, Bain P, Molloy S, Piccini P (2014) Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients. J Clin Invest 124:1340–1349. https://doi.org/10.1172/JCI71640CrossRefPubMedPubMedCentral

18.

Fidalgo C, Ko WK, Tronci E, Li Q, Stancampiano R, Chuan Q, Bezard E, Carta M (2015) Effect of serotonin transporter blockade on L-DOPA-induced dyskinesia in animal models of Parkinson’s disease. Neuroscience 298:389–396. https://doi.org/10.1016/j.neuroscience.2015.04.027CrossRefPubMed

19.

Szabo ST, de Montigny C, Blier P (2000) Progressive attenuation of the firing activity of locus coeruleus noradrenergic neurons by sustained administration of selective serotonin reuptake inhibitors. Int J Neuropsychopharmacol 3:1–11CrossRefPubMed

20.

Ostock CY, Bhide N, Goldenberg AA, George JA, Bishop C (2018) Striatal norepinephrine efflux in l-DOPA-induced dyskinesia. Neurochem Int 114:85–98. https://doi.org/10.1016/j.neuint.2018.01.010CrossRefPubMed

21.

Chotibut T, Apple DM, Jefferis R, Salvatore MF (2012) Dopamine transporter loss in 6-OHDA Parkinson’s model is unmet by parallel reduction in dopamine uptake. PLoS ONE 7:e52322. https://doi.org/10.1371/journal.pone.0052322CrossRefPubMedPubMedCentral

22.

Morón JA, Brockington A, Wise RA, Rocha BA, Hope BT (2002) Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J Neurosci 22:389–395. https://doi.org/10.1523/JNEUROSCI.22-02-00389.2002.PMC6758674CrossRefPubMedPubMedCentral

23.

Chotibut T, Fields V, Salvatore MF (2014) Norepinephrine transporter inhibition with desipramine exacerbates L-DOPA-induced dyskinesia: role for synaptic dopamine regulation in denervated nigrostriatal terminals. Mol Pharmacol 86:675–685. https://doi.org/10.1124/mol.114.093302CrossRefPubMed

24.

Fulceri F, Biagioni F, Ferrucci M, Lazzeri G, Bartalucci A, Galli V, Ruggieri S, Paparelli A, Fornai F (2007) Abnormal involuntary movements (AIMs) following pulsatile dopaminergic stimulation: severe deterioration and morphological correlates following the loss of locus coeruleus neurons. Brain Res 1135:219–229. https://doi.org/10.1016/j.brainres.2006.12.030CrossRefPubMed

25.

Czubak A, Nowakowska E, Golembiowska K, Kus K, Burda K, Metelska J (2010) Effect of venlafaxine and nicotine on the level of neurotransmitters and their metabolites in rat brains. J Physiol Pharmacol 61:339–346PubMed

26.

Barnum CJ, Bhide N, Lindenbach D, Surrena MA, Goldenberg AA, Tignor S, Klioueva A, Walters H, Bishop C (2012) Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and β-adrenergic receptor antagonists in hemiparkinsonian rats. Pharmacol Biochem Behav 100:607–615. https://doi.org/10.1016/j.pbb.2011.09.009CrossRefPubMed

27.

Holmberg M, Scheinin M, Kurose H, Miettinen R (1999) Adrenergic alpha2C-receptors reside in rat striatal GABAergic projection neurons: comparison of radioligand binding and immunohistochemistry. Neuroscience 93:1323–1333. https://doi.org/10.1016/s0306-4522(99)00260-2CrossRefPubMed

28.

Hara M, Fukui R, Hieda E, Kuroiwa M, Bateup HS, Kano T, Greengard P, Nishi A (2010) Role of adrenoceptors in the regulation of dopamine/DARPP-32 signaling in neostriatal neurons. J Neurochem 113:1046–1059. https://doi.org/10.1111/j.1471-4159.2010.06668.xCrossRefPubMedPubMedCentral

29.

Miguelez C, Aristieta A, Cenci MA, Ugedo L (2011) The locus coeruleus is directly implicated in L-DOPA-induced dyskinesia in parkinsonian rats: an electrophysiological and behavioural study. PLoS ONE 6(9):e24679. https://doi.org/10.1371/journal.pone.0024679CrossRefPubMedPubMedCentral

30.

Eusebi P, Romoli M, Paoletti FP, Tambasco N, Calabresi P, Parnetti L (2018) Risk factors of levodopa-induced dyskinesia in Parkinson’s disease: results from the PPMI cohort. NPJ Parkinsons Dis 4:33. https://doi.org/10.1038/s41531-018-0069-xCrossRefPubMedPubMedCentral

Titel: The chronic use of serotonin norepinephrine reuptake inhibitors facilitates dyskinesia priming in early Parkinson’s disease
verfasst von: Massimo Marano
Andrea Pilotto
Alessandro Padovani
Deepak Gupta
Giorgio Vivacqua
Alessandro Magliozzi
Vincenzo Di Lazzaro
Manolo Carta
Mario Meloni
Publikationsdatum: 08.05.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-024-12400-6

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Schwindelursache: Massagepistole lässt Otholiten tanzen

14.05.2024 Benigner Lagerungsschwindel Nachrichten

Wenn jüngere Menschen über ständig rezidivierenden Lagerungsschwindel klagen, könnte eine Massagepistole der Auslöser sein. In JAMA Otolaryngology warnt ein Team vor der Anwendung hochpotenter Geräte im Bereich des Nackens.

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen