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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

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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.

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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

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