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CC BY 4.0 · Arq Neuropsiquiatr 2023; 81(05): 460-468
DOI: 10.1055/s-0043-1768668
Original Article

Doxycycline to treat levodopa-induced dyskinesias in Parkinson's disease: a preliminary study

Doxiciclina no tratamento das discinesias induzidas pela doença de Parkinson: um estudo preliminar
Bruno Lopes Santos-Lobato 
1   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brazil.
2   Universidade Federal do Pará, Faculdade de Medicina, Laboratório de Neuropatologia Experimental, Belém PA, Brazil.
,
Manuelina Mariana Capellari Macruz Brito 
1   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brazil.
,
Ângela Vieira Pimentel 
1   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brazil.
,
Rômulo Torres Oliveira Cavalcanti 
1   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brazil.
,
Elaine Del-Bel 
3   Universidade de São Paulo, Faculdade de Odontologia de Ribeirão Preto, Ribeirão Preto SP, Brazil.
,
Vitor Tumas 
1   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brazil.
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Abstract

Background Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinson's disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties.

Objective To evaluate the efficacy and safety of doxycycline in patients with PD and LID.

Methods This was an open-label, uncontrolled, single-arm, single-center, phase 2 proof-of-concept study in patients with PD with functional impact of dyskinesia, which used levodopa three times daily, in a movement disorders clinic in Brazil. Participants were treated with doxycycline 200 mg/day for 12 weeks, with evaluations at baseline, week 4, and week 12 of treatment. The primary outcome measure was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) total score at week 12, evaluated by two blinded raters. Key secondary outcomes measures were OFF time and ON time with troublesome dyskinesia in the PD home diary.

Results Eight patients with PD were treated and evaluated. Doxycycline 200 mg/day reduced the UDysRS total score at week 12, compared with baseline (Friedman χ2 = 9.6; p = 0.008). Further, doxycycline reduced the ON time with troublesome dyskinesia (Friedman χ2 = 10.8; p = 0.004) without worsening parkinsonism. There were no severe adverse events, and dyspepsia was the commonest event.

Conclusion In this preliminary, open-label and uncontrolled trial, doxycycline was effective in reducing LID and safe after a 12-week treatment. Further well-designed placebo-controlled clinical trials with a longer duration and a larger number of participants are needed.

Clinical trial registration https://ensaiosclinicos.gov.br, identifier: RBR-1047fwbf

Resumo

Antecedentes A discinesia induzida por levodopa (DIL) é uma complicação motora comum da terapia com levodopa em pacientes com doença de Parkinson (DP). A doxiciclina é uma tetraciclina amplamente usada e barata, com propriedade anti-inflamatória.

Objetivo Avaliar a eficácia e segurança da doxiciclina em pacientes com DP e DIL.

Métodos Este foi um estudo aberto, não-controlado, de braço único, monocêntrico, fase 2 e de prova de conceito, em pacientes com DP e impacto funcional das discinesias, que usavam levodopa três vezes ao dia, em um ambulatório de distúrbios de movimento no Brasil. Os participantes foram tratados com doxiciclina 200 mg/dia por 12 semanas, com avaliações na base, na semana 4 e na semana 12 do tratamento. A medida de desfecho primário foi a mudança no escore total da Unified Dyskinesia Rating Scale (UDysRS) da base à semana 12, avaliada por dois avaliadores cegos. As medidas-chave de desfecho secundário fora o tempo em OFF e tempo em ON com discinesia problemática.

Resultados Oito pacientes com DP foram tratados e avaliados. A doxiciclina 200 mg/dia reduziu o escore total da UDysRS na semana 12, comparado com a avaliação inicial (χ2 de Friedman = 9.6; p = 0.008). Além disso, a doxiciclina reduziu o tempo em ON com discinesia problemática (χ2 de Friedman = 10.8; p = 0.004) sem piorar o parkinsonismo. Não houve eventos adversos graves, e dispepsia foi o evento mais comum.

Conclusão No presente estudo preliminar, aberto e não-controlado, a doxiciclina foi eficaz em reduzir as DIL e segura após tratamento por 12 semanas. Estudos clínicos bem-desenhados e placebo-controlados adicionais, com duração mais longa e maior número de participantes, são necessários.

Keywords

Parkinson Disease - Dyskinesias - Doxycycline - Neuroinflammatory Diseases

Palavras-chave

Doença de Parkinson - Discinesias - Doxiciclina - Doenças Neuroinflamatórias

Authors' Contributions

BLS-L, MMCMB: these authors have contributed equally to the present work and share first authorship; BLS-L, EDB, VT: conceptualization; BLS-L, MMCMB, AVP, VT: methodology; BLS-L, MMCMB, AVP, RTOC, VT: cinical data collection; BLS-L, MMCMB, RTOC: data analysis; BLS-L: paper writing. All authors contributed to the study conception and design and paper revising.




Publikationsverlauf

Eingereicht: 01. Oktober 2022

Angenommen: 15. Januar 2023

Artikel online veröffentlicht:
31. Mai 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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