Impact of Safinamide on Patient-Reported Outcomes in Parkinson’s Disease

Abstract

Introduction Parkinson’s disease (PD) is a chronic and progressive neurodegenerative condition due to the degeneration of nigral dopaminergic cells. Both motor and non-motor symptoms (NMS) of PD produce a marked impairment in PD patients’ quality of life (QoL), but contrary to motor features, NMS do not improve with dopamine replacement. Novel therapeutic interventions for PD have successfully controlled most motor manifestations of PD, but the management of NMS is still challenging. Since NMS have a negative impact on the QoL of PD patients, researchers are currently looking for drugs that can modulate the activity of neurotransmitter systems other than dopamine in the hope that can alleviate NMS in PD. Among the recently approved drugs for patients experiencing fluctuations in motor symptoms, safinamide stands out as an effective add-on therapy to levodopa. Safinamide is a monoamine oxidase type-B inhibitor (MAOB-I), with proven efficacy in reducing motor fluctuations. Its distinctive mechanism of action impacts dopaminergic pathways via MAOB inhibition and glutamatergic pathways by blocking sodium and calcium channels. Findings from Phase III clinical trials, meta-analysis, post-hoc analysis, and real-life experiences indicate that safinamide benefits motor symptoms such as tremor, bradykinesia, rigidity, and gait. Additionally, it shows promise for improving NMS like fatigue, pain, mood, and sleep disturbances in patients with PD. Areas Covered In this article, the authors explore the impact of safinamide on patient-reported outcomes in PD. A thorough search was conducted on PubMed focusing on studies published between 2018 and 2023 in English. The inclusion criteria encompassed clinical trials, randomized controlled trials, systematic reviews, meta-analyses, and reviews. The search strategy revolved around the implementation of MeSH terms related to safinamide and its impact on the quality of life in PD. Conclusion Our data strongly support the improving effect on QoL, reducing the disabling NMS reported in patients with PD.

Terapéutica para el bloqueo de la marcha en pacientes con Parkinson

“…Dicho ejercicio aumenta la liberación de dopamina, afecta la sinaptogénesis, incrementa el flujo sanguíneo cerebral regional y eleva los niveles de neurotrofinas cerebrales endógenas (por ejemplo, BDNF, GDNF), lo que sugiere que puede mitigar la pérdida de dopamina estriatal. Asimismo, regula el transportador de dopamina estriatal y el transportador vesicular de monoamina (Espinoza-Vinces et al, 2023).…”

“…En resumen, estos resultados indican que los beneficios del entrenamiento de resistencia son más notables cuando se enfocan en limitaciones funcionales específicas que requieren la generación de fuerza muscular en intervalos de tiempo limitados, como en las transiciones de sentarse a pararse, subir escaleras o realizar tos (Espinoza-Vinces et al, 2023).…”

“…La recomendación para someterse a la cirugía de ECP se realiza en pacientes con EP que experimentan complicaciones motoras que no responden adecuadamente al tratamiento médico. Es importante destacar que, a pesar de que el paciente con EP aún responde bien a la carbidopa/levodopa, se enfrenta a complicaciones derivadas de una discinesia excesiva (Espinoza-Vinces et al, 2023).…”

Role of the Night-Time Systemic Processes and the Astrocyte Tryptophan-Melatonin Pathway in the Regulation of α-Synuclein and Wider Parkinson’s Disease Pathophysiology

“…The importance of the tryptophan-melatonin pathway, perhaps especially in astrocytes, in the pathophysiology of PD is given some support by wider data. A number of factors indicate suppressed melatonin production in the SNpc, including 1) decreased melatonin receptors in SNpc dopamine neurons, which may be indicative of suppressed melatonin, given that melatonin induces its own receptors [12]; 2) suppressed tryptophan levels and increased kynurenine pathway products in PD [1]; and 3) the efficacy of monoamine oxidase inhibitors on PD motor symptom treatment [79]. Importantly, decreased levels of different 14-3-3 isoforms significantly potentiate SNpc neuron loss with 14-3-3 isoforms attenuating α-synuclein aggregation and toxicity [80].…”