Switching from Rasagiline to Safinamide as an Add-On Therapy Regimen in Patients with Levodopa: A Literature Review

Abstract

Parkinson’s disease (PD) is a complex disease, and the treatment is focused on the patient’s clinical symptoms. Levodopa continues to be the most effective drug for symptomatic PD treatment. However, chronic levodopa treatment is associated with the development of motor complications in most patients. Add-on therapeutic drugs, such as dopamine agonists and monoamine oxidase B (MAO-B) inhibitors, for example, safinamide and rasagiline, may be a desirable addition to continuously increase the levodopa dose for the optimization of motor control in PD. The scientific literature shows that safinamide significantly alleviated motor fluctuations with no increase in troublesome dyskinesia, thanks to its unique double mechanism, providing further benefits to fluctuating PD patients when compared to a placebo or other drugs. Switching from rasagiline to safinamide has been shown to improve the wearing-off phenomena, which is defined as the recurrent, predictable worsening of symptoms of parkinsonism at the end of the levodopa dose until the next dose reaches a clinical effect. In this situation, safinamide may be helpful for reducing the total daily dose of levodopa, improving the OFF time and ON time without troublesome dyskinesias, and being more effective than other MAO-B inhibitors. In this narrative review, we explore the switch from rasagiline to safinamide in patients with motor complications as a feasible and effective alternative to optimize antiparkinsonian treatment.

Efectividad y seguridad de la safinamida en la Unidad de Trastornos de Movimiento de Toledo

“…Also, as some of the scales used assessed patients’ opinions, there could be a possible placebo effect. The main strength of the study is that it reinforces previous evidence of the benefit of switching from rasagiline to safinamide [ 18 , 39 , 42 ]. One recently published study was conducted with the aim of determining the levodopa equivalent dose.…”

“…As already noted in the aforementioned papers, this remarkable motor improvement could be attributed to safinamide’s non-dopaminergic mechanism of action. A recent review reported that switching from rasagiline to safinamide improved the wearing off phenomenon that occurs as the effect of the levodopa dose comes to an end until the clinical effect of the next one takes place, which could be useful to reduce the total daily dosage of levodopa, while improving the off and on times without troublesome dyskinesias and being more effective than other MAO-B inhibitors [ 42 ].…”

“…In this way, the therapeutic treatment of PD would be approached by restoring the dopaminergic deficit and modulating the existing glutamatergic hyperstimulation, thereby offering a more holistic approach [ 16 ]. Moreover, as recently indicated by Sánchez-Alonso et al, switching from a MAO-B inhibitor to safinamide allows for optimisation of the antiparkinsonian treatment, especially before considering possible advanced or second-line therapies [ 42 ].…”

“…Tal y como ya se apunta en los trabajos anteriormente mencionados, esta remarcable mejoría motora podría atribuirse al mecanismo de acción no dopaminérgico de la safinamida. En una revisión reciente se describió que el cambio de rasagilina a safinamida mejoraba el fenómeno de wearing off que se produce al final de la dosis de levodopa hasta que la siguiente dosis alcance su efecto clínico, lo que podría ser útil para reducir la dosis diaria total de levodopa, mejorando el tiempo off y on sin discinesias molestas, y ser más eficaz que otros IMAO-B [ 42 ].…”

Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment

“…Recently, the European Union (EU) and the US Food and Drug Administration (USFDA) approved safinamide, which is a reversible MAO-B inhibitor to combat mid- to late-stage PD. 19–21…”