Objective: To assess the role of different factors in the antidepressant effect of safinamide in Parkinson’s disease (PD)

Background: SADNESS-PD was a real-life, multicenter, retrospective study which assessed the effect of safinamide on depression and motor state in PD. Its conclusions were that safinamide could improve depression in PD. This antidepressant effect of safinamide was related to its dual mechanism of action as a glutamatergic modulator and dopaminergic stimulator. However other indirect mechanisms of action could be involved such as improvement in motor functions, motor complications or in other nonmotor symptoms as pain, since safinamide has also been postulated to improve pain in PD

Method: Linear multivariate regression model (LMRM), comparing improvement in Hamilton depression rating scale (HAMD-17) at 3 months of follow-up respecting to baseline with variations in UPDRS III total score (motor functions), UPDRS IV total score (motor complications) and the number of patients with pain according to the item 17 of the UPDRS II. P values < 0.05 were considered statistically significant. Data were shown as means(standard deviations) or relative frequencies

Results: n=82(safinamide 50mg=26,8%, 100mg=73,2%). Female=54.9 %. Age(years)=68.33(11.41). Disease duration(years)=8.67(8.55). Baseline data: HAMD-17=19.49(4.03), UPDRS I=4.56(1.82), II=13.59(6.67), III=22.91(8.68), IV=3.51(2.83), patients with pain=12.2 %. Variations at 3 months of follow-up: HAMD-17=-7.27(5.48), UPDRS III=-4.03(8.95), UPDRS IV=-0.8(2.53), pain=-30%. LMRM(95% confidence Interval for beta): UPDRS III=0.253 to 0.576(p<0.001), UPDRS IV=-0.402 to 1.013(p=0.39), pain=0.009 to 6.915 (p=0.04). R-Squared=36.7 %. Simple linear regression between variations in UPDRS III vs. pain was not significant, showing that both variables were independent (beta=-0.183, p=0.09)

Conclusion: Our results showed that the antidepressant effect of safinamide in PD is associated with two indirect and independent factors: the improvement of motor functions (the most important) and the improvement of pain. However, according to the R-squared, both of them only explain the 36.7 % of variation in HAMD-17. It suggests that the main factor related to the antidepressant effect of safinamide could not be an indirect factor and that the direct effects previously postulated could have a relevant role

References: * Peña E, Borrué C, Mata M, Martínez Castrillo et al: Impact of SAfinamide on Depressive Symptoms in Parkinson’s Disease Patients (SADness-PD Study): A Multicenter Retrospective Study. Brain Sci. 2021; 11: 232
* Grigoriou S, Martínez-Martín P, Chaudhuri KR, Rukavina K et al: Effects of safinamide on pain in patients with fluctuating Parkinson’s disease. Brain Behav. 2021; 11: e2336

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MDS Abstracts - https://www.mdsabstracts.org/abstract/factors-related-to-the-antidepressant-effect-of-safinamide-in-parkinsons-disease-a-post-hoc-analysis-of-sadness-pd-study/