Sex differences in epidemiology, clinical features, and therapeutical responses are emerging in several movement disorders, even though they are still not widely recognized. Parkinson’s disease (PD) is not an exception: men and women suffering from PD have different levels of disability. Research has been performed using multiple databases and scientific journals; this review summarizes the available evidence on sex differences in PD regarding epidemiology, risk factors, genetics, clinical phenotype, social impact, and therapeutic management. The role of hormones in determining such differences is also briefly discussed. The results confirm the existence of differences between men and women in PD; women have a higher risk of developing disabling motor complications and non-motor fluctuations compared to men, while men have a higher risk of developing cognitive impairment, postural instability, and gait disorders. Improving our knowledge in these differences may result in the implementation of strategies for disease-tailored treatment and management.

Background: Pain, a frequent non-motor symptom in Parkinson’s Disease (PD), significantly impacts on quality of life. Safinamide is a new drug with dopaminergic and non-dopaminergic properties, approved in Europe as adjunct therapy to levodopa for the treatment of fluctuating PD patients. Results from two 24-month, double-blind, placebo-controlled studies demonstrated that safinamide has positive effects on both motor functions and quality of life in PD patients. Objective: To investigate the effects of safinamide on pain management in PD patients with motor fluctuations using pooled data from studies 016 and SETTLE. Methods: This post-hoc analysis evaluated the reduction of concomitant pain treatments and the changes in the scores of the items related to pain of the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39). A path analysis was performed in order to examine direct and indirect associations between safinamide and PDQ-39 pain-related items assessed after 6-months of treatment. Results: The percentage of patients with no pain treatments at the end of the trials was significantly lower in the safinamide group compared to the placebo group. Safinamide 100 mg/day significantly reduced on average the individual use of pain treatments by ≈24% and significantly improved two out of three PDQ-39 pain-related items of the “Bodily discomfort” domain. Path analysis showed that the direct effect of safinamide on pain accounted for about 80% of the total effect. Conclusions: These results suggest that safinamide may have a positive effect on pain, one of the most underestimated non-motor symptoms. Prospective studies are warranted to investigate this potential benefit.

Background: Safinamide is a novel α-aminoamide with dopaminergic and non-dopaminergic properties developed as adjunctive therapy for patients with PD. Results from a 24-month double-blind controlled study suggested that as add-on to levodopa (and ot

Background: Studies 016 and SETTLE showed that safinamide was safe and effective as adjunct therapy in patients with advanced Parkinson’s disease (PD) and motor fluctuations. The addition of safinamide to a stable dose of levodopa alone or with other antiparkinsonian medications significantly increased ON time with no/non-troublesome dyskinesia, decreased OFF time and improved Parkinson’s symptoms. Objective: To evaluate the clinical effects of safinamide 100 mg/day on motor fluctuations and cardinal Parkinson’s symptoms in specific patient subgroups using pooled data from Studies 016 and SETTLE. Methods: Both studies were double blind, placebo-controlled, randomized, phase 3 trials which enrolled patients with mid- to late-stage PD experiencing motor fluctuations while receiving optimized and stable doses of levodopa, alone or with other dopaminergic treatments. The present post-hoc analyses assessed the change from baseline in ON time (with no or non-troublesome dyskinesia) and OFF time in subgroups of patients who were receiving only levodopa at baseline, who were classified as “mild fluctuators” (daily OFF time ≤4 h), and who were receiving concomitant dopaminergic therapy, with or without amantadine, and the effects of safinamide versus placebo on individual cardinal PD symptoms during ON time. Results: Safinamide significantly increased mean ON time (with no or non-troublesome dyskinesia) and reduced mean OFF time when used as first adjunct therapy in levodopa-treated patients and patients with mild motor fluctuations. Mean daily ON time (with no or non-troublesome dyskinesia) and OFF time were favorably changed, compared with placebo, to similar extents regardless of whether patients were receiving concomitant dopamine agonists, catechol-O-methyltransferase inhibitors and amantadine. Additionally, safinamide improved bradykinesia, rigidity, tremor and gait. Conclusions: Safinamide was a safe and effective first adjunct therapy in levodopa-treated patients and improved 4/5 cardinal symptoms of PD while providing benefits to mild and non-mild fluctuators and patients receiving other concomitant dopaminergic therapies.

Background: Mood disorders are very frequent in Parkinson’s Disease (PD), and their effective treatment is still a major unresolved issue: growing evidence suggests that glutamatergic system dysfunction is directly involved. Safinamide is a drug with an innovative mechanism of action, dopaminergic and non-dopaminergic, that includes the reversible inhibition of the monoamine oxidase-B (MAO-B) enzyme and the modulation of excessive glutamate release through the use- and state-dependent blockade of the sodium channels. Objective: To investigate the effects of safinamide on mood over two-year treatment in PD patients with motor fluctuations. Methods: This was a post-hoc analysis of the data from studies 016 and 018. The analysis focused on outcomes related to mood, namely: scores of the “Emotional well-being” domain of the Parkinson’s Disease Questionnaire (PDQ-39), scores of the GRID Hamilton Rating Scale for Depression (GRID-HAMD) and the proportion of patients reporting depression as an adverse event over the entire treatment period. Results: Safinamide, compared to placebo, significantly improved the PDQ-39 “Emotional well-being” domain after6-months ( p = 0.0067) and 2 years ( p = 0.0006), as well as the GRID-HAMD ( p = 0.0408 after 6 months and p = 0.0027 after 2 years). Significantly fewer patients in the safinamide group, compared to placebo, experienced depression as adverse event ( p = 0.0444 after 6 months and p = 0.0057 after 2 years). Conclusion: The favorable effect of safinamide on mood may be explained by the improvement in wearing off and by its modulation of glutamatergic hyperactivity and reversible MAO-B inhibition. Prospective studies are warranted to investigate this potential benefit.

Introduction Chronic pain is an important yet overlooked non-motor symptom of Parkinson’s disease (PD), caused by an imbalance of the dopaminergic and glutamatergic systems. Safinamide has a multimodal mechanism of action, dopaminergic (reversible MAO-B inhibition) and non-dopaminergic (modulation of the abnormal glutamate release), that might be beneficial for both motor and non-motor symptoms. Objectives To investigate the long-term (2-year) efficacy of safinamide on PD chronic pain and to confirm the positive effects observed after 6 months of treatment. Methods This is a post hoc analysis of the data from the 2-year study 018, focused on the reduction of concomitant pain treatments and on the scores of pain-related items of the Parkinson’s disease quality of life questionnaire (PDQ-39). Results Safinamide, compared with placebo, significantly improved the PDQ-39 items 37 (“painful cramps or spasm,” p = 0.0074) and 39 (“unpleasantly hot or cold,” p = 0.0209) and significantly reduced the number of concomitant pain treatments by 26.2% (p = 0.005). A significantly greater proportion of patients in the safinamide group was not using pain drugs after 2 years of treatment (p = 0.0478). Conclusions The positive effects of safinamide on PD chronic pain were maintained in the long term. Further investigations are desirable to confirm their clinical relevance. Funding Zambon SpA.