Monoamine oxidase-B (MAO-B) inhibitors are commonly used for the symptomatic treatment of Parkinson's disease (PD). MAO-B inhibitor monotherapy has been shown to be effective and safe for the treatment of early-stage PD, while MAO-B inhibitors as adjuvant drugs have been widely applied for the treatment of the advanced stages of the illness. MAO-B inhibitors can effectively improve patients' motor and non-motor symptoms, reduce "OFF" time, and may potentially prevent/delay disease progression. In this review, we discuss the effects of MAO-B inhibitors on motor and non-motor symptoms in PD patients, their mechanism of action, and the future development of MAO-B inhibitor therapy. 

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Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson’s Disease: Past, Present, and Future

Some studies observed a benefit of Parkinson's disease (PD) patients after treatment with safinamide in some non-motor symptoms (NMSs). The aim of this study was to analyze the effectiveness of safinamide on NMS burden in PD. SAFINONMOTOR (an open-label study of the effectiveness of safinamide on non-motor symptoms in Parkinson's disease patients) is a prospective open-label single-arm study conducted in five centers from Spain. The primary efficacy outcome was the change from baseline (V1) to the end of the observational period (6 months) (V4) in the non-motor symptoms scale (NMSS) total score. Between May/2019 and February/2020 50 patients were included (age 68.5 ± 9.12 years; 58% females; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The NMSS total score was reduced by 38.5% (from 97.5 ± 43.7 in V1 to 59.9 ± 35.5 in V4; p < 0.0001). By domains, improvement was observed in sleep/fatigue (-35.8%; p = 0.002), mood/apathy (-57.9%; p < 0.0001), attention/memory (-23.9%; p = 0.026), gastrointestinal symptoms (-33%; p = 0.010), urinary symptoms (-28.3%; p = 0.003), and pain/miscellaneous (-43%; p < 0.0001). Quality of life (QoL) also improved with a 29.4% reduction in the PDQ-39SI (from 30.1 ± 17.6 in V1 to 21.2 ± 13.5 in V4; p < 0.0001). A total of 21 adverse events in 16 patients (32%) were reported, 5 of which were severe (not related to safinamide). Dyskinesias and nausea were the most frequent (6%). Safinamide is well tolerated and improves NMS burden and QoL in PD patients with severe or very severe NMS burden at 6 months.

https://www.mdpi.com/2076-3425/11/3/316/pdf

Safinamide Improves Non-Motor Symptoms Burden in Parkinson's Disease: An Open-Label Prospective Study.

The role of glutamatergic neurotransmission in the motor and non-motor symptoms in Parkinson's disease: Clinical cases and a review of the literature.

Background: We aimed to assess the effects of safinamide on depression, motor symptoms, and the serotonin syndrome related to its co-administration with antidepressants in patients with Parkinson’s disease (PD). Methods: We retrospectively analyzed the data of patients at 1 and 3 months of follow-up compared to baseline. Results: n = 82 (safinamide 50 mg = 22, 100 mg = 60, with antidepressants = 44). First, we found improvement in depression (Hamilton Depression Rating Scale: −6 ± 5.10 at 1 month and −7.27 ± 5.10 at 3 months, p < 0.0001; Patient Global Impression of Improvement Scale: 60.3% and 69.5% of patients at 1 and 3 months reported some improvement). Second, safinamide improved the daily life activities and motor symptoms/motor complications (Unified Parkinson’s Disease Rating Scale (UPDRS-II): −2.51 ± 6.30 and −2.47 ± 6.11 at 1 and 3 months, p < 0.0001; III: −3.58 ± 8.68 and −4.03 ± 8.95 at 1 and 3 months, p < 0.0001; IV: −0.61 ± 2.61 and −0.8 ± 2.53 at 1 and 3 months, p < 0.0001). Third, 7.31% and 8.53% of patients developed non-severe adverse events related to safinamide at 1 and 3 months. Serotonin syndrome was not observed in the patients treated with antidepressants; some isolated serotonin syndrome symptoms were reported. Conclusions: Safinamide could be useful for treating depression in PD; it was effective for motor symptoms and motor complications and safe even when co-administered with antidepressants.

Impact of SAfinamide on Depressive Symptoms in Parkinson's Disease Patients (SADness-PD Study): A Multicenter Retrospective Study

Introduction Parkinson's therapeutic interventions are only symptomatic. An optimal treatment should therefore address the largest number of motor and non-motor symptoms, to manage patients at best. Safinamide is one of the most recent approved drugs for fluctuating patients, in add-on to levodopa, that remains the gold standard treatment. It has a unique mechanism of action, both dopaminergic (as MAO-B inhibitor) and glutamatergic (through Na+ channel blockade). Results from Phase III trials, post-hoc analyses and real-life experiences suggest a beneficial effect on motor (such as tremor, bradykinesia, rigidity and gait) and non-motor (pain, mood, sleep) symptoms. Areas covered Here, the authors discuss clinical efficacy and safety of safinamide, identifying the patients' profiles that could benefit most. A search in PubMed was performed in September 2020, with no time limits. Publications' abstracts were reviewed. Conclusion Safinamide is peculiar due to its double mechanism of action. Its benefits in improving motor functions and fluctuations, and some non-motor symptoms, could have a valuable impact on patients' quality of life (QoL), together with its safety profile.

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The Current Evidence for the Use of Safinamide for the Treatment of Parkinson's Disease

Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized, double-blind, placebo-controlled, phase II/III study.

Long-term safety and efficacy of safinamide as add-on therapy in levodopa-treated Japanese patients with Parkinson's disease with wearing-off: Results of an open-label study.

Asenapine is used to treat schizophrenia and bipolar I disorder. 1 Recent meta-analyses demonstrated that asenapine is well-tolerated and reduces overall symptoms in people with acute bipolar mania and schizophrenia. 2,3 Recently, a 52-week open-label, phase III extension study (NCT01244828 and JapicCTI-132,325) of asenapine (5 or 10 mg BID) add-on treatment for schizophrenia adults receiving antipsychotics was conducted. 4 The study included participants with residual-type schizophrenia (RTS), 5 those who received antipsychotics in a polypharmacy setting, those who received high-dose antipsychotics, those with treatment-resistant schizophrenia, and those with geriatric schizophrenia. A total of 157 participants with a mean Positive and Negative Syndrome Scale 6 total scores (PANSS-T) of 90.20 (cid:1) 18.50 at a baseline were recruited. 4 The change PANSS-T from baseline to endpoint was (cid:3) 5.48 (cid:1) 13.34. 4 Response rate was 18.3%. 4 One of the ﬁ ve patient ’ s death during the trial might be related to asenapine use (the detailed information: Supplementary text). 4 Among the participants, 138 (87.9%) reported any adverse events. 4 The number of individuals who discontinued due to adverse events was 37 (23.6% 4 ). 4 Nasopharyngitis was the most common adverse event, occurring in 21.0% of participants, followed by schizophrenia (13.4%), somnolence (12.7%), weight gain (12.7%), and oral hypoaesthesia (10.8%). The authors concluded that asenapine add-on treatment was effective and safe for different types of schizophrenia patients. 4 However, this study did not consider the disease severity at baseline (i.e. PANSS-T) or age, resulting in heterogeneous characteristics and an unclear conclusion to

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/pcn.13540

Yuji Sasagawa

Papers

Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized, double-blind, placebo-controlled, phase II/III study.

Long-term safety and efficacy of safinamide as add-on therapy in levodopa-treated Japanese patients with Parkinson's disease with wearing-off: Results of an open-label study.

Asenapine add‐on treatment for schizophrenia adults who received antipsychotics: A 52‐week, open‐label study