Specialist in Neurology
Honorary Clinical Associate Professor,
Department of Medicine & Therapeutics,
Chinese University of Hong Kong (CUHK)
A 72-year-old man, previously diagnosed with Parkinson’s disease (PD) 10 years ago, presented with persistent end-of-dose resting tremor despite regular follow-up at a public hospital. He was partially dependent in his activities of daily living (ADL) and consulted Dr. Fung’s clinic due to insomnia and ongoing PD-related symptoms.
On examination, the patient exhibited a mild resting tremor in the right hand, rigidity and bradykinesia on the right side, truncal dykinesia, as well as a mildly festinated gait.
The patient was initially treated with levodopa 250 mg/carbidopa 25 mg, 5 times a day and ropinirole 6 mg once daily. However, he reported only marginal improvements with his tremor and continued to experience “OFF” episodes with sialorrhea and jaw tremor. Moreover, his sleep disturbance has been exacerbated by nocturia and rhinorrhoea despite the use of hypnotics including zolpidem and lemborexant.
Subsequently, Dr. Fung initiated treatment with safinamide 50 mg once daily which led to a reduction in end-of-dose tremor. While reducing the levodopa dose, the safinamide dose was gradually uptitrated to 50 mg twice daily, resulting in no sudden “OFF” symptoms and less dyskinesia. More importantly, patient’s quality of sleep also improved. Switching antihistamines further helped alleviate symptoms of the rhinorrhoea.
Overall, after the addition of safinamide for 4 months, there was a significant improvement in Parkinsonian symptoms, reduced sleep disturbances, and increased independent walking in this patient, and Dr. Fung commented that these could be attributed to the unique dopaminergic and glutamatergic modulation by safinamide.
Safinamide is an effective add-on therapy for PD patients experiencing wearing off, addressing both motor and non-motor symptoms, including sleep disturbance.
"Safinamide 50 mg twice daily resulted in no sudden 'OFF' symptoms and less dyskinesia"
Safinamide is a third-generation reversible monoamine oxidase-B inhibitor with additional activity on the glutamatergic pathway1. A prospective, open-label, single-arm study conducted in 5 centres in Spain evaluated the effectiveness of safinamide on sleep and daytime sleepiness in 50 PD patients with a mean age of 68.5 years. At 6 months, 44 patients completed the follow-up and most patients initially on safinamide 50 mg/day were switched to 100 mg/day by Month 3 (± 15 days). The outcomes were measured using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) scores at baseline and after Month 6 (± 1 months)1.
After 6 months of safinamide, the overall PSQI score reduced by 19.8% (from 10.43 ± 4.02 at baseline to 8.36 ± 4.41 at 6 months; p = 0.001). By domains, significant improvement were observed in PSQI-component 1-4 (PSQI-1 [subjective sleep quality] -23.9%, p = 0.009; PSQI-2 [sleep latency] -25.0%, p = 0.025; PSQI-3 [sleep duration] -40.0%, p = 0.01; and PSQI-4 [habitual sleep efficiency] -25.9%, p = 0.023) (Figure 1). Moreover, a significant reduction (−24.7%) in the ESS total score was observed1.
Figure 1: Mean score of individual PSQI score domains at baseline and after 6 months2. Note: PSQI-component 5-7 (step disturbances, use of sleeping medication and daytime dysfunction) are not included due to insignificant results1.
Similarly, a retrospective study at a University Hospital’s Movement Disorders Unit analysed the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms-Urinary subscale (SCOPA-AUT-U) in nondemented PD patients on safinamide 100 mg or other treatment regimens, and safinamide 100 mg was found to improve the total SCOPA-AUT-U as well as urgency, incontinence, frequency and nocturia subscale2.
Safinamide at 100 mg shows a promising effect by enhancing sleep and reducing daytime sleepiness among PD patients2, potentially by addressing urinary symptoms.
"Safinamide 100 mg improved symptoms of urgency, incontinence, frequency and nocturia"
References
1. Santos García D et al. Safinamide improves sleep and daytime sleepiness in Parkinson’s disease: results from the SAFINONMOTOR study. Neurol Sci 2022;43:2537–2544. 2. Gómez-López A et al. SURINPARK: safinamide for urinary symptoms in Parkinson’s disease. Brain Sci 2021;11: 57.
