Change in Swallowing Function and Substance P Levels Associated with Nicergoline in Neurological Disease: A Pilot Study

Background/Objectives: Dysphagia is a prevalent consequence of neurological conditions, particularly stroke and Parkinson’s disease, leading to aspiration pneumonia and reduced quality of life. Currently, there are no specific recommendations for pharmacological therapy, although studies indicate that elevated substance P levels may improve swallowing function. While nicergoline is known to increase substance P, the role of its major metabolite, 10-methoxy-dihydro-lysergol (MDL), in this therapeutic effect remains unclear. This study examined the therapeutic effects of nicergoline and its correlation with substance P and MDL levels. Methods: This study conducted an open-label pilot study with historical controls in neurogenic patients with dysphagia. The primary outcome was improvement in the Gugging Swallowing Screen (GUSS) scores at week 12. Secondary outcomes included choking frequency, serum substance P levels, and the correlation between serum MDL levels and dysphagia enhancement. Inverse Probability Weighting (IPW) was employed to adjust for baseline confounders. Results: A total of 92 patients were analyzed: 26 in the nicergoline group (20 or 60 mg/day) and 66 in the historical control group. Compared to controls, the nicergoline group exhibited significantly higher median of GUSS scores (20 (IQR: 19–20) vs. 15 (IQR: 9–19), p < 0.001) and significantly lower median of choking frequency (6.43 (IQR 0–17) vs. 108 (IQR 13–201) 105.22, p < 0.001). The median substance P concentration in the therapy group was 4089.15 (IQR: 3336.13–4468.26) pg/mL. Patients receiving nicergoline showed a statistically significant elevation in substance P from baseline (p < 0.001). Pearson analysis revealed a negligible correlation between serum MDL and substance P levels (R2 = 0.0349). Conclusions: Preliminary findings suggest that nicergoline may be associated with improvements in swallowing function in neurogenic dysphagia and a potential increase in substance P levels. The lack of correlation with serum MDL suggests that efficacy may not linearly depend on circulating metabolite concentrations. Further large-scale randomized controlled trials are warranted.