On-demand therapies–emergency medication or daily routine?

Abstract Fluctuations represent a major therapeutic challenge in Parkinson’s disease (PD) and become increasingly prevalent with disease progression. While oral and device-aided therapies (DAT) improve symptom control, patients continue to experience disabling OFF episodes, in particular early morning OFFs, delayed ON, and no-ON phenomena. Increasing evidence suggests that both motor and non-motor fluctuations are more common than previously recognized and contribute substantially to impaired quality of life. Fluctuations affect up to 50% of patients within five years of disease onset to eventually affect almost all patients with longer duration. Beside altered central pharmacodynamics, peripheral mechanisms such as dysphagia, gastroparesis, altered intestinal absorption, and microbiome-mediated levodopa degradation, contribute to fluctuations. Although oral adjunct medication and DAT reduce daily OFF-time, clinically meaningful OFF periods often persist. This is where on-demand therapies provide rapid symptom relief and address the limitations of conventional oral medication and DAT. Hence, more regular, even daily use of on-demand therapies may improve quality of life in patients with PD. However, the potential impact of on-demand therapies on non-motor OFF periods needs further investigation. Side effects, handling and economic considerations should be taken into account. This expert perspective concludes that given the high prevalence and clinical relevance of fluctuations, on-demand therapies may be considered as an integral component of standard PD management rather than solely as a rescue option in rare emergency situations. Implementation may be particularly beneficial for patients experiencing early-morning-OFFs, delayed and no-ONs but also predictable and unpredictable OFFs.