Advanced Parkinson's disease often demands complex management strategies when oral pharmacotherapy fails to control motor fluctuations and dyskinesia. In routine clinical practice, clinicians frequently recommend device-aided therapies to re-establish continuous dopaminergic stimulation and restore quality of life. However, long-term therapeutic success depends heavily on treatment persistence and timely parameter optimization. Until recently, comparative real-world evidence evaluating retention across different advanced modalities remained scarce. To address this knowledge gap, the prospective multicenter DATs-PD GETM Spanish Registry systematically examined five distinct therapeutic modalities between January 2024 and May 2026. This comprehensive study evaluated 565 patients who initiated 591 treatments, delivering vital insights into clinical persistence and optimization dynamics.

Comparative Persistence Across Device-Aided Therapies

The multicenter registry evaluated five distinct device-aided therapies, including surgical deep brain stimulation, continuous subcutaneous apomorphine infusion, and continuous subcutaneous foslevodopa/foscarbidopa. Additionally, investigators assessed two enteral options: levodopa-carbidopa intestinal gel and levodopa-entacapone-carbidopa intestinal gel. Across the entire cohort, patients discontinued 170 out of 591 treatments, yielding an overall cessation rate of 28.8 percent.

However, remarkable differences emerged when comparing surgical intervention against continuous infusion modalities. Deep brain stimulation demonstrated exceptional durability, recording a discontinuation rate of only 4.1 percent. In contrast, continuous infusion systems exhibited substantially higher cessation rates. Specifically, continuous subcutaneous apomorphine infusion recorded a 34.1 percent discontinuation rate, while foslevodopa/foscarbidopa reached 34.7 percent. Similarly, levodopa-carbidopa intestinal gel and levodopa-entacapone-carbidopa intestinal gel showed cessation rates of 28.6 percent and 28.1 percent, respectively.

When researchers pooled all infusion therapies together, the overall discontinuation rate reached 33.6 percent. Importantly, statistical analysis revealed no significant differences in cessation rates or Kaplan-Meier persistence curves among the various infusion modalities. Consequently, these findings indicate that despite varied delivery routes, continuous infusion systems face nearly identical real-world retention challenges.

Primary Reasons Driving Treatment Discontinuation

Understanding why patients discontinue advanced treatments represents a crucial step toward improving clinical protocols. In this prospective registry, clinicians identified adverse events as the predominant trigger for treatment cessation, accounting for 38.2 percent of all discontinuations. For instance, subcutaneous infusion platforms frequently caused troublesome local dermatological reactions, including subcutaneous nodules and cellulitis. Meanwhile, enteral gel delivery systems occasionally induced gastrointestinal complications, pump malfunctions, or stoma site infections.

Furthermore, voluntary patient decision emerged as the second most common reason for stopping therapy, representing 25.3 percent of all cessations. Many individuals cited the physical burden of managing cumbersome pump equipment, restrictive tubing, and daily cassette preparation. Therefore, ergonomic friction and device complexity significantly undermine treatment adherence over extended periods. In contrast, deep brain stimulation rarely led to discontinuation, because the fully internalized system eliminates daily external handling.

Additionally, disease progression and emergent neuropsychiatric complications prompted treatment withdrawal in a smaller subset of patients. As neurodegeneration advances, emergent cognitive decline or severe visual hallucinations often complicate device maintenance. Consequently, proactive side-effect management and frequent patient communication remain vital to prevent premature therapy abandonment.

Divergent Optimization Timelines Across Modalities

Achieving optimal motor symptom control requires dedicated dose titration and device adjustment following initial initiation. Across the entire registry, the mean optimization period lasted 61.6 days, though timelines varied drastically across therapeutic modalities. For example, levodopa-entacapone-carbidopa intestinal gel demonstrated the fastest stabilization, requiring an average of only 19.6 days to achieve optimal dosing. This accelerated timeline likely reflects the familiar pharmacokinetics of enteral levodopa combined with catechol-O-methyltransferase inhibition.

In sharp contrast, deep brain stimulation demanded the longest adjustment timeframe, averaging 115.2 days to achieve full stabilization. This prolonged duration stems from the meticulous, iterative nature of neurostimulation programming. Neurologists must systematically adjust pulse width, frequency, and contact geometry while simultaneously tapering dopaminergic medications. Moreover, post-surgical brain tissue microlesion effects often delay final parameter stability for several weeks.

Meanwhile, subcutaneous infusion systems exhibited intermediate optimization intervals as teams balanced infusion rates with cutaneous tolerability. Clinicians must transparently communicate these temporal expectations to patients and families before initiating treatment. Therefore, setting realistic optimization timelines prevents premature frustration and enhances patient satisfaction during early management phases.

Clinical and Caregiving Predictors of Cessation

To establish which baseline characteristics predict premature treatment termination, investigators performed multivariable Cox proportional hazards regression analyses. Notably, the statistical model revealed that social and physical vulnerability substantially magnified the hazard of therapy cessation. Most prominently, institutional caregiving emerged as the strongest independent predictor, increasing discontinuation risk more than fivefold compared to home caregiving. Institutional environments frequently struggle with complex device protocols, rotating nursing staff, and limited specialized device training.

Additionally, intrinsic disease severity heavily influenced long-term therapeutic durability. Patients presenting with a higher Hoehn and Yahr stage during the ON state faced an 81 percent higher risk of treatment discontinuation. Advanced axial impairment and postural instability severely diminish personal autonomy, making complex pump operation remarkably challenging. Furthermore, longer daily OFF time at baseline also significantly heightened discontinuation likelihood, with each additional hour increasing the risk by roughly 9 percent.

Overall, these predictive factors demonstrate that severe motor disability and compromised support structures undermine device persistence. Consequently, clinicians cannot assess therapeutic suitability based solely on motor fluctuations. Instead, healthcare teams must evaluate caregiver capability, residence stability, and functional reserve before therapy selection.

Strategic Implications for Clinical Practice

These real-world findings carry immediate practical lessons for movement disorder specialists and general neurologists alike. Because one-third of patients stop continuous infusion therapies, healthcare providers should establish structured follow-up pathways during the vulnerable early months. Specifically, clinical centers must provide aggressive dermatological prevention strategies for subcutaneous infusions, such as rotating infusion sites and maintaining meticulous skin hygiene. Similarly, enteral pump programs require dedicated stoma care protocols and rapid technical troubleshooting support.

Moreover, the pronounced vulnerability of institutionalized patients calls for systemic improvements in residential care education. Neurologists should offer specialized pump training to nursing home staff, establishing clear protocols for tubing care and alarm management. Without institutional competence, even the most effective pharmacologic delivery systems risk rapid abandonment. Conversely, deep brain stimulation remains an exceptionally durable option for eligible candidates who can safely undergo intracranial surgery.

Finally, clinicians must recognize that real-world registries reflect clinical selection patterns rather than direct head-to-head superiority. Patients selected for deep brain stimulation are typically younger and possess fewer systemic comorbidities than those receiving intestinal gels. Therefore, personalized therapy selection must align device demands with patient lifestyle, caregiver resilience, and overall disease trajectory.

Frequently Asked Questions

What was the discontinuation rate for infusion therapies compared to DBS?

In this prospective registry, infusion treatments exhibited a combined discontinuation rate of 33.6 percent, with individual rates ranging between 28.1 percent and 34.7 percent. Conversely, deep brain stimulation demonstrated significantly superior persistence. Clinicians recorded a discontinuation rate of only 4.1 percent for deep brain stimulation, reflecting its durable long-term retention.

What were the most frequent reasons for stopping device therapies?

Adverse events constituted the primary driver of treatment discontinuation, accounting for 38.2 percent of all treatment cessations. In addition, patient preference played a major secondary role, driving 25.3 percent of treatment withdrawals. Consequently, clinicians must prioritize proactive adverse effect management and maintain continuous patient dialogue to optimize therapy retention over time.

Which clinical factors predicted a higher likelihood of discontinuation?

Multivariable Cox regression identified institutional caregiving as the strongest predictor of treatment discontinuation, increasing risk more than fivefold. Furthermore, higher ON-state Hoehn and Yahr stage and longer daily OFF time independently heightened discontinuation probability. Therefore, clinicians should closely evaluate functional dependency and caregiver support systems before selecting advanced therapeutic options.

Disclaimer: This content is for informational and educational purposes only... Refer to the latest local and national guidelines for clinical practice.

References

1. Santos García D et al. Discontinuation and optimization of device-aided therapies in Parkinson's disease: a prospective comparative real-world study. J Neurol. 2026 Nov 06. doi: 10.1007/s00415-026-14234-w. PMID: 42993214.
2. Santos-García D, Solleiro Vidal Á, Blázquez Estrada M, et al. Device-aided therapies (DATs) in Parkinson's disease (PD). The DATs-PD GETM Spanish Registry Protocol Study. PLoS One. 2025;20(3):e0316052.
3. Georgiev D, Trost M, Flisar D, et al. Long-term effect and reasons for switching and combining device-aided therapies in Parkinson's Disease. Neurol Neurochir Pol. 2025;59(1):15-28.