Rotigotine patch prescription in inpatients with Parkinson’s disease: evaluating prescription accuracy, delirium and end-of-life use

Background Rotigotine patch, a trans-dermal dopamine agonist, is used acutely to replace oral dopaminergic medications for inpatients with Parkinson’s disease where enteral routes are no longer available, and is also an option in end-of-life care where patients can no longer swallow. Concerns regarding acute use of Rotigotine include difficulty achieving dopaminergic equivalence, promotion of delirium/hallucinations and promotion of terminal agitation. Objective our objectives were to establish: (i) accuracy of Rotigotine prescribing, (ii) rates of delirium/hallucinations and (iii) rates of terminal agitation. Method we retrospectively evaluated the use of Rotigotine in an inpatient population at a UK teaching hospital. Prescriptions between January 2018 and July 2019 were identified and inpatient records were analysed. OPTIMAL Calculator 2 was used as a gold standard for assessing conversion of oral dopaminergic medication to Rotigotine. Results a total of 84 inpatients were included. 25 (30%) patients were prescribed the recommended dose of Rotigotine; 31 (37%) higher and 28 (33%) lower than recommended. A total of 15 of 41 (37%) patients with dementia and 22 of 49 (45%) patients with delirium before initiation of Rotigotine inappropriately received the higher dose; 20 (24%) patients developed new/worsening delirium and 8 (10%) patients developed new/worsening hallucinations; and 59 (70%) patients were dead at time of evaluation, of these 40 (68%) died in hospital, 10 (25%) of whom experienced terminal agitation. Conclusions acute conversion of oral dopaminergic medication to trans-dermal Rotigotine patch remains problematic despite the availability of validated tools. Inappropriate dosing may precipitate or worsen delirium/hallucinations. Use at end-of-life requires further evaluation.

64 Evaluating the Acute use of Rotigotine Patch for Dopaminergic Replacement in An Inpatient Population

Introduction Rotigotine, a trans-dermal dopamine agonist (DA), can be used acutely for inpatient populations and is an option in end of life (EoL) care for people with Parkinson’s disease (PD) where enteral (oral or naso-gastric) routes are no longer available or appropriate. Concerns regarding acute use of DAs in hospital include: i) difficulty achieving dopaminergic equivalence; ii) promotion of delirium; and iii) promotion of terminal agitation at EoL. Methods We retrospectively evaluated acute inpatient Rotigotine use in a UK teaching hospital. Prescriptions between January-June 2018 were identified from the pharmacy database and relevant inpatient records were analysed. The OPTIMAL calculator was used as a gold standard for dopaminergic conversion. Results 33 eligible inpatients were identified. 13 (39%) patients were prescribed the recommended dose of Rotigotine; 7 (21%) higher and 13 (39%) lower than recommended dose. Of 22 (66%) patients with delirium, 18 (82%) inappropriately received the higher dose. 12 (36%) patients developed new or worsening delirium; and 6 (18%) developed new or worsening hallucinations. 19 (58%) patients were dead at time of evaluation with median survival of 22 days (range 1-207). For patients prescribed Rotigotine for EoL (n=13), median survival was 15 days (range 1-62); for patients not prescribed Rotigotine for EoL (n=20), median survival was 81 days (range 6-207). Of 13 (39%) patients prescribed Rotigotine for EoL, 9 (69%) had evidence of terminal agitation. Conclusions Acute conversion to Rotigotine remains problematic, despite availability of validated tools. Inappropriate dosing may precipitate or worsen delirium. Acute prescription of Rotigotine appears to act as a proxy marker for poor prognosis and could be a red flag for triggering advanced care planning. Little is published regarding use of Rotigotine at EoL, this data raises concerns regarding risk of terminal agitation and is an important area for further study.

Pathologic Behaviors Provoked by Dopamine Agonist Drugs: Gambling, Sex, Eating, and Spending

Dopamine agonists are synthetic medications that stimulate dopamine receptors. They are commonly used for treatment of Parkinson’s disease and in lower doses for restless legs syndrome. This drug class includes pramipexole (Mirapex), ropinirole (Requip), and the rotigotine patch (Neupro). These drugs have special properties, with unique adverse effects that are not intuitively associated with the drug. Hence, a brief chapter is devoted to these side effects. If the patient is not taking one of these medications, this chapter may be skipped. Several years ago clinicians recognized that pramipexole and ropinirole were associated with the development of pathologic gambling. Insidiously, a minority of people who were prescribed these medications began experiencing the desire to gamble, such as at casinos or online. For some, this was an exacerbation of prior tendencies, but for others this desire came out of the blue, with no prior gambling history. Other types of compulsive pathologic behaviors soon were also recognized in some people treated with these drugs. This included inappropriate hypersexual behavior (extramarital affairs, pornography) and compulsive spending, eating, drinking, or smoking. In many people, this behavior was completely out of character. The common element was the initiation of pramipexole or ropinirole. The behaviors did not develop immediately, but insidiously became apparent after the medication was slowly escalated into the therapeutic range. Patients and family were often oblivious to the behavior or relation to the drug until specifically asked about it in the doctor’s office. The common theme among these compulsive behaviors is that they are inherently rewarding human experiences. It became recognized that use of these dopamine agonist drugs by some people was associated with a pathologic drive to excessively engage in such activities as gambling, sex, eating, or spending. For affected people, this began to dominate their thoughts and actions. Who would think that a drug could drive specific hedonistic or rewarding behaviors? Experience in the clinic and published evidence, however, corroborates this risk. The two primary agents that have been implicated are pramipexole (Mirapex) and ropinirole (Requip). The rotigotine patch has also been associated with such behaviors, but apparently less frequently.