A Pilot Prospective, Multicenter Observational Study of Dopamine Agonist Withdrawal Syndrome in Parkinson's Disease

Abstract

Dopamine agonist withdrawal syndrome (DAWS) has been reported in patients with Parkinson's disease (PD) who rapidly decrease or stop their dopamine agonist (DA) treatment. Retrospective studies suggest a high prevalence of DAWS (14%-18%) in PD, but there are no prospective studies. We report data from the first pilot European multicenter prospective study addressing the frequency of probable DAWS (Rabinak-Nirenberg criteria) in PD patients. The self-completed Nonmotor Symptoms Questionnaire (which addresses the core features of DAWS) was administered at clinical follow-up at 1 month in 51 patients (33 male; mean age: 73.0 AE 9.9 years; PD duration: 12.2 AE 6.3 years) who had discontinued dopamine agonists. Twelve out of fifty-one patients (24%) met clinical criteria for DAWS, the most common symptoms of which were anxiety (91.7%), pain (50%), sweating (41.7%), and anhedonia (16.7%), after the withdrawal of a DA (ropinirole, pramipexole, or cabergoline). In this first prospective evaluation of DAWS in the clinic, preliminary data indicate a high rate after discontinuation of a range of DAs, particularly in the context of impulse control disorders. Larger, controlled studies are required to establish a definitive management pathway.Dopamine agonist withdrawal syndrome (DAWS) has emerged as a therapeutic challenge in Parkinson's disease (PD). The reported symptoms are stereotyped and consist of psychiatric, autonomic, and sensory symptoms, similar to those of addictive drug withdrawal. 1 The condition has been recently characterized and described in people with PD who decrease or stop their dopamine agonist (DA) treatment. 2,3 A prevalence of DAWS of 14% to 18% in PD patients who taper a DA has been reported in retrospective studies, with an even higher prevalence in those who taper a DA in the setting of baseline impulse control disorders. 1,2 At this time, we are not aware of any prospective studies addressing the frequency of this problem in the clinic. We report a prospective, multicenter, observational study that specifically addressed occurrence of DAWS in consecutive PD patients on DA treatment who underwent stoppage of DA treatment using the DAWS criteria defined by Rabinak and Nirenberg, supplemented by relevant questions on the Nonmotor Symptoms Questionnaire (NMSQuest). 4 Patients and MethodsFor a period of 6 months (November 2012-May 2013, all PD patients whose DA treatment was tapered and stopped were specifically monitored for development of DAWS by investigators in 10 centers across Europe. The criteria used for development of DAWS were pragmatic and were based on the expert advice and guidelines reported by Rabinak 1 and utilized the use of the NMSQuest, a validated self-reported nonmotor symptoms (NMS) tool addressing 30 NMS. 4 NMSQuest contains questions in a "yes" and "no" format that are described as typical symptoms of DAWS. In addition, in all suspected DAWS

A European multicentre survey of impulse control behaviours in Parkinson's disease patients treated with short‐ and long‐acting dopamine agonists

“…Overall a low ICD rate of 9% was reported with only 2.8% graded as severe ICD requiring discontinuation of RTG. This observation also reinforces the clinical concept that, in many patients, DAs can indeed be continued despite ICDs but with close monitoring and education of patient and carer thus avoiding the damaging clinical and psychological effect of DAWS . This concept underpins the recent recommendation for management of ICDs .…”

Implications of dopaminergic medication withdrawal in Parkinson’s disease

“…In part, this is driven by the heightened awareness of the damaging and medicolegally relevant risk of impulse control disorder (ICD) and dysregulation behavioral syndromes emerging with the use of DAs. As a result, neurologists or health care professionals may sometimes reduce or discontinue a DA too quickly or abruptly in PD patients leading to dangerous complications such as dopamine agonist withdrawal syndrome (DAWS), which can be life-threatening in extreme cases (Rabinak and Nirenberg 2010 ; Nirenberg 2013 ; Ray Chaudhuri et al 2015 ; Yu and Fernandez 2017 ;). The stoppage of oral DA abruptly can also occur in severely ill PD patients where the patient is unable to take drugs orally and have been recently highlighted in a number of patients being admitted with severe COVID-19 infection (Antonini et al 2020 ).…”

Rotigotine Transdermal Patch for Motor and Non-motor Parkinson’s Disease: A Review of 12 Years’ Clinical Experience

“…Rotigotine is considered the least likely DA to cause ICDs. Therefore, it should be regarded as the first option among DAs, especially in patients with an ICD history or where DAWS [ 137 ] is a possibility. If a patient is already taking other DAs and is experiencing ICDs, a switch to rotigotine could be considered if there is a clinical need to continue DAs.…”