Dopamine Agonist Withdrawal Syndrome Research Articles

Suicide Attempt in a Case of Dopamine Agonist Withdrawal Syndrome in Parkinson's Disease

Suicide Attempt in a Case of Dopamine Agonist Withdrawal Syndrome in Parkinson's Disease

Rasagiline Withdrawal Syndrome in Parkinson's Disease.

Parkinson’s disease (PD) patients using dopamine agonists can develop withdrawal symptoms, referred to as dopamine agonist withdrawal syndrome (DAWS), under dose tapering or discontinuation of these drugs. DAWS includes a severe stereotypical cluster of psychiatric and psychological symptoms encompassing severe mood and anxiety disturbances, autonomic symptoms, as well as generalized pain and drug cravings. However, symptoms of withdrawal of dopamine replacement therapies (DRT) are not simply limited to dopamine agonists tapering, as observed in PD patients on deep brain stimulation after dopaminergic drugs withdrawal related to surgery. To date, no DRT-related withdrawal syndrome has been described in PD patients who discontinue rasagiline, an irreversible inhibitor of monoamine oxidase-B (MAO-B). Here we report three PD patients who developed a severe withdrawal syndrome after rasagiline suspension. The syndrome was mainly characterized by prominent psychiatric disorders (depression, anxiety with panic attacks, dysphoria, and agitation) associated with fatigue, generalized pain, and autonomic manifestations (closely resembling symptoms of DAWS). In our opinion, this report suggests the importance of closely monitoring PD patients undergoing rasagiline suspension for withdrawal symptoms and provides interesting points of reflection on the role of rasagiline and other MAO-B inhibitors in mood disorders.

Dopamine agonist withdrawal syndrome associated factors: A retrospective chart review

Dopamine agonist withdrawal syndrome (DAWS) has been introduced to describe the constellation of symptoms resulting from reduction or suspension of dopamine agonist medications. In patients with Parkinson’s disease (PD) the impact of DAWS can be significant in terms of distress and disability. Unfortunately, no standard treatment exists other than reintroduce the dopamine agonist even in the presence of adverse effects. Therefore, identification of vulnerable patients would be beneficial. Previous studies have linked DAWS with impulse control disorder behavior (ICD), higher dopamine agonist doses, and milder motor impairment in PD patients.We conducted a retrospective chart reviewof PD patients treated with dopamine agonist. A total of 313 charts from January 2011 to December 2013 were reviewed, showing 126 patients who were discontinued from dopamine agonist. Twenty-one patients (16.8 %) fulfilled the diagnostic criteria for DAWS. Factors associated with the occurrence of DAWS were: (1) dose of dopamine agonist ≥150 mg expressed in levodopa equivalents daily dose (LEDD) (p = 0.018), (2) impulse control disorder as an adverse effect to dopamine agonist (p = 0.002), and (3) prior deep brain stimulation (DBS) (p = 0.049). The probability of developing DAWS in the presence of all 3 identified factors was 92 %; presence of 2 factors raised the probability up to 70 %; the presence of one factor increased the probability up to 30 %. In the absence of these 3 factors the probability of developing DAWS was 3 %. Prospective studies are warranted to confirm these findings.

Implications of dopaminergic medication withdrawal in Parkinson's disease.

The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson’s disease (PD) is variable and doses may need to be increased, but also tapered. The plan for dose adjustment is usually done as per drug information recommendations from the licensing bodies, but there are no clear guidelines with regards to the best practice regarding the tapering off schedule given sudden dose reductions of drugs such as dopamine agonists may have serious adverse consequences. A systematic literature search was, therefore, performed to derive recommendations and the data show that there are no controlled studies or evidence-based recommendations how to taper or discontinue PD medication in a systematic manner. Most of the data were available on the dopamine agonist withdrawal syndrome (DAWS) and we found only two instructions on how to reduce pramipexole and rotigotine published by the EMA. We suggest that based on the available data, levodopa, dopamine agonists (DA), and amantadine should not be discontinued abruptly. Abrupt or sudden reduction of DA or amantadine in particular can lead to severe life-threatening withdrawal symptoms. Tapering off levodopa, COMT inhibitors, and MAO-B inhibitors may worsen motor and non-motor symptoms. Based on our clinical experience, we have proposed how to reduce PD medication and this work will form the basis of a future Delphi panel to define the recommendations in a consensus.

Summary Safety Review: dopamine agonist withdrawal syndrome

Summary Safety Review: dopamine agonist withdrawal syndrome

Impact of behavioral side effects on the management of Parkinson patients treated with dopamine agonists

Dopamine agonists are one of the main stay of treatment option for Parkinson disease (PD). Side effects that develop from their use are generally categorized into behavioral and non-behavioral. Behavioral side effects include: impulse control behavior disorder (ICD), psychosis and cognitive impairment. Non-behavioral side effects include: nausea/vomiting, “sleep attacks”, leg swelling, weight gain and orthostasis. The aim of this study is to evaluate the clinicians’ response to PD patients who developed behavioral side effects from dopamine agonists, in comparison to those patients who developed only non-behavioral side effects. We performed a retrospective chart review of all patients diagnosed with PD over a two year period. Among 313 patients who were on a dopamine agonist, 156 reported side effects. Sixty-five patients reported behavioral (with or without non-behavioral) side effects, while 91 experienced only non-behavioral side effects. Forty-nine out of the 65 patients (75.3%) who experienced behavioral side effects had their dopamine agonist dose decreased compared to 53 out of 91patients (58.2%) who experienced only non-behavioral side effects (Chi square = 4.92, p < 0.05). Patients with behavioral side effects were 3 times more likely have their dose decreased (OR = 3.3; 95%CI = 1.442–7.551; P = 0.005). However, neither taper speed nor the occurrence of dopamine agonist withdrawal syndrome (DAWS) differed between the two groups. Amongst PD patients treated with dopamine agonists, the presence of behavioral side effects independently increased the chance of dopamine agonist dose reduction. Prospective studies are needed to confirm these findings.

Management of Impulse Control Disorders with Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease

Impulse Control Disorders (ICDs) and related disorders are common side effects of dopaminergic treatment in Parkinson's Disease (PD) and are associated with negative effects on mental and physical health, quality of life and interpersonal relationships. Current management options are limited, as a reduction of dopaminergic medication often leads to worsening of motor symptoms or dopamine agonist withdrawal syndrome. The aim of this review was to investigate if ICDs improve, worsen, or remain stable after Subthalamic Nucleus Deep Brain Stimulation (STN-DBS). We reviewed retrospective, prospective and randomized-controlled studies published between 2000 and 2019 examining the effect of STN-DBS on one or more ICDs. The number of participants, time of follow-up, methods used to measure ICDs, type of ICDs, the incidence of ICDs before STN-DBS, the incidence of improvement (remission or reduction) of ICDs after STN-DBS, the incidence of de novo ICDs after STN-DBS, stimulation parameters, lead position, change in motor score and change in medication are reported for each study. Available studies suggest that ICDs improve after STN-DBS in most patients and that persisting new-onset ICDs induced by STN-DBS are rare. However, more randomized-controlled studies are needed to confirm the findings and to further investigate the underlying mechanisms.

Challenges in ICU Care: The Patient With Parkinson's Disease.

Patients with Parkinson's disease (PD) face unique challenges when admitted to the hospital. The nature of the disease, complexity of the pharmacotherapeutic home regimens, and the medication-related policies of institutionalized care all contribute to the challenges patients and providers face. In addition, medication errors are common in this population. Incorrectly ordered or omitted home medications or delayed administration can have significant negative consequences including worsening of PD symptoms, dopamine agonist withdrawal syndrome, or malignant or hyperpyrexia syndrome. Also, this patient population may commonly encounter contraindicated medications ordered during their hospitalizations. These medication misadventures negatively affect patient care, which may lead to increased length of stay and significant adverse sequalae. Nurses, pharmacists, and other health care providers can help ease the anxiety of patients and their families by taking detailed medication histories, restarting home medication regimens, customizing medication administration to fit patients' needs, and screening patient profiles for drug-drug and drug-disease interactions. Education of hospital staff regarding the unique needs of this patient population and seeking the advice of specialists in PD can also promote improved patient care.

Neuropsychiatric symptoms in Parkinson's disease: aetiology, diagnosis and treatment

SUMMARYHistorically, Parkinson's disease was viewed as a motor disorder and it is only in recent years that the spectrum of non-motor disorders associated with the condition has been fully recognised. There is a broad scope of neuropsychiatric manifestations, including depression, anxiety, apathy, psychosis and cognitive impairment. Patients are more predisposed to delirium, and Parkinson's disease treatments give rise to specific syndromes, including impulse control disorders, dopamine agonist withdrawal syndrome and dopamine dysregulation syndrome. This article gives a broad overview of the spectrum of these conditions, describes the association with severity of Parkinson's disease and the degree to which dopaminergic degeneration and/or treatment influence symptoms. We highlight useful assessment scales that inform diagnosis and current treatment strategies to ameliorate these troublesome symptoms, which frequently negatively affect quality of life.

Behavioural and trait changes in parkinsonian patients with impulse control disorder after switching from dopamine agonist to levodopa therapy: results of REIN-PD trial

ObjectiveIn this multicentre open-label trial, we compared behavioural and neuropsychiatric symptoms in Parkinson’s disease (PD) patients with impulse control disorders (ICD) treated with dopamine agonists before and 12 weeks after...

Dopamine agonist withdrawal syndrome (DAWS) in a tertiary Parkinson disease treatment center

IntroductionDopamine agonists are a mainstay of treatment for patients with Parkinson disease (PD). However, side effects limit their use, often necessitating dose change. Upon withdrawal, patients may experience dopamine agonist withdrawal syndrome (DAWS). To date, there is no established protocol for the prevention or treatment of DAWS. MethodsWe performed a retrospective chart review of PD patients who were taking a dopamine agonist. ResultsIn our large cohort of 313 PD patients who were on a dopamine agonist, we found that 39.5% (n=124) had a change in their dose of medication for various reasons, including 102 patients who experienced a side effect on a dopamine agonist. Twenty out of 102 patients (19.6%) developed symptoms consistent with DAWS, whereas 1 out of 22 patients (4.5%) who had medication dose changed due to any other reason (e.g. dyskinesias, DBS surgery, decreased by another provider, etc.) developed symptoms consistent with DAWS. Our DAWS population had a shorter duration of PD, less exposure to a dopamine agonist, and was on a lower dose compared to those patients who did not develop DAWS. Agitation was the most common DAWS symptom reported in our cohort. Interestingly, in terms of developing DAWS, the prevalence of DAWS (19.0% vs 16.5%; p=0.76) between partial versus total discontinuation was not significantly different whether the dopamine agonist dose was decreased (21 patients) or completely stopped (103 patients). ConclusionContrary to previous reports, we have found that other side effects besides impulse control behavioral disorders also increase risk for developing DAWS. Furthermore, the prevalence of DAWS did not differ between partial versus total discontinuation of the dopamine agonist.

Acute Presentation of Nonmotor Symptoms in Parkinson's Disease.

There are a few syndromes involving the nonmotor symptoms of Parkinson's disease and other movement disorders that can quickly lead to severe morbidity and mortality, and, as such, need rapid identification and management. Among these are neuroleptic malignant syndrome, serotonin syndrome, dopamine agonist withdrawal syndrome, and dystonic storm. It is important to maintain a high index of suspicion for these disorders as lack of identification can lead to death. Many of these acutely occurring nonmotor syndromes are primarily the result of imbalances in dopaminergic and serotonergic systems due to changes in pharmacologic management of psychiatric disorders or Parkinson's disease. We discuss these acutely occurring nonmotor symptoms in order to raise awareness and also to highlight how these extremes in symptoms may uniquely shed light on the pathophysiology of Parkinson's disease.

Augmentation and impulsive behaviors in restless legs syndrome: Coexistence or association?

Editors' Note: In WriteClick this week, Dr. Nirenberg responds to “Augmentation and impulsive behaviors in restless legs syndrome: Coexistence or association?” with the hypothesis that augmentation in restless legs syndrome may be a forme fruste of dopamine agonist withdrawal syndrome. Authors Djamshidian et al. report no association between augmentation and medication nonadherence, but agree with monitoring these patients closely for addictive behaviors. In reference to “Spatial-temporal functional mapping of language at the bedside with electrocorticography,” Drs. Babajani-Feremi et al. and authors Wang et al. discuss the use of high-gamma …

Spatial-temporal functional mapping of language at the bedside with electrocorticography.

Editors' Note: In WriteClick this week, Dr. Nirenberg responds to “Augmentation and impulsive behaviors in restless legs syndrome: Coexistence or association?” with the hypothesis that augmentation in restless legs syndrome may be a forme fruste of dopamine agonist withdrawal syndrome. Authors Djamshidian et al. report no association between augmentation and medication nonadherence, but agree with monitoring these patients closely for addictive behaviors. In reference to “Spatial-temporal functional mapping of language at the bedside with electrocorticography,” Drs. Babajani-Feremi et al. and authors Wang et al. discuss the use of high-gamma electrocorticography, electrocortical stimulation mapping, …

Introduction to Parkinson disease (PD) and its complications.

Parkinson disease (PD) is a common neurodegenerative disorder in older adults characterized by motor and nonmotor symptoms and complications. Impulse control disorders (ICDs), such as pathological gambling, compulsive shopping, compulsive sexual behavior (hypersexuality), and binge eating disorder, affect 13.6% of the PD population. Use of dopamine receptor agonists (DRAs) is considered a major risk factor for ICD development. Amantadine and a high dose of levodopa were linked to ICDs to a lesser extent than DRAs. Based on the severity of behavior(s), ICDs can negatively impact social, professional, and familial lives of patients and their families. Ideally, all PD patients taking DRAs, high doses of levodopa, and/or amantadine should be routinely asked about or monitored for ICDs during therapy initiation and continuation. Dose decrease or withdrawal of the offending agent, primarily DRAs, is usually the most effective first step in ICD management. Careful dose adjustment with close monitoring is warranted due to risk for worsening of motor symptoms or emergence of dopamine agonist withdrawal syndrome (DAWS). About 1/3 of PD patients with ICD who decrease or discontinue DRA experienced DAWS. The lowest dose of DRA will need to be continued to balance ICDs and DAWS as it is not alleviated by other dopaminergic or psychotropic medications. Other therapies with low empiric evidence, such as amantadine, naloxone, cognitive behavior therapy, deep brain stimulation, and psychopharmacotherapy showed mixed results for ICD management. It is crucial that clinicians are familiar with the psychiatric complications of PD, including ICDs, beyond mere recognition and management of motor symptoms.

The Agony of the Agonists: a Review of Impulsivity and Withdrawal Syndromes in Parkinson's Disease Treatment

The introduction of dopamine agonists was a welcome development in the treatment of Parkinson's disease. However, their history has been somewhat checkered with concerns about their side effects including sudden onset of sleep and ‘sleep attacks’ the development of fibrotic side effects with ergot-derived agents; and most recently, the emergence of impulse control disorders. Furthermore, those who develop these behaviors are those most likely to suffer distressing side effects on their withdrawal: the so-called ‘dopamine agonist withdrawal syndrome’ (DAWS). This review examines this complex area and some suggested strategies to avoid and manage these phenomena, and concludes with some discussion of the future agenda for improving the understanding and management of these conditions.

Developments in impulse control behaviours of Parkinson's disease.

Impulse control behaviours (ICBs) are a frequent comorbidity for patients with Parkinson's disease. They consist of impulse control disorders, dopamine dysregulation syndrome, and punding. The field continues to evolve in the understanding of impulsivity and assessment of risk factors in the development of these behaviours and their appropriate management in patients with Parkinson's disease. Impulsivity is a multifaceted concept that is surprisingly common in untreated patients with Parkinson's disease. The incidence of ICBs increases with demographic, clinical, and biochemical risk factors. Treatments rely on reduction of dopamine agonists with exception of cognitive behavioural therapy and possibly repetitive transcranial magnetic stimulation. Reduction of dopamine agonist dose is the mainstay of treatment of ICBs. Other forms of dopaminergic treatment such as deep brain stimulation or jejunal infusion are alternative treatments but may be complicated by dopamine agonist withdrawal syndrome. Other therapies show promise but data are insufficient to suggest their regular use.

Dopamine agonist withdrawal syndrome (DAWS) symptoms in Parkinson's disease patients treated with levodopa–carbidopa intestinal gel infusion

Levodopa-carbidopa intestinal gel infusion (LCIG) is indicated in patients with advanced levodopa-responsive Parkinson's disease (PD) for the treatment of motor fluctuations and dyskinesias unsatisfactorily managed with conventional medication. The outcome of non-motor symptoms - particularly affective and behavioral ones - following LCIG initiation remains scarcely explored, especially with respect to the changes undergone by oral dopaminergic drugs. Here we describe 4 PD patients who developed dopamine agonist withdrawal syndrome (DAWS) symptoms correlated with rapid taper of these drugs after LCIG initiation. We identified 4 cases developing apathy and depression after the rapid withdrawal of Dopamine agonists (DAs) consequent to LCIG introduction. The clinical data were obtained through detailed review of medical records. Within few days after DAs withdrawal, all 4 patients developed apathy, anhedonia and depression, despite the marked reduction of dyskinesias and the improvement of motor fluctuations after LCIG introduction. We unsuccessfully tried to manage these and other DAWS symptoms by increasing LCIG flow. Within 6 months, all patients spontaneously presented a slow but gradual improvement of DAWS symptoms, not requiring any further treatment strategy or LCIG discontinuation. To our knowledge, this is the first report describing the occurrence of DAWS symptoms in advanced PD patients after DAs withdrawal in LCIG and highlighting the difficulty of distinguishing postoperative effects from drug withdrawal symptoms. Therefore we wish to draw attention of clinicians to the risk of developing DAWS in advanced PD patients switched to LCIG monotherapy. In such cases, a rapid taper of DAs should be avoided.

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

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 1month in 51 patients (33male; mean age: 73.0±9.9years; PD duration: 12.2±6.3years) 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.

Management of impulse control disorders in Parkinson's disease: Controversies and future approaches.

Impulse control disorders in Parkinson's disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies, including the role of more recently available anti-parkinsonian drugs, and potential future approaches involving routes of drug delivery, nonpharmacological treatments (such as cognitive behavioral therapy and deep brain stimulation), and other as yet experimental strategies.