Today, I review, link to, and excerpt from The Polish Journal Of Neurology And Neurosurgery‘s “Dopamine agonist withdrawal syndrome — what do we really know?”.* [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Neurol Neurochir Pol. 2026;60(2):169-178. doi: 10.5603/pjnns.110733. Epub 2026 Mar 23.

*Note to myself: This is an outstanding brief review of the topic.

There are 101 similar articles in PubMed.

All that follows is from the above resource.

Table of content

• Abstract
• Introduction
• Diagnosis of DAWS
• Pathogenesis of DAWS
• DAWS and advanced therapies
• Treatment of DAWS
• Summary
• Article information
• References

Abstract

Introduction. Dopamine agonist withdrawal syndrome (DAWS) comprises a wide range of neuropsychiatric and autonomic symptoms that occur in temporal relation with the reduction or withdrawal of dopamine agonists (DAs) in a dose-dependent manner. This syndrome was described as an important complication in Parkinson’s disease (PD) and restless legs syndrome (RLS) treatment.

State of the art. Dopamine agonist withdrawal syndrome affects even up to 24% of PD patients treated with DAs in whom the medication was tapered. Predominant symptoms include the following: anxiety, depression, irritability, panic attacks, sleep disorders, and suicidal thoughts along with autonomic problems such as fatigue, orthostatic hypotension, nausea, and vomiting. Dopamine agonist withdrawal syndrome remains a therapeutic challenge as it is refractory to levodopa (LD), other PD therapies, anti-depressants, and anti-psychotics. The therapy-resistant syndrome may be a pitfall for patients trapped between intolerable side effects of DAs (impulse control disorder [ICD]) and withdrawal symptoms.

Clinical implications. Recognition of DAWS as a threatening condition is important for choosing the best treatment option for the patient. Due to the increasingly widespread use and efficacy of advanced therapies such as deep brain stimulation, enteral and subcutaneous LD, as well as apomorphine infusions, the risk of DAWS development should be considered. Dose reduction or discontinuation of DAs should be carefully planned and managed individually (personalized, based on main symptoms).

Future directions. Further research should focus on the natural evolution, risk factors, and duration of DAWS. Development of new generation DAs, such as tavapadon, which may reduce the side effects of dopaminergic therapy, may set new standards for treatment. Guidelines on the taper velocity of DAs, risk factors, and management therapies are to be established to improve detection and treatment of DAWS.

Keywords: Parkinson’s diseasedopamine agonistdopamine agonist withdrawal syndromeropinirolepramipexoledeep brain stimulationdepressionirritabilityanxietysleep disorders

Introduction

Dopamine agonists (DAs) are widely used drugs mostly utilized in the treatment of Parkinson’s disease (PD) and restless leg syndrome (RLS). They are used in monotherapy as well as in polytherapy. Dopamine agonists can be used at different stages of PD; nonetheless, they are currently not recommended as a first–line treatment for RLS due to the risk of augmentation [1, 2]. The methods of initiation and dosage are included in frequently updated therapeutic regimens, which may differ slightly in individual countries. As their clinical effects ameliorating motor symptoms can be satisfactory, their adverse effects such as neuropsychiatric (e.g., hallucinations, sleep attacks), behavioral (e.g., impulse control disorder, ICD), and autonomic (e.g., orthostatic hypotension) symptoms are not uncommon. Dopamine agonist withdrawal syndrome (DAWS) is classified as a wide range of neuropsychiatric and autonomic symptoms that may occur in temporal relation with the reduction or withdrawal of DAs in a dose–dependent manner [3–5]. It has been described both in patients suffering from PD and in those with RLS, which may suggest that it is more a drug than disease–drug interplay–related phenomenon. Dopamine agonist withdrawal syndrome was first described in 2010 by Rabinak and Nirenberg [5]. Available evidence demonstrates that 8 to 24% of PD patients treated with DAs in whom they were tapered may develop DAWS [6]. The published data on DAWS in RLS are unsatisfactory and mainly based on case reports. Dopamine agonist withdrawal syndrome may cause clinically significant, sociocultural distress and dysfunction. It is refractory to levodopa (LD) treatment and appears to be only alleviated by the reintroduction of DAs [7]. Clinically, DAWS can present in mild, moderate, and severe forms [8]. The most prominent and frequent symptoms of this syndrome are non–motor, such as the following: fatigue, anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal thoughts, drug cravings, orthostatic hypotension, nausea, vomiting, diaphoresis, an generalized pain (Tab. 1) [5].

Table 1. Symptoms of dopamine agonist withdrawal syndrome

Neuropsychiatric	Autonomic
Anxiety Depression Irritability Panic attacks Sleep disorders Insomnia Suicidal thoughts Dysphoria Agoraphobia Social phobia Anhedonia Drug cravings	Fatigue Orthostatic hypotension Nausea and vomiting Hyperhidrosis Flushing Generalized pain

The agreed–upon risk factors for the development and severity of DAWS include mainly the following: high cumulative DAs exposure, higher baseline dose of DAs, higher peak DAs doses (≥ 150 mg levodopa equivalent daily dose [LEDD]), and total dopaminergic medication load [9]. Nevertheless, the DAs–introduction–preceding risk factors, mechanism, as well as the management of DAWS are still poorly understood. There is no gold–standard management of DAWS [10]. It may significantly impact the patient’s as well as the caregiver’s life, and may influence healthcare systems and costs of therapy of these patient populations. Thus, it is of upmost validity to detect this syndrome. Exploration of DAWS may contribute to the new approach to treatment strategies of PD and RLS (initiation, titration, maintenance and reduction of dose, and introduction of concomitant therapies). It may be highly important when advanced therapies are initiated (e.g., deep brain stimulation [DBS] or pump therapies utilizing LD) and DAs are too vigorously reduced. The aim of this paper is to provide a comprehensive literature review on DAWS — from possible molecular mechanisms, prevalence, symptoms, and influence of the type of DAs, to the management and interactions between therapies. Due to the lack of systematic studies on DAWS related to DAs withdrawal in RLS patients, in this paper we focus on this problem in PD only.

Summary

Dopamine agonist withdrawal syndrome is a specific condition related to DAs dose reduction and/or withdrawal. Its pathogenesis is poorly understood, as well as its prevalence and risk factors. Nevertheless, the devastating neuropsychiatric and autonomic consequences may be serious (even life threatening), long–lasting, and refractory to common interventions. Re–introduction of DAs is suggested to be an option. Nevertheless, the most important management is the slow–as–possible tapering of DAs, and only when necessary. It seems that in selected cases, appropriate rehabilitation (in the meaning of psychotherapy and physiotherapy) may produce as good or even better results than pharmacological modulation. The introduction of next–generation DAs (now still in clinical trials) like tavapadon, which focuses on more selective receptor targeting to reduce side effects, and being a D1/D5 partial agonist, shows promise for fewer side effects, including DAWS, as well as ICD and sleepiness, when compared to older D2/D3 agonists [50].