Safety considerations when using non-ergot dopamine agonists to treat Parkinson’s disease

ABSTRACT

Introduction

Nonergot dopamine agonists (NEDA) represent an excellent treatment option for Parkinson’s disease (PD) patients, in both early and advanced stages of the disease. The post-marketing phase of NEDA has highlighted, though, the occurrence of important long-term adverse events.

Areas covered

This review reports recent updates on NEDA adverse events, analyzing neurobiological bases and risk factors of these complications. A literature search has been performed using Medline and reviewing the bibliographies of selected articles.

Expert opinion

NEDA represents a very important option in the treatment of PD. Criticisms on their use can be overcome through a better knowledge of these molecules and of the risk factors for adverse events which allow specialists to prevent the occurrence of undesired complications and consent a tailor-based approach.

Abbreviations: PD: Parkinson’s disease, DA: dopamine agonists, NEDA: non-ergot dopamine agonists, ICD: impulse control disorders, DAWS: dopamine agonist withdrawal syndrome, CYP: Cytochrome P, PK: pharmacokinetic, AUC: area under the curve, HRT: hormone replacement therapy, AV: atrioventricular, HF: heart failure, OH: orthostatic hypotension, RBD: REM behavior disorders, PDP: Parkinson’s disease psychosis, DRT: dopamine replacement therapy, DDS: dopamine dysregulation syndrome, MMSE: Mini-Mental state examination, EDS: excessive daytime somnolence.

KEYWORDS:

• Dopamine agonists
• impulse control disorders
• heart failure
• non ergot derivatives
• parkinson’s disease
• safety
• side effects
• safety3

Article highlights

• All dopamine agonists have demonstrated to significantly improve motor symptoms in early PD patients as well as motor fluctuations in the advanced stages of the disease.

• Treatment with dopamine agonists can be complicated by peripheral (nausea, vomiting, orthostatic hypotension, oedema), and central (hallucinations, psychosis, impulsive compulsive behaviors) adverse effects.

• Impulse Control Disorder (ICD), Dopamine agonists Withdrawal Syndrome (DAWS) and heart failure emerged as class-related side effects during the post-marketing phase.

• NEDA adverse events have a multifactorial genesis and derived from the interaction between genetic susceptibility, the neurobiological changes that accompanying PD, general health conditions, and the dopamine replacement therapy.

• A tailor-made approach based on patients’ physical, cognitive and behavioural characteristics is crucial to optimize NEDA risk-benefit ratio.

This box summarizes key points contained in the article.

Declaration of interest

M Torti provided consultation to Zambon, UCB and Chiesi Pharma. F Stocchi provided consultation to Zambon, UCB, Chiesi Pharma, Lundbeck, Sunovion, Bial, SynAgile, Biogen, Kiowa and Impax. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this manuscript is a speaker and advisor for Boehringer, Desitin, GSK and UCB. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.