Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

Arbouw, Maurits E. L.; Vugt, Jeroen P. P. van; Egberts, Toine C. G.; Guchelaar, Henk‐Jan

doi:10.2217/14622416.8.2.159

Cited by 19 publications

(13 citation statements)

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“…Summarizing the main results, positive associations were found between the occurrence of LID and polymorphisms in the dopamine For reprint orders, please contact: reprints@futuremedicine.com future science group Editorial Arbouw, Guchelaar & Egberts reveal significant associations between neurotransmitter receptors and transporter genotypes and therapy response or side effects [6,13]. In addition, associations found in one study could not be replicated in other studies.…”

Section: "A Large Interindividual Variability In Drug Response Hasmentioning

confidence: 94%

“…Motor fluctuations have been associated with a DRD2 gene polymorphism [6], although other studies could not replicate this finding. Conflicting results have been reported concerning the relationship between the occurrence of drug-induced hallucinations in PD and genetic polymorphisms.…”

mentioning

confidence: 88%

“…In 2007, we reviewed the literature concerning the pharmacogenetics of anti-PD drugs [6]. Some interesting associations between genetic variants and response to anti-PD drugs were reported; however, these were conflicting.…”

Section: "A Large Interindividual Variability In Drug Response Hasmentioning

confidence: 99%

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Novel Insights in Pharmacogenetics of Drug Response in Parkinson‘s Disease

2010

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Novel insights in pharmacogenetics of drug response in Parkinson's disease receptor DRD2 gene, the dopamine transporter (DAT ) gene and µ1 opioid receptor (OPRM1) gene. Motor fluctuations have been associated with a DRD2 gene polymorphism [6], although other studies could not replicate this finding. Conflicting results have been reported concerning the relationship between the occurrence of drug-induced hallucinations in PD and genetic polymorphisms. While some studies demonstrated significant associations between hallucinations and polymorphisms in the DAT gene, the cholecystokinin (CCK ) gene and the apolipoprotein E (APOE) gene, others failed to replicate these results. Associations were found between sleep attacks without warning signs and a polymorphism in the DRD4 gene, the preprohypocretin (HCRT ) gene, the DRD2 gene and the catechol-O-methyl transferase (COMT ) gene. In addition, similar findings were found in recent studies investigating polymorphisms in genes encoding dopamine D 2 and D 3 receptors [7][8][9] and COMT [10]. Lin and colleagues investigated the role of angiotensin I-converting enzyme in levodopa response [11]. They demonstrated that patients with a homozygote (ins/ins) genotype of the ACE gene had a 2.5-times higher risk of levodopa-induced psychosis, a disabling complication, particularly in the later stage of the disease. The role of angiotensin I-converting enzyme in the development of levodopa-induced psychosis is relatively unexplored. It is necessary to reproduce this study in independent cohorts.We concluded that, in comparison with other subject areas such as psychiatry [12], relatively few efforts have been made to investigate the role of pharmacogenetics in the individual response to anti-PD drugs. The focus of pharmacogenetic studies in patients with PD was mainly on genes coding for drug receptors, drug transporters and synaptic drug-metabolizing enzymes (pharmacodynamics). The pharmacogenetic studies in both PD and psychiatry did not, for the most part, Parkinson's disease (PD) is characterized by brady kinesia, rigidity and tremor, and is the result of degeneration of dopaminergic neurones in the substantia nigra pars compacta. PD has a prevalence of approximately 0.5-1% in persons of 65-69 years, rising to 1-3% among persons of 80 years and older [1]. Twin studies suggest a limited role for genetic factors in the etiology of PD, perhaps most prominently in early-onset forms [2]. The etiology of the common late-onset forms of PD remains largely to be elucidated.Anti-PD drugs, such as levodopa and the direct-acting dopamine agonists, are effective in reducing the motor symptoms of PD. However, these drugs are also associated with the development of motor complications, such as levodopainduced dyskinesia (LID), response fluctuations and side effects, such as hallucinations and excessive daytime sleepiness. In clinical practice, a large interindividual variability in drug response has been noticed. For example, up to 45% of levodopa users develop LID within 5 years, while others...

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Section: "A Large Interindividual Variability In Drug Response Hasmentioning

confidence: 94%

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confidence: 88%

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Novel Insights in Pharmacogenetics of Drug Response in Parkinson‘s Disease

2010

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“…Genetic polymorphisms affecting dopaminergic medication metabolism may influence PD-related motor complications such as dyskinesias or fluctuations 86, 87 . With the growth of pharmacogenetics, inter-individual differences in medication responses due to genetic polymorphisms may become increasingly important in drug development, evaluation of drug efficacy and toxicity, and individualized patient care.…”

Section: Novel Methods For Studying Pd Psychosismentioning

confidence: 99%

An update expert opinion on management and research strategies in Parkinson's disease psychosis

Goldman

Vaughan

Goetz

2011

Expert Opinion on Pharmacotherapy

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Introduction Psychosis, a frequent complication in Parkinson’s disease (PD), contributes significantly to morbidity, mortality, nursing home placement, and quality of life. Medication side effects, issues of trial design, and negative outcomes have limited clinical advances of new treatments for PD psychosis. Evidence-based medicine maintains clozapine as the most effective antipsychotic in PD without motor worsening, despite risk of agranulocytosis. Safe, effective treatments that improve psychosis without exacerbating parkinsonism are greatly needed. Areas covered This article reviews: 1) the phenomenology of PD psychosis, 2) pharmacological rationale for antipsychotics in PD, 3) clinical trials of antipsychotics in PD, 4) novel research strategies such as neuroimaging, genetics, and animal models, and 5) associated challenges in studying and treating PD psychosis. Preparation of this review included an extensive literature search using PubMed. Expert Opinion Management of PD psychosis is complex. Challenges pertaining to study design, rating scales, subject recruitment, and completion have limited PD psychosis treatment trials. Novel research strategies focus on non-dopaminergic systems and incorporate neuroimaging, genetic associations, and animal models. These strategies also have challenges but have the potential to enhance our understanding of PD psychosis and advance the development of agents that can ultimately be tested in well-designed, randomized, controlled trials.

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“…Genetic polymorphisms that affect levodopa or dopamine-agonist metabolism have been shown to play a role in other medication-related complications such as dyskinesias or motor fluctuations [73, 74]. With the growing field of pharmacogenetics, interindividual differences in medication responses due to underlying genetic polymorphisms may become increasingly important in drug development, evaluation of drug efficacy and toxicity, and ultimately, individualized patient care.…”

Section: Genetic Risk Factors For Pd Psychosismentioning

confidence: 99%

New Thoughts on Thought Disorders in Parkinson's Disease: Review of Current Research Strategies and Challenges

Goldman

2011

Parkinson's Disease

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Psychosis is a frequent nonmotor complication in Parkinson's disease (PD), characterized by a broad phenomenology and likely due to a variety of intrinsic (i.e., PD-related) and extrinsic factors. Safe and effective therapies are greatly needed as PD psychosis contributes significantly to morbidity, mortality, nursing home placement, and quality of life. Novel research strategies focused on understanding the pharmacology and pathophysiology of PD psychosis, utilizing translational research including animal models, genetics, and neuroimaging, and even looking beyond the dopamine system may further therapeutic advances. This review discusses new research strategies regarding the neurobiology and treatment of PD psychosis and several associated challenges.

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Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

Cited by 19 publications

References 82 publications

Novel Insights in Pharmacogenetics of Drug Response in Parkinson‘s Disease

Novel Insights in Pharmacogenetics of Drug Response in Parkinson‘s Disease

An update expert opinion on management and research strategies in Parkinson's disease psychosis

New Thoughts on Thought Disorders in Parkinson's Disease: Review of Current Research Strategies and Challenges

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