Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5HT2A Inverse Agonist, to Treat Impulse Control Disorders in Parkinson’s Disease.

Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5HT2A Inverse Agonist, to Treat Impulse Control Disorders in Parkinson’s Disease.

Publication date: May 13, 2019

There is no consensus on the treatment of Impulse Control Disorder (ICD) in Parkinson Disease (PD) though it is recommended to reduce the dosage of dopamine agonists (DA). Reduction of DA frequently leads to a worsening of motor signs (parkinsonism or dyskinesias due to the concomitant increase of levodopa doses) and non-motor signs with the appearance of a DA withdrawal syndrome (DAWS). Chronic stimulation of the sub-thalamic nuclei may reduce ICD but is restricted to a minority of patients and cases of new-onset ICD symptoms post stimulation have been reported. The benefit of amantadine in pathological gambling is controversial and the efficacy of clozapine has been reported in a few cases but with serious safety limitations. Very recently, naltrexone did not significantly improve ICD. Thus, an efficacious and safe treatment of ICD in PD remains an unmet need for clinical practice. Recently, it has been reported that pimavanserin, a selective serotonin 5-HT2A inverse agonist with a satisfactory safety profile without motor side effects, was efficient in improving psychosis, insomnia and day-time sleep in PD. Pimavanserin, marketed under the tradename NUPLAZID(R) was approved in 2016 by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. The link between serotonin and ICD has been well established, since the enhancement of 5HT2A receptors stimulation is associated to ICD, since serotonin modulates mesolimbic dopaminergic reward system transmission and given that serotonin neurotransmission is increased during chronic intake of dopamine agonist such as pramipexole which is well-known to induce ICD in PD patients. Thus, there is a large body of evidence suggesting that the decrease of the 5HT2A activity could be efficient in reducing ICD in PD. This further supports the concept of testing the efficacy of pimavanserin (a selective 5HT2A inverse agonist) for treating ICD in PD. Our aim is to conduct a study evaluating the efficacy and safety of pimavanserin on ICD in PD. This clinical trial is conducted with the support of the French NS-Park/FCRIN network.

Concepts Keywords
5HT2A Index php tools
Agonist Treatment hallucinations
Allergies Psychosis insomnia
Amantadine Severe depression
Anticholinergic Uncontrolled illness
Antidepressant Contraception
Antifungals Hysterectomy
Antipsychotic Chemical compounds
Artemisia Organic compounds
Azole Branches of biology
Benzodiazepine RTT
Clinical Trial Depression
Clozapine Pimavanserin
COMT Piperidines
Congestive Heart Failure Ureas
Contraception Antidepressant
Curator Dopamine agonist
CYP3A4 Antipsychotic
DA 5-HT2A receptor
DBS Php
Dementia
Depression
Dopamine Agonist
Dopamine Agonists
Dopaminergic
Dyskinesias
ECG
Echinacea
Electrolytic
FDA
France
French
Ginkgo
Hallucinations
Hypersensitivity
Hypersexuality
Hypocalcemia
Hysterectomy
Impulse
Informed Consent
Inhibitor
Insomnia
Insurance
Inverse Agonist
Levodopa
Lewy Body Dementia
Macrolides
MAOB
Medicinal Plants
Menstruation
Mesolimbic
Multiple System Atrophy
Myocardial Infarction
Naltrexone
Neurotransmission
Parkinson
Parkinsonian Syndrome
Parkinsonism
Pathological Gambling
Placebo
Pramipexole
Progressive
Psychosis
Randomization
Receptors
Renal Impairment
Reward System
Serotonin
Sleep
Strasbourg
Suicidal Thoughts
Supranuclear Palsy
Syndrome
TdP
Withdrawal Syndrome

Semantics

Type Source Name
drug DRUGBANK Pimavanserin
drug DRUGBANK Serotonin
disease MESH Impulse Control Disorders
disease DOID Impulse Control Disorder
gene UNIPROT GNPTAB
disease MESH Parkinson Disease
disease DOID Parkinson Disease
drug DRUGBANK Dopamine
disease MESH dyskinesias
drug DRUGBANK Levodopa
disease MESH syndrome
disease DOID syndrome
gene UNIPROT SLC35G1
drug DRUGBANK Amantadine
disease MESH pathological gambling
disease DOID pathological gambling
drug DRUGBANK Clozapine
drug DRUGBANK Naltrexone
gene UNIPROT HTR2A
disease MESH psychosis
disease MESH insomnia
disease MESH hallucinations
disease MESH delusions
drug DRUGBANK Pramipexole
gene UNIPROT LARGE1
gene UNIPROT CD5L
gene UNIPROT CD69
gene UNIPROT DNMT1
gene UNIPROT COMT
gene UNIPROT MAOB
drug DRUGBANK Benzodiazepine
disease MESH suffering
disease MESH multiple system atrophy
disease DOID multiple system atrophy
disease MESH progressive supranuclear palsy
disease DOID progressive supranuclear palsy
disease MESH Lewy body dementia
disease DOID Lewy body dementia
disease MESH hypersensitivity
disease DOID hypersensitivity
disease MESH Stroke
disease DOID Stroke
disease MESH myocardial infarction
disease DOID myocardial infarction
disease MESH congestive heart failure
disease DOID congestive heart failure
disease MESH long QT syndrome 5
disease DOID long QT syndrome 5
disease MESH ECG
disease MESH torsade de pointes
drug DRUGBANK Thiocolchicoside
gene UNIPROT SOX3
gene UNIPROT PHPT1
gene UNIPROT ASAH1
disease MESH hypocalcemia
gene UNIPROT CYP3A4
gene UNIPROT DOCK3
disease MESH dementia
disease DOID dementia
disease MESH depression
gene UNIPROT MCF2L
gene UNIPROT LRP2
gene UNIPROT EHD1
disease MESH cancer
disease DOID cancer
disease MESH renal
gene UNIPROT NR4A2
gene UNIPROT ALG3

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