Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study. 2004

F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
Department of Neurology, Hôpital Gabriel Montpied, Clermont-Ferrand, France. fdurif@chu-clermontferrand.fr

OBJECTIVE To investigate the efficacy and safety of clozapine in the treatment of levodopa-induced dyskinesias (LID) in patients with severe Parkinson disease (PD). METHODS Fifty patients were randomized to treatment in this 10-week, double-blind, parallel-group, placebo-controlled, multicenter trial. The principal measure of outcome was the diurnal change in the "on" time with LID assessed using a self-evaluation of the motor performance fluctuations performed every 2 weeks. An acute levodopa challenge was also performed at the beginning and end of the study. RESULTS A reduction in the duration of "on" periods with LID was noted in favor of the clozapine group at the end of the study (placebo group day 0: 4.54 +/- 0.53 hours, end: 5.28 +/- 0.70 hours; clozapine group day 0: 5.68 +/- 0.66 hours, end: 3.98 +/- 0.57 hours; p = 0.003). The mean clozapine dosage was 39.4 +/- 4.5 (SEM) mg/day. The maximal LID score at rest during the levodopa challenge was significantly decreased under clozapine treatment, with a variation from day 0 to day 70 in the placebo group of +0.15 +/- 1.01 and in the clozapine group of -2.22 +/- 0.52 (p < 0.05). Five patients receiving clozapine and seven receiving placebo discontinued on account of adverse events. Among them, three patients in the clozapine group developed eosinophilia, which rapidly resolved after withdrawal of the drug. CONCLUSIONS Clozapine is effective in the treatment of levodopa-induced dyskinesias in severe PD.

UI MeSH Term Description Entries
D007980 Levodopa The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. L-Dopa,3-Hydroxy-L-tyrosine,Dopaflex,Dopar,L-3,4-Dihydroxyphenylalanine,Larodopa,Levopa,3 Hydroxy L tyrosine,L 3,4 Dihydroxyphenylalanine,L Dopa
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010300 Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75) Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D003024 Clozapine A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Clozaril,Leponex
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D004409 Dyskinesia, Drug-Induced Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199) Dyskinesia, Medication-Induced,Medication-Induced Dyskinesia,Drug-Induced Dyskinesia,Drug-Induced Dyskinesias,Dyskinesia, Drug Induced,Dyskinesia, Medication Induced,Dyskinesias, Drug-Induced,Dyskinesias, Medication-Induced,Medication Induced Dyskinesia,Medication-Induced Dyskinesias
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000978 Antiparkinson Agents Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists. Antiparkinson Drugs,Antiparkinsonian Agents,Antiparkinsonians,Agents, Antiparkinson,Agents, Antiparkinsonian,Drugs, Antiparkinson
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes

Related Publications

F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
May 2001, Movement disorders : official journal of the Movement Disorder Society,
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
May 2007, Archives of neurology,
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
December 1987, New York state journal of medicine,
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
April 2012, Journal of clinical psychopharmacology,
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
May 2011, Journal of psychopharmacology (Oxford, England),
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
April 2012, Neurology,
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
September 2005, Archives of neurology,
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
January 2009, Clinical neuropharmacology,
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
January 2007, Movement disorders : official journal of the Movement Disorder Society,
F Durif, and B Debilly, and M Galitzky, and D Morand, and F Viallet, and M Borg, and S Thobois, and E Broussolle, and O Rascol
January 2000, Clinical neuropharmacology,
Copied contents to your clipboard!