Document Detail


Serum concentrations of haloperidol pyridinium metabolites and the relationship with tardive dyskinesia and parkinsonism: a cross-section study in psychiatric patients.
MedLine Citation:
PMID:  16025420     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: The objective of this study was to provide more clinical data of the potential neurotoxic metabolite haloperidol pyridinium (HP+) in psychiatric patients during long-term treatment with haloperidol and to investigate a possible relationship with extrapyramidal adverse effects. METHODS: Serum concentrations of HP+, reduced haloperidol pyridinium (RHP+), haloperidol (H), and reduced haloperidol (RH) were measured for 41 psychiatric patients of a nursing residence (27 females, 14 males, 34-79 years of age). Severity of tardive dyskinesia (TD) and parkinsonism were rated with the Tardive Dyskinesia Rating Scale (TDRS) and Extrapyramidal Symptom Rating Scale (EPS), respectively. In addition, several patient- and treatment-related variables were investigated, for example cumulative dose (Dcum) of haloperidol. RESULTS: Serum concentration were 0.69 microg/L (0-1.53) for HP+ and 0.41 microg/L (0-1.50) for RHP+ with ratios HP+/H of 0.072 (0.017-0.18) and RHP+/RH of 0.094 (0-0.36) at doses of 10.6 mg/day (3.6-30) [mean (range) in each case]. Multiple regression revealed decreased clearance of HP+ with age. One third of patients with more severe TD (TDRS > or = 10, n = 14) had an increased relative body burden of HP+ and H, as calculated by HP+/H * Dcum of haloperidol than patients with less severe or no TD (TDRS < 10, n = 27), i. e. 5.8 g (2.0-11.9) and 3.3 g (0-9.5), respectively [mean (range), p = 0.005, U test]. Patients with mild to severe parkinsonism (EPS > 0.3, n = 16) had a significantly higher aromatization ratio HP+/H than patients with no or minimal parkinsonism (EPS < or = 0.3, n = 25), i. e. 0.14 (0.04-0.36) and 0.06 (0-0.16), respectively [mean (range), p = 0.003, U test]. CONCLUSION: In psychiatric patients treated with haloperidol for the long-term, the severity of TD and parkinsonism is associated with an increased ratio HP+/H. This is explained by the neurotoxicity of HP+ according to the pyridinium hypothesis.
Authors:
S Ulrich; U Sandmann; A Genz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacopsychiatry     Volume:  38     ISSN:  0176-3679     ISO Abbreviation:  Pharmacopsychiatry     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-18     Completed Date:  2005-08-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8402938     Medline TA:  Pharmacopsychiatry     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  171-7     Citation Subset:  IM    
Affiliation:
Institute of Clinical Pharmacology, University Hospital, Otto-von-Guericke University, Magdeburg, Germany. SUlrichMagdeburg@aol.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Analysis of Variance
Antipsychotic Agents / blood*,  therapeutic use
Chromatography, High Pressure Liquid
Cross-Sectional Studies
Dose-Response Relationship, Drug
Dyskinesia, Drug-Induced / blood*,  epidemiology
Female
Haloperidol / blood*,  therapeutic use
Humans
Linear Models
Male
Middle Aged
Parkinson Disease, Secondary / blood*,  epidemiology
Psychotic Disorders / blood,  complications*,  drug therapy
Pyridinium Compounds / blood*
Retrospective Studies
Spectrometry, Fluorescence
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 0/Pyridinium Compounds; 52-86-8/Haloperidol

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