Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions.

Despite accumulating evidence pointing to a genetic basis for tardive dyskinesia, results to date have been inconsistent owing to limited statistical power and limitations in molecular genetic methodology. A Medline, EMBASE and PsychINFO search for literature published between 1976 and June 2007 was performed, yielding 20 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. Evidence from pooled data for genetic association with tardive dyskinesia (TD) showed (1) in COMT(val158met), using Val-Val homozygotes as reference category, a protective effect for Val-Met heterozygotes (OR=0.63, 95% CI: 0.46-0.86, P=0.004) and Met carriers (OR=0.66, 95% CI: 0.49-0.88, P=0.005); (2) in Taq1A in DRD2, using the A1 variant as reference category, a risk-increasing effect for the A2 variant (OR=1.30, 95% CI: 1.03-1.65, P=0.026), and A2-A2 homozygotes using A1-A1 as reference category (OR=1.80, 95% CI: 1.03-3.15, P=0.037); (3) in MnSOD Ala-9Val, using Ala-Ala homozygotes as reference category, a protective effect for Ala-Val (OR=0.37, 95% CI: 0.17-0.79, P=0.009) and for Val carriers (OR=0.49, 95% CI: 0.24-1.00, P=0.047). These analyses suggest multiple genetic influences on TD, indicative of pharmacogenetic interactions. Although associations are small, the effects underlying them may be subject to interactions with other loci that, when identified, may have acceptable predictive power. Future genetic research will take advantage of new genomic knowledge. Molecular Psychiatry (2008) 13, 544-556; doi:10.1038/sj.mp.4002142; published online 8 January 2008.

Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics-a European study.

OBJECTIVE: The aim of this study was to investigate to what extent atypical antipsychotics, conventional antipsychotics and anticholinergics are prescribed simultaneously in daily clinical practice in Europe. METHOD: A pharmaco-epidemiological study was carried out in which hospital pharmacists from 45 hospitals in Belgium, Denmark, France, Germany, The Netherlands and Scotland participated. Prescription data for 2,725 patients (mainly inpatients) who had been using an atypical antipsychotic for more than 6 weeks were analysed. MAIN OUTCOME MEASURE: The frequencies of simultaneous prescription of atypical antipsychotics with other antipsychotics and/or anticholinergics. RESULTS: In this sample of patients with an atypical antipsychotic 42.1% was prescribed another antipsychotic (24.1% if low-potent antipsychotics were not included in the analysis) and 30.1% was prescribed an anticholinergic. In total 47.1% of patients were prescribed an atypical antipsychotic without any other antipsychotic or anticholinergic. CONCLUSION: It is common practice to prescribe a combination of atypical antipsychotics and conventional antipsychotics and/or anticholinergics. This suggests that monotherapy involving an atypical antipsychotic is not considered to be an adequate treatment for a substantial number of patients in clinical practice.

[Malignant neuroleptic syndrome: complete anticoagulant treatment or not?]. / Het maligne neurolepticasyndroom: wel of geen volledige antistollingsbehandeling?

A case is reported, in which fatal pulmonary embolism complicated the course of a neuroleptic malignant syndrome (NMS). This syndrome includes several risk factors for the development of venous thromboembolism, such as: protracted immobility; severe rigidity causing a slowing of blood flow through the deep venous system; hypovolaemia with increased blood viscosity and activation of coagulation by rhabdomyolysis. An analysis of 115 case reports in the literature on NMS showed that 3 out of 13 patients with fatal NMS (23%) died of pulmonary embolism. The reviewed case, the literature findings and the risk factors mentioned cause us to believe that complete anticoagulant therapy may have a place in the therapeutic approach to patients with NMS.

[Tardive dystonia]. / Tardieve dystonie.

Two patients with tardive dystonia are presented. Tardive dystonia is a late-onset side effect of dopamine antagonist, which occurs in approximately 2% of the patients in the course of treatment with neuroleptic medication. The dystonia usually starts by affecting the musculature of face and (or) neck and is often progressive to a segmental localization. Of differential diagnostic importance are: conversion disorder, acute dystonia, Wilson's disease, idiopathic dystonia and dystonia triggered by other agents. Treatment starts with reevaluation of the need for ongoing neuroleptic treatment. Investigation of the pharmacotherapy of the dystonia concerns mostly treatment with dopamine depletors or with high doses of anticholinergic agents. Improvement of 50% of the patients is reported, although total recovery is rare. Many other substances and also some physical methods (ECT and surgery) have been used with varying results.