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Article: Mortality in children and adolescents prescribed antipsychotic medication: A retrospective cohort study using the UK general practice research database

TitleMortality in children and adolescents prescribed antipsychotic medication: A retrospective cohort study using the UK general practice research database
Authors
KeywordsAdolescents
Antipsychotics
Children
Death
Thioridazine
Issue Date2011
PublisherAdis International Ltd. The Journal's web site is located at http://drugsafety.adisonline.com/
Citation
Drug Safety, 2011, v. 34 n. 9, p. 773-781 How to Cite?
AbstractBackground: Antipsychotic prescribing in children has risen in many countries; however, the safety of these agents in the young has not yet been fully established. Potentially fatal antipsychotic-related adverse events include cardiac complications and neuroleptic malignant syndrome. Objective: The objective of this study was to investigate mortality in children and adolescents taking antipsychotic medication. Methods: The General Practice Research Database (GPRD) was used as a data source for this study. Cases were identified from a cohort of patients previously studied. The study population encompassed all patients aged >18 years and under who received at least one prescription for an antipsychotic from 1 January 1992 to 31 December 2005. Patients were followed from the date of the first antipsychotic drug prescription until the earliest occurrence of a code of death, age 18 years or the end of the study period. Cases of death were identified by screening patients' medical records for clinical or referral events with events indicating death, or if a transferred-out patient has a 'transfer out reason' specified as 'death'. Confirmation of cases was carried out by examining individual patient profiles and from questionnaires sent to GPs. If necessary, the death certificates and/or post mortem reports were obtained by the source data verification service the GPRD provide. Once cases of death were identified, crude mortality rate (CMR) and standardized mortality ratio (SMR) were calculated. Baseline mortality rates were obtained from the Office for National Statistics. A modified WHO causality assessment was conducted to determine the likelihood of a relationship between the drug and an event of death. Results: The cohort contained 2767 patients who received at least one antipsychotic prescription. There were 30 deceased cases in the cohort. The GP questionnaire response rate was 97%. Of the 30 cases, 24 were related to preexisting medical conditions, including neoplastic diseases and HIV. After excluding these patients, six cases of death from 5963 person-years and 1958 treatment-years remained. The median age of death was 17 years (interquartile range 14-17.75). The overall CMR was 1.01 per 1000 person-years at risk (95% CI 0.20, 1.81) and SMR was 4.03 (95% CI 1.48, 8.76). Of the six cases, only one was deemed possibly associated with antipsychotic therapy, based on the causality assessment analysis conducted; CMR based on this case was 0.51 per 1000 treatment-years (95% CI 0.09, 2.89). The remaining five cases of death were unlikely to be associated with antipsychotic therapy. Conclusions: Our study demonstrated an elevated SMR in patients exposed to antipsychotics. However, the elevated SMR was unlikely caused by antipsychotic treatment, but would suggest the possibility of inadequate management or poor control of patients' underlying medical conditions prior to death. © 2011 Adis Data Information BV. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/171427
ISSN
2023 Impact Factor: 4.0
2023 SCImago Journal Rankings: 1.204
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRani, FAen_US
dc.contributor.authorByrne, Pen_US
dc.contributor.authorCranswick, Nen_US
dc.contributor.authorMurray, MLen_US
dc.contributor.authorWong, ICKen_US
dc.date.accessioned2012-10-30T06:14:07Z-
dc.date.available2012-10-30T06:14:07Z-
dc.date.issued2011en_US
dc.identifier.citationDrug Safety, 2011, v. 34 n. 9, p. 773-781en_US
dc.identifier.issn0114-5916en_US
dc.identifier.urihttp://hdl.handle.net/10722/171427-
dc.description.abstractBackground: Antipsychotic prescribing in children has risen in many countries; however, the safety of these agents in the young has not yet been fully established. Potentially fatal antipsychotic-related adverse events include cardiac complications and neuroleptic malignant syndrome. Objective: The objective of this study was to investigate mortality in children and adolescents taking antipsychotic medication. Methods: The General Practice Research Database (GPRD) was used as a data source for this study. Cases were identified from a cohort of patients previously studied. The study population encompassed all patients aged >18 years and under who received at least one prescription for an antipsychotic from 1 January 1992 to 31 December 2005. Patients were followed from the date of the first antipsychotic drug prescription until the earliest occurrence of a code of death, age 18 years or the end of the study period. Cases of death were identified by screening patients' medical records for clinical or referral events with events indicating death, or if a transferred-out patient has a 'transfer out reason' specified as 'death'. Confirmation of cases was carried out by examining individual patient profiles and from questionnaires sent to GPs. If necessary, the death certificates and/or post mortem reports were obtained by the source data verification service the GPRD provide. Once cases of death were identified, crude mortality rate (CMR) and standardized mortality ratio (SMR) were calculated. Baseline mortality rates were obtained from the Office for National Statistics. A modified WHO causality assessment was conducted to determine the likelihood of a relationship between the drug and an event of death. Results: The cohort contained 2767 patients who received at least one antipsychotic prescription. There were 30 deceased cases in the cohort. The GP questionnaire response rate was 97%. Of the 30 cases, 24 were related to preexisting medical conditions, including neoplastic diseases and HIV. After excluding these patients, six cases of death from 5963 person-years and 1958 treatment-years remained. The median age of death was 17 years (interquartile range 14-17.75). The overall CMR was 1.01 per 1000 person-years at risk (95% CI 0.20, 1.81) and SMR was 4.03 (95% CI 1.48, 8.76). Of the six cases, only one was deemed possibly associated with antipsychotic therapy, based on the causality assessment analysis conducted; CMR based on this case was 0.51 per 1000 treatment-years (95% CI 0.09, 2.89). The remaining five cases of death were unlikely to be associated with antipsychotic therapy. Conclusions: Our study demonstrated an elevated SMR in patients exposed to antipsychotics. However, the elevated SMR was unlikely caused by antipsychotic treatment, but would suggest the possibility of inadequate management or poor control of patients' underlying medical conditions prior to death. © 2011 Adis Data Information BV. All rights reserved.en_US
dc.languageengen_US
dc.publisherAdis International Ltd. The Journal's web site is located at http://drugsafety.adisonline.com/en_US
dc.relation.ispartofDrug Safetyen_US
dc.subjectAdolescents-
dc.subjectAntipsychotics-
dc.subjectChildren-
dc.subjectDeath-
dc.subjectThioridazine-
dc.subject.meshAdolescenten_US
dc.subject.meshAntipsychotic Agents - Adverse Effectsen_US
dc.subject.meshChilden_US
dc.subject.meshCohort Studiesen_US
dc.subject.meshDatabases, Factualen_US
dc.subject.meshDrug Utilizationen_US
dc.subject.meshFemaleen_US
dc.subject.meshGreat Britainen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMortalityen_US
dc.subject.meshRetrospective Studiesen_US
dc.titleMortality in children and adolescents prescribed antipsychotic medication: A retrospective cohort study using the UK general practice research databaseen_US
dc.typeArticleen_US
dc.identifier.emailWong, ICK:wongick@hku.hken_US
dc.identifier.authorityWong, ICK=rp01480en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.2165/11591120-000000000-00000en_US
dc.identifier.pmid21830839-
dc.identifier.scopuseid_2-s2.0-80051584564en_US
dc.identifier.hkuros207205-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80051584564&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume34en_US
dc.identifier.issue9en_US
dc.identifier.spage773en_US
dc.identifier.epage781en_US
dc.identifier.isiWOS:000294528900005-
dc.publisher.placeNew Zealanden_US
dc.identifier.scopusauthoridRani, FA=24336008200en_US
dc.identifier.scopusauthoridByrne, P=36149774000en_US
dc.identifier.scopusauthoridCranswick, N=6601977827en_US
dc.identifier.scopusauthoridMurray, ML=7403583537en_US
dc.identifier.scopusauthoridWong, ICK=7102513915en_US
dc.identifier.issnl0114-5916-

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