Potential Causes of Higher Mortality in Elderly Users of Conventional and Atypical Antipsychotic Medications
ABSTRACT To investigate the potential mechanisms through which conventional antipsychotic medication (APM) might act, the specific causes of death in elderly patients newly started on conventional APM were compared with those of patients taking atypical APM.
All British Columbia residents aged 65 and older who initiated a conventional or atypical APM between 1996 and 2004.
Cox proportional hazards models were used to compare risks of developing a specific cause of death within 180 days of APM initiation. Potential confounders were adjusted for using traditional multivariable, propensity-score, and instrumental-variable adjustments.
The study cohort included 12,882 initiators of conventional APM and 24,359 initiators of atypical APM. Of 3,821 total deaths within the first 180 day of use, cardiovascular (CV) deaths accounted for 49% of deaths. Initiators of conventional APM had a significantly higher adjusted risk of all CV death (hazard ratio (HR)=1.23, 95% confidence interval (CI)=1.10-1.36) and out-of-hospital CV death (HR=1.36, 95% CI=1.19-1.56) than initiators of atypical APM. Initiators of conventional APM also had a higher risk of death due to respiratory diseases, nervous system diseases, and other causes.
These data suggest that greater risk of CV deaths might explain approximately half of the excess mortality in initiators of conventional APM. The risk of death due to respiratory causes was also significantly higher in conventional APM use.
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ABSTRACT: Doelstelling: Hoewel antipsychotica veel worden voorgeschreven bij behandeling van gedragsproblemen bij dementie, zijn onderzoeken naar het beloop van deze symptomen in verpleeghuizen schaars. Onze primaire doelstelling is het beloop van gedragsproblemen te beschrijven tijdens de behandeling met antipsychotica in een grote steekproef van oudere verpleeghuispatiënten met dementie. Methoden: Het beloop van gedragsproblemen tijdens de behandeling met antipsychotica werd bestudeerd door het vergelijken van de kenmerken van de patiënten voor, tijdens en na de behandeling met antipsychotica. De studie werd uitgevoerd met behulp van de VURAIDB, een database met meer dan 40.000 beoordelingen van meer dan 10.000 verpleeghuisbewoners in Nederland. We gebruikten de challenging behaviour profile (CBP) als maat voor het probleemgedrag. Resultaten: In totaal werden 556 patiënten die met antipsychotica begonnen, onderzocht. Van deze verbeterden 101 (18,2%) en verslechterden 260 patiënten (46,8%) na 3 maanden op de gedragscore, vergeleken met hun scores voor de therapie (z = −7,96, p < 0,0001). Patiënten met ernstig uitdagend gedrag lieten vaker verbetering zien dan patiënten met milde stoornissen. Het beloop van gedragsproblemen na het staken van het antipsychoticagebruik werd geëvalueerd bij 520 patiënten. Van deze patiënten bleven 352 (68%) stabiel of verbeterden na 3 maanden in vergelijking met hun scores vóór het staken (z = −0,70, p = 0,486), dit cijfer was 6 maanden na staken 58% (z = −2,77, p = 0,006). Conclusie: Tijdens de behandeling van verpleeghuisbewoners met dementie met antipsychotica neemt de ernst van de meeste gedragsproblemen toe bij de meeste patiënten. Bij slechts een op de zes patiënten is er een verbetering. Na het staken van antipsychotica bleven de gedragsproblemen stabiel of verbeterden in 58% van de patiënten. Background: Although antipsychotic treatment of behavioral problems in dementia is common, studies investigating the course of these symptoms in nursing homes are scarce. Our primary objective is therefore to describe the course of behavioral problems during antipsychotic treatment in a large sample of elderly nursing home patients with dementia. Methods: The course of behavioral problems during antipsychotic treatment was studied by comparing the characteristics of patients before, during and after antipsychotic treatment. The study was conducted using the VURAIDB, a database with over 40,000 assessments of over 10,000 nursing home residents in the Netherlands. We used the Challenging Behavior Profile (CBP) to measure an overall behavior score. Results: In total, 556 patients starting with antipsychotics were studied. Of these, 101 (18.2%) improved and 260 (46.8%) deteriorated at three months on the behavior score, compared with their scores before therapy (z = −7.955; p<0.0001). Patients with severe challenging behavior showed improvement more often than patients with mild disturbances. The course of behavioral symptoms after withdrawal was evaluated in 520 patients. Of these patients, 352 (68%) remained stable or improved at 3 months compared with their scores before withdrawal (z = −0.697; p = 0.486), this figure was 58% at 6 months after withdrawal (z = −2.77; p = 0.006). Conclusions: During treatment of nursing home residents with dementia with antipsychotics the severity of most behavioral problems continues to increase in most patients, with only one out of six patients showing improvement. After withdrawal of antipsychotics, behavioral problems remained stable or improved in 58% of patients.2010(2):70-79. DOI:10.1007/s12500-010-0031-7
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ABSTRACT: The benefits and harms of antipsychotic medication (APM) use in nursing home residents need to be examined because, although commonly used, APMs are considered an off-label use by the Food and Drug Administration for residents with dementia and behavioral problems. The objective of this study was to provide a realist literature review, summarizing original research studies on the clinical effects of conventional and atypical APM use in nursing home residents. Searches of multiple databases identified 424 potentially relevant research articles, of which 25 met the inclusion criteria. Antipsychotic medication use in nursing home residents was found to have variable efficacy when used off-label with an increased risk of many adverse events, including mortality, hip fractures, thrombotic events, cardiovascular events and hospitalizations. Findings suggested certain APM dosing regimens (e.g. fixed-dose) and shorter duration of use might have fewer adverse events. Non-pharmacological interventions should still be considered the first-line treatment option for nursing home residents with dementia related behavioral disturbances, as more studies are needed to establish safer criteria for APM use in nursing homes residents. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.Health Policy 02/2015; 119(6). DOI:10.1016/j.healthpol.2015.02.014 · 1.73 Impact Factor
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ABSTRACT: To examine the association between antipsychotic use and the risk of acute coronary syndrome (ACS) in elderly de novo users of antipsychotics. A community-based nested case-control study. Pharmacy dispensing records from community pharmacies in The Netherlands were linked to hospital discharge records of 950,000 community-dwelling residents from 1998 to 2008. Cases were 2803 patients aged 60 years or older, with a first hospital admission for ACS identified within a cohort of 26,157 elderly persons with at least one antipsychotic prescription (de novo users). For each case, four controls with no hospitalisation for ACS (n=11,024) were randomly selected from the same cohort, matched by age, gender and duration of registration in the database. Relative risks, expressed as ORs, for ACS associated with antipsychotic drug use adjusted for comorbidity. Current exposure to antipsychotics was associated with a decreased risk of hospitalisation for ACS compared with past users (adjusted OR 0.5, 95% CI 0.5 to 0.6). Cumulative use up to 100 Defined Daily Doses was also associated with a decreased risk of hospitalisation (OR 0.7, CI 0.6 to 0.8). No differences in risk were found between typical and atypical antipsychotics, current dosage or different degrees of serotonergic, histaminergic or adrenergic affinity of the antipsychotic. A decreased risk of hospitalisation for ACS in elderly patients currently using antipsychotics was found. Further research is needed to confirm our results and to determine whether there is a cardioprotective effect or a high non-referral rate in elderly antipsychotic users with ACS.Heart (British Cardiac Society) 06/2012; 98(15):1166-71. DOI:10.1136/heartjnl-2012-301801 · 6.02 Impact Factor