Comparison of Olanzapine and Risperidone in the Treatment of Psychosis and Associated Behavioral Disturbances in Patients With Dementia

Deberdt, Walter; Dysken, Maurice W.; Rappaport, Stephen A.; Feldman, Peter D.; Young, C.A.; Hay, Donald P.; Lehman, Deborah; Dossenbach, M.; Degenhardt, Elisabeth K.; Breier, Alan

doi:10.1097/00019442-200508000-00012

Cited by 103 publications

(96 citation statements)

References 30 publications

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“…Virtually all studies to date have considered only presence or absence of psychosis. However, when we alternatively considered two more restrictive thresholds of clinically significant psychosis from the NPIFthat have been used as criteria for entry into clinical trials of antipsychotic drugs (Street et al, 2000;Deberdt et al, 2005) F we found essentially the same results. These analyses suggest that our findings did not depend heavily on the criterion employed to classify AD subjects as psychotic.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 58%

“…When psychosis was alternatively defined by a score X3 on either the Delusions or Hallucinations item of the NPI (Street et al, 2000), the presence of e4 was still associated with psychosis (OR ¼ 2.10, 95% CI ¼ 1.11-3.99, P ¼ 0.020). When psychosis was instead defined by NPI-Psychosis score X6 (Deberdt et al, 2005), the presence of e4 was significantly associated with psychosis (OR ¼ 2.45, 95% CI ¼ 1.21-4.98, P ¼ 0.013).…”

Section: Discussionmentioning

confidence: 99%

“…To ascertain whether our results were dependent on a particular definition of psychosis, we repeated the multiple logistic regression analysis using two progressively more restrictive criteria that have been utilized for entry into trials of antipsychotic drug for patients with dementia: (1) score X3 on either the Delusions or Hallucinations item of the NPI, corresponding with moderate severity or frequency (Street et al, 2000); (2) NPI-Psychosis X6 (Deberdt et al, 2005). We also examined the effect of four concomitant medication classes on psychotic symptoms by simultaneously adding them as independent variables to the primary logistic regression analysis.…”

Section: Discussionmentioning

confidence: 99%

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Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Zdanys

Kleiman

MacAvoy

et al. 2006

Neuropsychopharmacol

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The apolipoprotein E (ApoE) e4 allele is a well-documented genetic risk factor for sporadic Alzheimer's disease (AD). Its association with psychopathology among AD patients has been the subject of discrepant reports. We aimed to determine whether ApoE e4 + and e4-AD patients exhibit a different risk profile for psychotic symptoms and other behavioral disturbances. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity of psychotic and other behavioral symptoms in a sample of n ¼ 266 AD patients who had been genotyped for ApoE. Multiple logistic regression models were used to calculate the association between the ApoE e4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on e4 effects and to examine the association between e4 and other behavioral symptoms. ApoE e4 was significantly associated with psychotic symptoms (odds ratio (OR) ¼ 1.87, 95% CI ¼ 1.07-3.29, P ¼ 0.029), adjusting for age, sex, education, and MMSE score. More stringent definitions of clinically significant psychosis yielded similar results. Exploratory analyses suggested that this effect accrued specifically from patients with severe-stage AD and primarily from an association between e4 and delusions. The e4 allele did not appear to influence the development of most other behavioral symptoms in our sample. In conclusion, AD patients who carry the ApoE e4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.

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Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Zdanys

Kleiman

MacAvoy

et al. 2006

Neuropsychopharmacol

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“…Foram identificados nove ECR controlados com placebo, sendo quatro estudos com risperidona (De Deyn et al, 1999;Katz et al, 1999;Brodaty et al, 2003;Mintzer et al, 2006), dois com olanzapina (Street et al, 2000;De Deyn et al, 2004), um com risperidona e olanzapina (Debert et al, 2005), um com quetiapina (Ballard et al, 2005) e um com aripiprazol (De Deyn et al, 2005). Todos os ECR identificados foram incluídos nas metanálises, e suas características estão descritas na Tabela 1.…”

Section: Resultsunclassified

Eficácia e segurança dos antipsicóticos atípicos nas demências: uma revisão sistemática

Ramos¹,

Rocha²

2006

J. bras. psiquiatr.

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ResumoObjetivo: O emprego de antipsicóticos atípicos (AA) no tratamento de sintomas psicológicos e comportamentais das demências (SPCD) tem sido alvo de discussão em relação à eficácia e à segurança. O objetivo deste artigo é propiciar atualização sobre o tema. Métodos: Revisão da literatura publicada nos últimos dez anos com ênfase em metanálises e ensaios clínicos randomizados (ECR) controlados com placebo. Resultados: Três metanálises e nove ensaios clínicos foram analisados. Há evidências de eficácia clínica para risperidona (1mg/dia), olanzapina (5 a 10mg/dia) e aripiprazol (2 a 15mg/dia) no tratamento de agressividade e/ou SPCD em geral, e para risperidona (1mg/dia) no tratamento de sintomas psicóticos associados à demência. Os eventos adversos comuns com o uso de AA foram sonolência, sintomas extrapiramidais (SEP), incontinência ou infecção do trato urinário e alterações de marcha. O tratamento com AA associou-se a maior risco de eventos cerebrovasculares e de mortalidade em idosos com demência. Conclusão: Baixas dosagens de risperidona, olanzapina e aripiprazol são eficazes na redução de agressividade e/ou SPCD globais; risperidona é eficaz na redução de sintomas psicóticos associados à demência. Em virtude de esses tratamentos associarem-se a pequeno aumento no risco de eventos cerebrovasculares e mortalidade, seu uso deve ser reservado para sintomatologia moderada/grave. Palavras-chave: demência, antipsicóticos atípicos, sintomas neuropsiquiátricos. AbstractObjective: Concerns have been raised about efficacy and adverse events of atypical antipsychotics in the treatment of behavioural and psychological symptoms of dementia (BPSD). This paper is an update on current evidence of this theme. Methods: Review of published meta-analysis and randomized placebo-controlled trials (RCTs) in the last ten years. Results: Three meta-analysis and nine RCTs were evaluated. Evidence suggests that risperidone (1mg/day), olanzapine (5 to 10mg/day), and aripiprazole (2 to 15mg/day) are effective in treating aggression and/or BPSD overall; risperidone (1mg/day) reduces psychosis. Adverse events were mainly somnolence, extrapyramidal symptoms, urinary tract infection or incontinence, and abnormal gait with drug treatment. Atypical antipsychotics were associated with increased risk for cerebrovascular adverse events and mortality in elderly patients with dementia. Conclusion: Low doses of risperidone, olanzapine, and aripiprazole are effective in treating aggression and/or BPSD overall, and risperidone reduces psychosis associated with dementia. In view of the increased risk of cerebrovascular adverse events and mortality, the use of atypical antipsychotics in individuals with dementia should be reserved for patients with moderate/severe behavioural symptoms.

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“…Ello ha llevado a algunos autores a dudar de la eficacia de los neurolépticos atípicos, e incluso, a no recomendar su uso en estos pacientes (1,3,12,14). En efecto, en los ancianos en general y en los pacientes con demencia en particular, este grupo farmacológico puede tener unas consecuencias adversas muy importantes: caídas, trastornos en la marcha, deterioro del estado cognitivo, alteraciones cardiacas, delirium etc.…”

unclassified

Antipsicóticos atípicos:¿héroes o villanos?: Una perspectiva clínica

Álvarez-Fernández

2007

An. Med. Interna (Madrid)

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En los últimos años se ha puesto de manifiesto la necesidad de reevaluar el papel de los neurolépticos atípicos en el tratamiento de los trastornos conductuales en los pacientes con demencia (1-5). A lo largo de este artículo, hacemos algunas reflexiones sobre el cambio de papel de este grupo farmacológico desde un prisma eminentemente clínico. ¿Son los neurolépticos atípicos los héroes en el tratamiento de los síntomas conductuales en las demencias?Hasta hace muy poco, la recomendación de los grupos de expertos era el empleo de estos fármacos en los estados de agitación y agresividad (6). El esquema terapéutico en el que se adjudica a la agitación el tratamiento farmacológico con neurolépticos es muy discutible, ya que otorgar a un síntoma conductual un determinado tratamiento es dar la consideración de entidad clínica a dicho síntoma, algo poco justificado tanto desde un punto de vista empírico(no existen suficientes evidencias para esta afirmación) como fisiopatológico. En efecto, un episodio de agitación o agresividad puede estar ocasionado por un deliro de robo por ejemplo; pero también por una fobia secundaria a un cuadro de ansiedad, donde el paciente puede negarse al aseo o a los cuidados en general, lo que puede ocasionar un cuadro de agitación y agresividad importante que puede persistir durante todo el día y no sólo cuando intentamos realizar estos cuidados. En ambos casos, el trastorno conductual es el mismo, la agitación con agresividad o sin ella; aunque en el primero, el uso de neurolépticos puede ser el fármaco conceptualmente más indicado para controlar el cuadro, y en el segundo, serán los ansiolíticos los que jueguen su papel. En este sentido, sorprende que en un número sustancial de los ensayos clínicos (teniendo en cuenta su escaso número) la mayoría de los pacientes que se incluyen tienen trastornos conductuales pero no psicóticos, lo que genera mayor incertidumbre a la hora de adjudicar a estos pacientes un tratamiento neuroléptico (7,8).Aunque no es frecuente a la hora de presentar los resultados distinguir entre los efectos sobre la agitación y sobre la psicosis, en el trabajo de Katz y cols. (9) se observa que la dosis de 2 mg es significativamente más efectiva que la dosis de 1mg a la hora de reducir la puntuación global en la escala BEHAVE-AD; sin embargo, cuando analizan el efecto sobre la psicosis, es la dosis de 1mg la que resulta ser significativa frente al grupo placebo. Del mismo modo, al analizar los datos excluyendo los pacientes que han sufrido somnolencia o síntomas extrapiraidales (EPS), la efectividad es más significativa a esta dosis. ¿Cómo podemos interpretar este dato? Probablemente se deba a que, si incluimos a pacientes con y sin síntomas psicóticos en el mismo análisis, necesitaremos más dosis de neuroléptico para que resulte significativo. El grupo de pacientes agitados sin una causa psicótica necesitará más neuroléptico para su control, ya que éste se produce más por efecto secundario que por efecto terapéutico. En el ensayo clínico de Street y cols. (10), cuando a...

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Comparison of Olanzapine and Risperidone in the Treatment of Psychosis and Associated Behavioral Disturbances in Patients With Dementia

Cited by 103 publications

References 30 publications

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Eficácia e segurança dos antipsicóticos atípicos nas demências: uma revisão sistemática

Antipsicóticos atípicos:¿héroes o villanos?: Una perspectiva clínica

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