RESUMEN
BACKGROUND: Psychotic symptoms and behavioral disturbances are a leading cause of institutionalization in elderly patients with Alzheimer's disease (AD). OBJECTIVES: Elderly nursing home patients (n=105) with possible or probable AD were entered into a multicenter study to determine the long-term efficacy and safety of olanzapine in treatment of psychotic symptoms and behavioral disturbances due to AD. METHODS: Following a double-blind, 6-week exposure to fixed-dose olanzapine (5, 10, or 15 mg/d), patients entered an additional 18-week, open-label, flexible-dose treatment. Baseline was defined from the start of the extension phase. RESULTS: Patients improved significantly on the primary efficacy measure, defined a priori, which consisted of the sum of the Agitation/Aggression, Delusions, and Hallucinations items ('Core':) of the NPI/NH. Olanzapine also significantly improved scores for the NPI/NH total and the Core item-associated Occupational Disruptiveness of the NPI/NH, as well as the BPRS total and CGI Severity-of-Alzheimer's scores. Barnes Akathasia scores improved significantly from baseline, while Simpson-Angus and AIMS scores were not significantly changed. Treatment-emergent symptoms included somnolence, accidental injury, and rash. No significant changes were seen in ECGs, including QT(c) interval, nor in weight or vital signs, including orthostasis. CONCLUSIONS: Low-dose olanzapine appears to be effective and well tolerated for treatment of behavioral disturbances and psychotic symptoms due to AD in elderly patients.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Síntomas Conductuales/tratamiento farmacológico , Pirenzepina/análogos & derivados , Pirenzepina/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Síntomas Conductuales/diagnóstico , Síntomas Conductuales/psicología , Benzodiazepinas , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Hogares para Ancianos , Humanos , Cuidados a Largo Plazo , Masculino , Pruebas Neuropsicológicas , Casas de Salud , Olanzapina , Pirenzepina/efectos adversos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/psicología , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with Alzheimer disease (AD) commonly exhibit psychosis and behavioral disturbances that impair patient functioning, create caregiver distress, and lead to institutionalization. This study was conducted to assess the efficacy and safety of olanzapine in treating psychosis and/or agitation/aggression in patients with AD. METHODS: A multicenter, double-blind, placebo-controlled, 6-week study was conducted in 206 elderly US nursing home residents with AD who exhibited psychotic and/or behavioral symptoms. Patients were randomly assigned to placebo or a fixed dose of 5, 10, or 15 mg/d of olanzapine. The primary efficacy measure was the sum of the Agitation/Aggression, Hallucinations, and Delusions items (Core Total) of the Neuropsychiatric Inventory-Nursing Home version. RESULTS: Low-dose olanzapine (5 and 10 mg/d) produced significant improvement compared with placebo on the Core Total (-7.6 vs -3.7 [P<.001] and -6.1 vs -3. 7 [P =.006], respectively). Core Total improvement with olanzapine, 15 mg/d, was not significantly greater than placebo. The Occupational Disruptiveness score, reflecting the impact of patients' psychosis and behavioral disturbances on the caregiver, was significantly reduced in the 5-mg/d olanzapine group compared with placebo (-2.7 vs -1.5; P =.008). Somnolence was significantly more common among patients receiving olanzapine (25.0%-35.8%), and gait disturbance occurred in those receiving 5 or 15 mg/d (19.6% and 17.0%, respectively). No significant cognitive impairment, increase in extrapyramidal symptoms, or central anticholinergic effects were found at any olanzapine dose relative to placebo. CONCLUSION: Low-dose olanzapine (5 and 10 mg/d) was significantly superior to placebo and well tolerated in treating agitation/aggression and psychosis in this population of patients with AD.