Risperidone in the treatment of psychosis of Alzheimer disease: results from a prospective clinical trial.
ABSTRACT The objective of this study was to evaluate efficacy and safety of low-dose risperidone for treating psychosis of Alzheimer disease (AD).
The authors conducted a randomized, eight-week, double-blind, placebo-controlled, multicenter trial involving nursing home residents diagnosed with AD and psychosis. Four hundred seventy-three patients were randomly assigned to placebo (N = 238) or 1.0 to 1.5 mg risperidone per day (N = 235). Coprimary efficacy end points were: changes in scores on the Behavioral pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression of Change (CGI-C). Protocol-specified subgroup analyses were performed by demographics and dementia severity.
Efficacy analysis included 416 patients. Both groups improved significantly on the BEHAVE-AD Psychosis subscale and CGI-C with no significant difference between groups. In the subgroups analyses, a statistically significant treatment by Mini-Mental Status Examination (MMSE) interaction on the CGI-C (F([2,381]) = 3.90, p = 0.021) was observed with patients with more severe dementia (MMSE <10) showing significant differences at end point favoring risperidone treatment (chi(2) () = 5.11, p = 0.024). Mean risperidone dose was 1.03 +/- 0.24 mg per day. All-cause discontinuation rates were 25% for both risperidone and placebo. Treatment-emergent adverse events occurred in 74% risperidone versus 64% placebo patients, with somnolence occurring significantly more frequently with risperidone (16.2% versus 4.6%). Nine (3.8%) risperidone- and six (2.5%) placebo patients died during or within 30 days after treatment.
This trial did not confirm earlier findings in this population.
- [Show abstract] [Hide abstract]
ABSTRACT: ABSTRACT Background: In clinical practice, Second Generation Antipsychotics (SGAs) are often used as first-line treatment for the Behavioral and Psychological Symptoms of Dementia (BPSD) in older adults due to their fewer neurological adverse events and similar effectiveness compared with First Generation Antipsychotics (FGAs). SGAs, however, are associated with more severe metabolic side effects (weight gain, hyperglycemia, diabetes risk, and hyperlipidemia) than FGAs are. In general, older patients, especially those affected by dementia, are at increased risk for malnutrition, and tend to have lower basal metabolism and reduced liver and kidney function. However, little is known about the metabolic side effects of antipsychotic drugs in this population. Methods: A comprehensive review of the literature published between January 1996 and December 2012 investigating the metabolic side effects related to FGAs and SGAs use in old patients affected by dementia. Results: Antipsychotic drugs currently used to treat BPSD in subjects with mild to moderate dementia are associated with weight gain. Currently, there are insufficient data to support a causal relationship between the use of FGAs and SGAs and changes in glucose homeostasis or lipid metabolism in older persons affected by severe dementia (MMSE <14). Conclusion: A possible association between antipsychotic drugs use and weight gain might exist, in particular in subjects with mild to moderate dementia whereas no significant effects are demonstrated regarding glucose homeostasis and lipid metabolism. The antipsychotic drugs potential for causing metabolic abnormalities in older patients requires further specifically designed studies. Clinicians must be aware of this possibility even if the shorter periods of treatment administered in late-life might not be as harmful as it is in younger individuals.International Psychogeriatrics 10/2013; · 1.89 Impact Factor
- International Psychogeriatrics 04/2014; · 1.89 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Psychotic symptoms emerging in the context of neurodegeneration as a consequence of Alzheimer's disease was recognized and documented by Alois Alzheimer himself in his description of the first reported case of the disease. Over a quarter of a century ago, in the context of attempting to develop prognostic markers of disease progression, psychosis was identified as an independent predictor of a more-rapid cognitive decline. This finding has been subsequently well replicated, rendering psychotic symptoms an important area of exploration in clinical history taking - above and beyond treatment necessity - as their presence has prognostic significance. Further, there is now a rapidly accreting body of research that suggests that psychosis in Alzheimer's disease (AD+P) is a heritable disease subtype that enjoys neuropathological specificity and localization. There is now hope that the elucidation of the neurobiology of the syndrome will pave the way to translational research eventuating in new treatments. To date, however, the primary treatments employed in alleviating the suffering caused by AD+P are the atypical antipsychotics. These agents are approved by the US Food and Drug Administration for the treatment of schizophrenia, but they have only marginal efficacy in treating AD+P and are associated with troubling levels of morbidity and mortality. For clinical approaches to AD+P to be optimized, this syndrome must be disentangled from other primary psychotic disorders, and recent scientific advances must be translated into disease-specific therapeutic interventions. Here we provide a review of atypical antipsychotic efficacy in AD+P, followed by an overview of critical neurobiological observations that point towards a frontal, tau-mediated model of disease, and we suggest a new preclinical animal model for future translational research.Neuropsychiatric Disease and Treatment 01/2014; 10:2253-2262. · 2.15 Impact Factor