Meta-analysis of the effectiveness of atypical antipsychotics for the treatment of behavioural problems in persons with dementia
ABSTRACT To review published reports of the usage of atypical antipsychotics for behavioural problems of dementia patients.
The electronic database Medline was searched from 1999 to 2006 with a combination of search terms including 'behavioural problems' and 'atypical antipsychotics'.
Thirteen eligible studies were included in the overall analysis. The total number of participants was 1,683, of whom 1,015 received medication and 668 received placebo. Medications studied were risperidone, olanzapine, and quetiapine. Other studies examined other types of medications, such as typical versus atypical antipsychotics, but only data for atypical antipsychotics were included in the meta-analysis. The mean effect size for 7 placebo-controlled studies was 0.45 (95% CI = 0.16-0.74) for atypical antipsychotics, and 0.32 (95% CI = 0.10-0.53) for placebo. The mean effect size of all 13 studies included in the analysis was 0.31 (95% CI = 0.08-0.54).
In general, effect sizes of atypical antipsychotics for behavioural problems are medium, and there are no statistically or clinically significant differences between atypical antipsychotics and placebo.
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ABSTRACT: Behavioural and psychological symptoms of dementia are distressing for patients and are frequently treated with second-generation antipsychotics. Concerns about the drugs' safety resulted in a Medicines and Healthcare Products Regulatory Agency (MHRA) warning against their use in March 2009. Second-generation antipsychotic drug use was determined amongst patients with dementia admitted to the University Hospitals Birmingham National Health Service Foundation Trust, between July 2005 and December 2011. An interrupted time series analysis was carried out to investigate changes in rates of prescribing following the safety warning. Risperidone was analysed separately, in accordance with its limited licence for use in older adults with dementia, granted in October 2008. Before the safety warning, second-generation antipsychotic use was increasing in patients with dementia. After the MHRA warning, their use fell by 1.9% per month compared with that before. Use of risperidone continued to rise over the same period, often against the terms of its licence. Drug safety warnings may influence prescribing practice, although continued use of antipsychotics in dementia could reflect a lack of alternative treatment options.Journal of Public Health 03/2014; DOI:10.1093/pubmed/fdu023 · 2.30 Impact Factor
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ABSTRACT: With an increase in the global prevalence of dementia, there is also an increase in behavioural and psychological symptoms of dementia (BPSD) for which antipsychotic drugs are often used. Despite several safety warnings on antipsychotic use in dementia, there is little evidence to support the efficacy of antipsychotics in individual BPSD symptoms or to evaluate the drug safety profile by individual antipsychotic drug. There is emerging but scarce evidence that suggests an inter-drug variability between antipsychotic safety outcomes in BPSD. The objective of this review was to examine the existing literature on antipsychotic drug use in dementia patients; in particular to see whether inter-drug differences regarding antipsychotic safety were reported. A literature search was conducted for observational studies published in the English language from 2004 to 2014 that reported the risk of all-cause mortality, cerebrovascular events, pneumonia and other outcomes such as hip/femur fracture, deep vein thrombosis (DVT) and hyperglycaemia. Six of 16 mortality studies (38 %), 7 of 28 stroke studies (25 %), 1 of 6 pneumonia (17 %) studies and 2 of 6 fracture studies (33 %) investigated inter-drug safety outcomes in elderly patients/dementia patients, while to our knowledge, there are no studies investigating the inter-drug variation of deep-vein thrombosis and hyperglycaemia risk. The results of the observational studies provide mixed results on the safety of antipsychotics in BPSD but it is clear that there are differences between the safety profiles of antipsychotic drugs. Robust evidence of such inter-drug variability could significantly improve patient safety as antipsychotics become more targeted to clinical risk factors.Drug Safety 05/2014; 37(7). DOI:10.1007/s40264-014-0170-y · 2.62 Impact Factor
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ABSTRACT: Background: The application of atypical antipsychotics (SGAs) for treatment of psychiatric and behavioral symptoms of dementia is controversial since their efficacy might be offset by their adverse events (AEs). Objective: To assess the efficacy, safety, and tolerability of SGAs for treatment of psychological and behavioral symptoms of dementia. Methods: Two researchers searched MEDLINE, PsychINFO, and the Cochrane Central Register of Controlled Trials independently for double-blind, placebo-controlled, randomized controlled trials (DB-PC-RCTs) as of June 2013, written in English. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI), Clinical Global Impression of Change (CGI-C), and (or) Clinical Global Impression of Severity (CGI-S). Safety and tolerability were measured by frequencies of drop-outs, adverse events (AEs), and death. In total, 19 treatment comparisons drawn from 16 DB-PC-RCTs were included, and 3,343 patients randomized to the antipsychotic group and 1,707 to the placebo group were assessed. Results: This meta-analysis demonstrated a significant efficacy of atypical antipsychotics on BPRS (MD = -1.58, 95% CI = -2.52 - -0.65), CMAI (-1.84, -3.01 - -0.61), NPI (-2.81, -4.35 - -1.28), CGI-C (-0.32, -0.44 - -0.20), and CGI-S (-0.19, -0.30 - -0.09), compared to placebo (p < 0.01 for all). Patients receiving atypical antipsychotics showed no difference in risk for discontinuation (p > 0.05), significantly higher risks (p < 0.05 for all) for somnolence (OR = 2.95), extrapyramidal symptoms (1.74), cerebrovascular AEs (2.50), urinary tract infection (1.35), edema (1.80), gait abnormality (3.35), and death (1.52), and a lower risk for agitation (OR = 0.80, p = 0.03). Conclusions: The higher risks for AEs and mortality may offset the efficacy of atypical antipsychotics for treatment of dementia. Efficacy, safety, and tolerability thus should be carefully considered against clinical need.Journal of Alzheimer's disease: JAD 07/2014; 42(3). DOI:10.3233/JAD-140579 · 3.61 Impact Factor