The Efficacy and Safety of Atypical Antipsychotics for the Treatment of Dementia: A Meta-Analysis of Randomized Placebo-Controlled Trials

Abstract

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.

An overview of systematic reviews of pharmacological and non-pharmacological interventions for the treatment of behavioral and psychological symptoms of dementia

“…Atypical antipsychotics (Ma, 2014) Significantly higher risk for somnolence, extrapyramidal symptoms, cerebrovascular adverse events, urinary tract infections, edema, gait abnormality, and death compared to placebo. Some adverse effects had incidence rates of >5% and were observed in most trials.…”

A preclinical screen to evaluate pharmacotherapies for the treatment of agitation in dementia

“…The most contentious approach relates to the use of antipsychotic drugs , which have been reported to be of only modest value (Ballard et al, 2009;, and to produce adverse effects (Gitlin et al, 2012). Overall, the currently available pharmacological treatments for agitation in dementia are of little value, and the adverse effects of antipsychotic drugs are of considerable concern (Sacchetti et al, 2012;Ma et al, 2014;Ballard, 2006;. Basically, there are no officially approved pharmacotherapies for agitation in dementia, and few if any safe and effective pharmacotherapies (Antonsdottir et al, 2015;Cummings et al, 2015;Panza et al, 2015;Soto et al, 2015;Kales et al, 2014;.…”

“…Of the pharmacological treatments used for the management of agitation in dementia, benzodiazepines (anxiolytics) have weak effects (Defrancesco et al, 2015;Ngo and Holroyd-Leduc, 2015;Kales et al, 2014;Wilson et al, 2012;Salzman et al, 2008) and have been found to accelerate cognitive deterioration (Defrancesco et al, 2015), the antidepressants citalopram (Pollock et al, 2002) and sertraline (Lyketsos et al, 2003) have been suggested to have some effects (Sink et al, 2005), however the trial using citalopram had a high dropout rate due to lack of efficacy and sertraline had no benefit with respect to neuropsychiatric symptoms. Antipsychotics are of modest value (Gitlin et al, 2012;Ballard et al, 2009) but induce adverse cerebrovascular events, especially during the first weeks of treatment (Wu et al, 2013;Sacchetti et al, 2012) and increase mortality (Ma et al, 2014;Sacchetti et al, 2012;Ballard, 2006;, and anticonvulsants raise concerns with respect to tolerability (Gallagher and Herrmann, 2014).…”

Association between antipsychotics and adverse outcomes in dementia

“…Research into other adverse outcomes is limited. Such studies include three literature reviews [6][7][8] , a meta-analysis 9 , two systematic reviews 10,11 . This study was undertaken to investigate the rate of use of antipsychotics in patients with dementia and the rate of any adverse outcome known to be associated with their use.…”