The purpose of this review is to evaluate the data on the use of antipsychotics in individuals with dementia from meta-analyses. The search was not restricted by the age of the patients or the language of the study. However, in the final analysis we only included studies involving patients that were published in English language journals or had official English translations. In addition, we reviewed the bibliographic databases of published articles for additional studies.
This systematic review of the literature identified a total of 16 meta-analyses that evaluated the use of antipsychotics in individuals with dementia. Overall, 12 meta-analyses evaluated the efficacy of antipsychotics among individuals with dementia. Of these, eight also assessed adverse effects. A further two studies evaluated the adverse effects of antipsychotics i. A total of two meta-analyses evaluated the discontinuation of antipsychotics in individuals with dementia.
The rest of the 12 meta-analyses included individuals with dementia. Antipsychotics have demonstrated modest efficacy in treating psychosis, aggression and agitation in individuals with dementia.
Their use in individuals with dementia is often limited by their adverse effect profile. The use of antipsychotics should be reserved for severe symptoms that have failed to respond adequately to nonpharmacological management strategies. Antipsychotic medications are often used to treat behavioral and psychological symptoms of dementia BPSD [ Zuidema et al. In addition, individuals "Most sedating anti psychotics and dementia" dementia who live in skilled nursing facilities have significantly greater rates of prescription of antipsychotic medications when compared with those individuals living in the community [ Maguire, ].
However, similar benefits have not been observed for quetiapine. In addition, there is limited evidence for the use of these medications in individuals with non-AD type dementia [ Ballard et al.
Furthermore, the benefit of using antipsychotics as a "Most sedating anti psychotics and dementia" treatment in individuals with dementia is unclear. The use of antipsychotics in the management of psychotic symptoms and aggression in individuals with dementia must be balanced against their serious adverse effects profile [ Ballard et al. Antipsychotic use increases the risk for death, cerebrovascular adverse events CVAEsParkinsonism, sedation, gait disturbance, cognitive decline and pneumonia [ Ballard et al.
Data also indicate that the risk for mortality remains elevated for at least 2
Most sedating anti psychotics and dementia, and the actual number of deaths due to antipsychotics increases with their longer duration of use. The US FDA has not yet approved any medication for treating agitation associated with dementia and AD and in the European Union and Australia only risperidone is indicated for the short-term management of persisting and severe aggression in individuals with AD who have failed nonpharmacological trials [ Maher et al.
Despite these warnings, the off-label use of antipsychotics for treating individuals with dementia appears to have grown over the past two decades. Numerous reviews have evaluated the use of antipsychotics in individuals with dementia [ Gallagher and Herrmann, ; Madhusoodanan and Ting, ; Gareri et al.
However, none of these reviews have systematically studied the data on the use of antipsychotics in individuals with dementia exclusively from meta-analyses. Systematic reviews and meta-analyses of well-designed and completed randomized controlled trials RCTs can provide the highest levels of evidence to support therapeutic interventions [ McNamara and Scales, ; Sauerland and Seiler, ].
In order to fill this void in the literature, we decided to conduct a systematic review of meta-analyses that evaluated the use of antipsychotics in individuals with dementia. Our goal was to assess the highest level of evidence on the use of antipsychotics in individuals with dementia so that these data can be used to improve the care of these vulnerable individuals. The review of all the abstracts and full-text articles from the citations obtained via the search of the databases was carried out by three of the authors RRT, DJT and SC.
The decision on which studies to be included or excluded from the final analysis was done after a review of the full-text articles by all the authors.
Disagreements between the authors were resolved by a consensus. This systematic review of the literature identified a total of 16 meta-analyses that evaluated the use of antipsychotics in individuals with dementia [ Schneider et al. Among the 16 meta-analyses, 12 evaluated the efficacy of antipsychotics among individuals with dementia [ Schneider Most sedating anti psychotics and dementia al. There were two studies that evaluated the adverse effects of antipsychotics i.
A total of two studies focused on the discontinuation of antipsychotics among individuals with dementia [ Declercq et al. There were three meta-analyses that were conducted in individuals with AD Most sedating anti psychotics and dementia Ballard and Waite, ; Katz et al. The rest of the 12 meta-analyses included individuals with dementia [ Schneider et al. A total of seven of the meta-analyses were completed prior to [ Schneider et al.
In the next section we describe the data on efficacy, adverse effects and the evidence for discontinuation of antipsychotics in individuals with dementia. This section contains data from 12 meta-analyses that evaluated the efficacy of antipsychotics in individuals with dementia [ Schneider et al.
The meta-analyses have been arranged in a chronological order with the oldest study first and the latest study at the end. In the earliest meta-analysis that was identified in this review, Schneider and colleagues evaluated the use of typical antipsychotic medications in individuals with dementia [ Schneider et al.
The investigators found that these medications were more effective than placebo in treating agitation in dementia with a modest effect size 0. They found that when thioridazine and haloperidol were compared with the other typical antipsychotics there was no significant difference noted between these two drugs and the other medications.
In a meta-analysis that evaluated the use of thioridazine in individuals with dementia, the investigators found Most sedating anti psychotics and dementia, when compared with placebo, thioridazine reduced symptoms of anxiety in these individuals [ Kirchner et al.
However, there were no significant effects noted on clinical global change in thioridazine-treated individuals when compared with placebo. Thioridazine was found to be superior to diazepam for anxiety symptoms. Both medications did not improve global clinical evaluation scales in individuals with dementia. Thioridazine was found to be inferior to chlormethiazole in managing behavioral symptoms.
Thioridazine was no better than etoperidone, loxapine or zuclopenthixol when used in individuals with dementia. In the meta-analysis by Ballard and Waite, the investigators found that among individuals with dementia, the use of risperidone and olanzapine improved aggression when compared with placebo [ Ballard and Waite, ]. In addition, they found that the use of risperidone also improved psychotic symptoms among these individuals.
Schneider and colleagues, in their meta-analysis evaluating the use of atypical antipsychotics for dementia, found efficacy for aripiprazole and risperidone but not for olanzapine when used in these individuals [ Schneider et al.
They also noted smaller effects for less-severe dementia, outpatients and individuals with psychotic symptoms. Most sedating anti psychotics and dementia the meta-analysis by Yuri and Fisher, the investigators included data from "Most sedating anti psychotics and dementia" studies that compared risperidone, olanzapine, and quetiapine with either placebo or with each other [ Yury and Fisher, ]. The investigators found the overall mean effect size from the seven placebo-controlled studies for primary measures to be 0.
For all measures of behavioral problems, the mean effect size was 0. In a meta-analysis, Katz and colleagues compared data from four large placebo-controlled clinical trials of risperidone in individuals with psychosis of AD or dementia [ Katz et al. Secondary analyses indicated that individuals with more severe symptoms showed better response to treatment with risperidone when compared with placebo effect size 1.
Maher and colleagues in their meta-analysis used data from 18 RCTs that evaluated the use of atypical antipsychotic medications in individuals with dementia [ Maher et al. They examined three types of outcomes: The investigators found that for aripiprazole, olanzapine and risperidone, the effect size for treating these symptoms was small 0. The effect size for quetiapine was 0.
The investigators also found that aripiprazole 10 mg a day or risperidone 2 mg a day may be more effective than lower doses in treating the behavioral symptoms. For the treatment of psychosis, the effect sizes were 0.
Aripiprazole, olanzapine and risperidone were all associated with statistically significant improvements in agitation with effect sizes between 0.
The three trials that compared risperidone with olanzapine or risperidone with quetiapine did not find any significant difference between these drugs for treating behavioral symptoms. A total of five trials that Most sedating anti psychotics and dementia an atypical antipsychotic medication with haloperidol for the total global outcome also did not consistently identify any statistically significant difference between these drugs.
In a meta-analysis that evaluated all pharmacological treatment strategies for individuals with LBD the investigators could not conduct a meta-analysis of antipsychotic medications as there was an inadequate number of eligible studies [ Stinton et al.
However, the investigators found a secondary analysis of a RCT that used olanzapine in individuals with AD who were retrospectively identified as meeting the LBD criteria [ Cummings et al. The investigators did not find significant differences between the olanzapine 10 mg and the 15 mg groups and the placebo groups on psychiatric symptoms. The investigators also found a randomized placebo-controlled trial of quetiapine among individuals with LBD dementia and AD with Parkinsonian features [ Kurlan et al.
They found no difference on measures of Most sedating anti psychotics and dementia symptoms between the quetiapine and the placebo-treated groups in this study. The two meta-analyses that studied the use of typical antipsychotics found that these medications have modest efficacy when used in individuals with dementia.