Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review

Abstract

Objective To review the role of oral atypical antipsychotic drugs in the management of the behavioural and psychological symptoms of dementia (BPSD). Data sources Medline, Embase, and the Cochrane Library. Reference lists were reviewed and experts were contacted to identify additional trials. Study selection Double blind randomised controlled trials that evaluated the four oral atypical antipsychotic therapies for BPSD. Review methods Two reviewers assessed trial validity independently. Data extraction Demographics of patients, study duration, dose of antipsychotic, primary end points, adverse events. Results 77 abstracts were reviewed. Five randomised trials (1570 patients) evaluating risperidone and olanzapine were identified. The quality of trials was generally good. Most participants were in an institution ( > 96%), elderly (weighted mean 82.3 years), and had Alzheimer's disease (76.3%). Trials lasted 6-12 weeks. Treatment with atypical antipsychotic drugs was superior to placebo for the primary end point in three of the five trials. Two trials comparing risperidone with haloperidol did not find any differences in the primary measures of efficacy. Adverse events were common and included extrapyramidal symptoms, somnolence, and abnormal gait. Conclusions Although atypical antipsychotic drugs are being used with increasing frequency, few randomised trials have evaluated their use for BPSD. Limited evidence supports the perception of improved efficacy and adverse event profiles compared with typical antipsychotic drugs.

Profile of atypical-antipsychotics use in patients affected by dementia in the University Hospital of Ferrara

“…The daily doses used to control behavior disturbances during dementia were in agreement with the dosages reported in main published research [14,25] and were very much lower than those used for the treatment of more serious psychoses.…”

“…Their use is rarely associated with extrapyramidal symptoms, at least in therapeutic doses, and they seem to control negative symptoms of schizophrenia (apathy, catatony, lack of thoughts). Therefore, atypical antipsychotic drugs have replaced the traditional drugs [15] though their use for treating BPSD still remains off-label [14]. Moreover, after some reports of cardiovascular events [16][17][18][19] in 2004, many national regulatory agencies published official warnings recommending adherence to label indications [20][21][22].…”

A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors

“…Benzodiazepines, b-blockers and antidepressants may cause sedation and a worsening of cognitive function. Haloperidol may alleviate delusional behaviour but may cause motor-related AEs, while concerns have been raised about atypical antipsychotics such as risperidone, quetiapine and olanzapine in elderly patients with dementia due to an increased risk of stroke and increased mortality rates (Lawlor, 2004;Lee et al, 2004;Tariot et al, 2004;Schneider et al, 2005). Among elderly patients, the mortality risk associated with conventional antipsychotics has also been reported as comparable to and possibly greater than the risk of death associated with atypical antipsychotics (Schneeweiss et al, 2007).…”

Antipsychotics and cognitive decline in Alzheimer's disease: the LASER-Alzheimer's disease longitudinal study

“…[14][15][16] Two recent systematic reviews report only a modest improvement in neuropsychiatric symptoms from atypicals 17 and none from typical antipsychotics. 18 Typical antipsychotics have been associated with higher mortality than atypicals in older people with and without dementia. 19 However, a recent meta-analysis of RCTs showing that in dementia, atypical antipsychotics are associated with a small increase in death rate has increased treatment concerns.…”