Pharmacological treatment of neuropsychiatric symptoms of dementia - A review of the evidence
ABSTRACT Neuropsychiatric symptoms of dementia are common and associated with poor outcomes for patients and caregivers. Although nonpharmacological interventions should be the first line of treatment, a wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms; therefore, concise, current, evidence-based recommendations are needed.
To evaluate the efficacy of pharmacological agents used in the treatment of neuropsychiatric symptoms of dementia.
A systematic review of English-language articles published from 1966 to July 2004 using MEDLINE, the Cochrane Database of Systematic Reviews, and a manual search of bibliographies was conducted. Inclusion criteria were double-blind, placebo-controlled, randomized controlled trials (RCTs) or meta-analyses of any drug therapy for patients with dementia that included neuropsychiatric outcomes. Trials reporting only depression outcomes were excluded. Data on the inclusion criteria, patients, methods, results, and quality of each study were independently abstracted. Twenty-nine articles met inclusion criteria.
For typical antipsychotics, 2 meta-analyses and 2 RCTs were included. Generally, no difference among specific agents was found, efficacy was small at best, and adverse effects were common. Six RCTs with atypical antipsychotics were included; results showed modest, statistically significant efficacy of olanzapine and risperidone, with minimal adverse effects at lower doses. Atypical antipsychotics are associated with an increased risk of stroke. There have been no RCTs designed to directly compare the efficacy of typical and atypical antipsychotics. Five trials of antidepressants were included; results showed no efficacy for treating neuropsychiatric symptoms other than depression, with the exception of 1 study of citalopram. For mood stabilizers, 3 RCTs investigating valproate showed no efficacy. Two small RCTs of carbamazepine had conflicting results. Two meta-analyses and 6 RCTs of cholinesterase inhibitors generally showed small, although statistically significant, efficacy. Two RCTs of memantine also had conflicting results for treatment of neuropsychiatric symptoms.
Pharmacological therapies are not particularly effective for management of neuropsychiatric symptoms of dementia. Of the agents reviewed, the atypical antipsychotics risperidone and olanzapine currently have the best evidence for efficacy. However, the effects are modest and further complicated by an increased risk of stroke. Additional trials of cholinesterase inhibitors enrolling patients with high levels of neuropsychiatric symptoms may be warranted.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: A wide variety of atypical antipsychotic drugs (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone and clozapine) are widely used in the management of neuropsychiatric symptoms, which are commonly seen in dementia, but results from randomised controlled trials (RCTs) on the efficacy and safety of these agents are conflicting. We aimed to quantify the efficacy and safety of atypical antipsychotic drugs on neuropsychiatric symptoms in dementia patients. PubMed, EMBASE, the Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews for reports published before August 2014 were searched for eligible randomized controlled trials of atypical antipsychotic drugs therapy in patients with psychotic symptoms of dementia. Two reviewers independently assessed the quality of the trials and extracted information. Overall, 23 relevant RCTs with 5,819 participants were identified. This meta-analysis demonstrated a significant efficacy of atypical antipsychotics on psychiatric symptoms and cognitive functions compared to placebo. In the meta-analysis, the weighted mean differences (WMDs) in change scores for psychiatric symptoms were in favor of aripiprazole (-4.4, 95% confidence interval (CI) - 7.04 to -1.77) and risperidone (-1.48, 95% CI -2.35 to -0.61) compared to placebo. In cognitive effects, WMDs in change scores for the Clinical Global Impression-Change (CGI-C) were in favor of aripiprazole, risperidone, olanzapine and quetiapine which ranged from a -0.30 points mean difference (95% CI:-0.59 to -0.01) in the aripiprazole trials to -0.43 (95% CI:-0.62 to -0.25) in the risperidone group. Patients receiving atypical antipsychotics showed no difference in risk for injuries or falls (P > 0.05), significantly higher risks (P < 0.05) for somnolence, urinary tract infection, edema and abnormal gait. However, there was no significant evidence for death reported. Aripiprazole and risperidone are able to improve psychiatric symptoms and slow decline in cognition function at average 12 weeks in patients with neuropsychiatric symptoms of dementia. However, high adverse events may offset the efficacy of atypical antipsychotics in dementia.Alzheimer's Research and Therapy 12/2015; 7(1). DOI:10.1186/s13195-015-0102-9 · 3.50 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The objective of our study was to demonstrate that living with a person affected by mild to moderate Alzheimer's disease can lead to an increased perception of the caregiver's burden using the Caregiver Burden Inventory (CBI). The sample consisted of 153 dyads, caregiver-patient. At baseline, a greater perception of the caregiver's burden was observed in the live-in caregivers. A further increase in the total burden of the live-in caregivers was noticed at the 6-month follow-up. More specifically, with the inclusion of correction factors such as the caregiver's age and the CBI subscales at baseline, the social and emotional burden becomes statistically significant (P < .001). The present paper confirms our hypothesis that live-in caregivers perceive a greater burden than nonlive-in, and this difference increases further after 6 months. The difference in involvement between live-in and nonlive-in caregivers could be the foundation to tailor more specific interventions. © The Author(s) 2015.
[Show abstract] [Hide abstract]
ABSTRACT: Apathy is a common feature of neurodegenerative disorders but is difficult to study in a clinical trial setting due to practical and conceptual barriers. Principal challenges include a paucity of data regarding apathy in these disorders, an absence of established diagnostic criteria, the presence of confounding factors (eg, coexisting depression), use of concomitant medications, and an absence of a gold-standard apathy assessment scale. Based on a literature search and ongoing collaboration among the authors, we present recommendations for the design of future clinical trials of apathy, suggesting Alzheimer disease and Parkinson disease as models with relevance across a wider array of neuropsychiatric disorders. Recommendations address clarification of the targeted study population (apathy diagnosis and severity at baseline), confounding factors (mood/cognition, behavior, and treatment), outcome measures, study duration, use of comparators and considerations around environment, and the role of the caregiver and patient assent. This review contributes to the search for an optimal approach to study treatment of apathy in neuropsychiatric disorders. © The Author(s) 2015.Journal of Geriatric Psychiatry and Neurology 03/2015; DOI:10.1177/0891988715573534 · 1.63 Impact Factor