Document Detail

Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence.
MedLine Citation:
PMID:  15687315     Owner:  NLM     Status:  MEDLINE    
CONTEXT: 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.
OBJECTIVE: To evaluate the efficacy of pharmacological agents used in the treatment of neuropsychiatric symptoms of dementia.
EVIDENCE ACQUISITION: 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.
EVIDENCE SYNTHESIS: 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.
CONCLUSIONS: 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.
Kaycee M Sink; Karen F Holden; Kristine Yaffe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  JAMA     Volume:  293     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-02     Completed Date:  2005-02-07     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  596-608     Citation Subset:  AIM; IM    
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MeSH Terms
Antidepressive Agents / therapeutic use
Antipsychotic Agents / therapeutic use
Central Nervous System Agents / therapeutic use*
Dementia / complications*
Mental Disorders / complications*,  drug therapy*
Neurotransmitter Agents / therapeutic use
Psychotropic Drugs / therapeutic use
Grant Support
R01 AG021918-01/AG/NIA NIH HHS
Reg. No./Substance:
0/Antidepressive Agents; 0/Antipsychotic Agents; 0/Central Nervous System Agents; 0/Neurotransmitter Agents; 0/Psychotropic Drugs
Comment In:
ACP J Club. 2005 Jul-Aug;143(1):14   [PMID:  15989302 ]
JAMA. 2005 May 11;293(18):2212; author reply 2212   [PMID:  15886375 ]
JAMA. 2005 May 11;293(18):2211-2; author reply 2212   [PMID:  15886374 ]
Evid Based Ment Health. 2005 Aug;8(3):83   [PMID:  16043625 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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