Evidence-Based Practice Interventions for Managing Behavioral and Psychological Symptoms of Dementia in Nursing Home Residents: Page 2 of 2

December 14, 2012


Despite safety concerns, antipsychotics are still prescribed for the treatment of behavioral problems in patients with dementia. A recent initiative by the Centers for Medicare & Medicaid Services has called for a reduction of anti-psychotic prescribing in nursing homes by 15% by the end of 2012 given that as many as 40% of residents are prescribed these drugs without a diagnosis of psychosis.10  

Conventional (first-generation) antipsychotics were the mainstay of BPSD treatment before the introduction of atypical (second-generation) antipsychotics.2 According to Madhusoodanan,3 a meta-analysis of controlled trials of conventional antipsychotics in patients with dementia showed an 18% to 26% efficacy rate over placebo. The problem with using conventional antipsychotics in elderly patients with dementia is the high incidence of adverse cardiovascular effects and high risk of death.3 Other side effects include sedation, orthostatic hypotension, and anticholinergic symptoms, such as urinary retention, dry mouth, constipation, visual difficulties, confusion, and further decline in cognitive impairment.11 Extrapyramidal symptoms, such as Parkinson-like symptoms, akathisia, dystonia, and tardive dyskinesia, are also severe side effects of conventional antipsychotics.11 The efficacy and safety profile of atypical antipsychotics is better than conventional antipsychotics in the psychopharmacological management of BPSD; however, none of the atypical antipsychotics are approved by the US Food and Drug Administration (FDA) for the treatment of BPSD.3 Atypical antipsychotics have been the most studied and used class of drugs in the management of BPSD. They have a modest efficacy rate and result in fewer extrapyramidal symptoms, including tardive dyskinesia, compared with conventional antipsychotics.3 

Risperidone is one of the most studied atypical agents in BPSD. It is associated with a higher level of somnolence when compared with a placebo, but has fewer adverse effects when it comes to extrapyramidal symptoms and falls.11 As with initiating any drug, the risks versus benefits must be discussed with the patient and his or her family.

A post-hoc exploratory analysis of data on 479 nursing home patients with psychosis associated with dementia was performed by Rabinowitz and associates.12 The study was a 12-week, double-blind, placebo-controlled clinical trial. Inclusion criteria for the trial included a diagnosis of Alzheimer’s disease or mixed dementia with a rating of more than 2 on any delusions or hallucination item of the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) upon entering the trial. Mean changes from baseline to the end of the trial were examined on the CMAI and BEHAVE-AD. The CMAI assessment showed that risperidone, compared with placebo, significantly reduced cursing or verbal aggression, hitting, repetitious mannerisms, pacing, aimless wandering, hoarding, hiding of things, and repetitive questions or sentences. On the BEHAVE-AD, risperidone showed significant efficacy in reducing physical threats and/or violence, agitation, and verbal outbursts compared with placebo. These findings led the author to conclude that risperidone is effective in treating BPSD.12 

In 2005, De Deyn and colleagues13 conducted an analysis of pooled data from three randomized, placebo-controlled trials that examined the efficacy and safety of risperidone use in treating agitation, aggression, and psychosis associated with dementia in nursing home patients. The authors’ objective was to assess the risk versus benefit of using risperidone in this population, and they found that the observed mean change at end point on the CMAI total score, total aggression score, BEHAVE-AD total score, and psychotic symptoms score was significantly higher for the risperidone group than for the placebo group. In addition, the incidence of adverse events was comparable between the risperidone and placebo groups, at 84.3% and 83.9%, respectively. Risperidone induced no orthostatic or anticholinergic adverse effects, nor did it increase falls or cognitive decline. At the recommended doses, risperidone displayed a favorable risk-benefit profile, and it was well tolerated with respect to extrapyramidal symptoms, somnolence, and anticholinergic side effects.13

However, a systematic review performed by Lee and associates14 only a year earlier concluded that although atypical anti-psychotic use has increased in the treatment of BPSD, there are few randomized trials to evaluate their use for this purpose. The authors reviewed 77 abstracts and found only five randomized trials evaluating risperidone and olanzapine. In these trials, treatment with an atypical antipsychotic showed improvement from beginning to end point compared with a placebo. There were also two trials comparing risperidone to haloperidol, but these did not find any difference in efficacy between these agents.14

According to an observational analysis that involved five consulting pharmacist sites,15 risperidone was preferred over olanzapine because of the decreased need for laxative use and fewer falls. The analysis compared side effects among nursing home residents (47% had a primary diagnosis of Alzheimer’s disease) receiving low-dose risperidone with those receiving low-dose olanzapine. In both groups, there was minimal need for lubricating eye drops and anxiolytic use decreased, but in the olanzapine group, more patients needed laxatives more often and there were more reported falls.15

Cholinesterase Inhibitors 

Cholinesterase inhibitors are medications used to help delay or prevent the symptoms of dementia from becoming worse. Well-known side effects of these medications include nausea, vomiting, diarrhea, and anorexia. Other lesser known side effects include rhinitis, fatigue, leg cramps, insomnia, abnormal dreams, myasthenia, asthenia, tremor, dizziness, headaches, bradycardia, orthostatic hypotension, syncope, urinary incontinence, seizures, gastrointestinal hemorrhage, extrapyraidal symptoms, and, very rarely, liver dysfunction.16

Donepezil, rivastigmine, and galantamine have been shown to produce some behavioral benefits over placebos in clinical trials.3 A study by Holmes and associates17 that evaluated the efficacy of donepezil in patients with mild to moderate Alzheimer’s disease and a score of more than 11 points on the Neuropsychiatric Inventory (NPI) at baseline found that patients treated with donepezil 10 mg daily had marked improvement in their NPI score compared with their placebo-treated counterparts.

Feldman and colleagues18 conducted a 24-week double-blind trial of patients with moderate to severe Alzheimer’s disease treated with donepezil 10 mg daily. This study also showed a greater reduction in NPI scores in the treatment group than in the placebo group.

In a 26-week, open-label study of rivastigmine by Cummings and colleagues,19 there was a decrease in the NPI-Nursing Homes scores for a wide range of behavioral disturbances in the subgroup of patients with behavioral symptoms at baseline. The study involved a total of 29 nursing homes, and the effects of rivastigmine 3 mg daily to 12 mg daily were assessed in residents with moderate to severe dementia.


An article by Porsteinsson20 outlined the results of four placebo-controlled clinical trials that examined the use of divalproex sodium for BPSD. The author found that the outcomes in none of the studies were sufficient to define clinical practice and the results were conflicting and inconclusive. In a review article by Kim and colleagues,21 research assessing the use of gabapentin for BPSD was evaluated. In most of the reviewed cases, gabapentin was reported to be well tolerated and an effective treatment for BPSD, but the authors concluded that lack of available data limit the support of its use in the treatment of BPSD. 


This review identified that there are many different nonpharmacological interventions that have been investigated for the treatment of BPSD in nursing homes, but the studies did not show enough clinical significance to merit changes in practice. Much larger and higher quality studies need to be performed in this area. The studies need to be conducted using nursing home staff and resources that are readily available in nursing homes. Because most nursing homes are for-profit, it would be easy to assume that not a large amount of money will be spent on outside consults or improvements in the environment. 

As for pharmacological treatments for BPSD, there have been many studies done, but no drug is free of side effects. Because most patients with dementia are elderly and take multiple medications, the addition of another agent to treat BPSD can be detrimental to their health. Also, thus far, no pharmacological treatment for BPSD has been FDA-approved. Drugs being used in the treatment of BPSD have been prescribed off-label.


  1. International Psychogeriatric Association. Behavior and psychological symptoms of dementia (BPSD) educational pack. Published 2002. Accessed November 19, 2012.
  2. Buhr GT, White HK. Difficult behaviors in long-term care patients with dementia. J Am Med Dir Assoc. 2007;8(3 suppl 2):e101-e113.
  3. Madhusoodanan S, Shah P, Brenner R, Gupta S. Pharmacological treatment of the psychosis of Alzheimer’s disease: what it the best approach? CNS Drugs. 2007;21(2):101-115.
  4. Sutor B, Rummans TA, Smith GE. Assessment and management of behavioral disturbances in nursing home patients with dementia. Mayo Clin Proc. 2001;76(5):540-550.
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  9. Bharani N, Snowden M. Evidence-based interventions for nursing home residents with dementia-related behavioral symptoms. Psychiatr Clin North Am. 2005;28(4):985-1005.
  10. US Centers for Medicare & Medicaid Services. CMS announces partnership to improve dementia care in nursing homes [news release]. May 30, 2011. Accessed November 19, 2012.
  11. Burns A, De Deyn PP. Risperidone for the treatment of neuropsychiatric features in dementia. Drugs Aging. 2006;23(11):887-896.
  12. Rabinowitz J, Katz I, De Deyn PP, Greenspan A, Brodaty H. Treating behavioral and psychological symptoms in patients with psychosis of Alzheimer’s disease using risperidone. Int Psychogeriatr. 2007;19(2):227-240.
  13. De Deyn PP, Katz IR, Brodaty H, Lyons B, Greenspan A, Burns A. Management of agitation, aggression, and psychosis associated with dementia: a pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone. Clin Neurol Neurosurg. 2005;107(6):497-508.
  14. Lee P, Gill SS, Freedman M, Bronskill SE, Hillmer MP, Rochon PA. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ. 2004;329(7457):75.
  15. Martin H, Slyk MP, Deymann S, Cornacchione MJ. Safety profile assessment of risperidone and olanzapine in long-term care patients with dementia [published correction appears in J Am Med Dir Assoc. 2003;4(5):290]. J Am Med Dir Assoc. 2003;4(4):183-188.
  16. Patel B, Holland NW. Adverse effects of acetylcholinesterase inhibitors. Clinical Geriatrics. 2011;19(1):27-30.
  17. Holmes C, Wilkinson D, Dean C, et al. The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer’s disease. Neurology. 2004;63(2):214-219.
  18. Feldman H, Gathier S, Hecker J, Vellas B, Subbiah P, Whalen E; Donepezil MSAD Study Investigators Group. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease [published correction appears in Neurology. 2001;57(11):2153]. Neurology. 2001;57(4):613-620.
  19. Cummings JL, Koumaras B, Chen M, Mirski D; Rivastigmine Nursing Home Study Team. Effects of rivastigmine treatment on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable Alzheimer’s disease: a 26-week, multicenter, open-label study. Am J Geriatr Pharmacother. 2005;3(3):137-148.
  20. Porsteinsson AP. Divalproex sodium for the treatment of behavioural problems associated with dementia in the elderly. Drugs Aging. 2006;23(11):877-886.
  21. Kim Y, Wilkins KM, Tampi RR. Use of gabapentin in the treatment of behavioural and psychological symptoms of dementia: a review of the evidence. Drugs Aging. 2008;25(3):187-196. 


    The author reports no relevant financial relationships.


    Address correspondence to:

    Rebecca Perkins, RN, BSN, BS

    111 Clinton St.

    Maumee, OH 43537