NPS Prescribing Practice Review 43: Treating the symptoms of dementia NPS Prescribing Practice Review 43: Treating the symptoms of dementia

Identify and modify triggers of challenging behaviours

Observe the circumstances of behavioural and psychological symptoms of dementia to identify possible triggers. Such symptoms may arise from:

• visual or hearing impairment
• boredom or lack of stimulation
• use of certain medications (anticholinergics, anticonvulsants)
• loud noise or excessive, or poor, heating
• unfamiliar surroundings or routines
• carer behaviour.

Changes to these factors may help alleviate behavioural and psychological symptoms.

Refer patients and carers to information and support services

Alzheimer’s Australia (1800 100 500) offers information and support for people with Alzheimer’s disease and their carers and families. The Commonwealth’s Dementia website and its Dementia Resource Guide offers information to help people with dementia and their carers.

Benefits of cholinesterase inhibitors and memantine are small, some patients will not respond, and adverse effects are common

Drugs modify symptoms not disease progression

The cholinesterase inhibitors (donepezil [Aricept], rivastigmine [Exelon] and galantamine [Reminyl]) and memantine (Ebixa) do not alter the pathology of Alzheimer’s disease.[3] These drugs are used to improve symptoms only.

The cholinesterase inhibitors are only PBS listed for mild to moderate Alzheimer’s disease. Memantine is only PBS listed for moderately severe Alzheimer’s disease.

Expect modest improvements only

Taking a cholinesterase inhibitor for 6 months produces an average difference in cognition scores of 2 to 3 points on the 70-point ADAS-cog[A][4] compared with placebo.[5] Using memantine for 6 months produces an average difference in cognition scores of 3 points on the 100-point Severe Impairment Battery (SIB)[6] compared with placebo.[7] The clinical importance of these improvements is unclear.[8]

Not everyone responds to treatment

Not every patient with dementia benefits from drug therapy. Some patients will have clinically important improvements, but there is no way of predicting who will benefit.[1]

Adverse effects are common

In some clinical trials, half of the patients taking cholinesterase inhibitors withdrew because of adverse effects.[8] Gastrointestinal adverse effects — such as nausea, vomiting and diarrhoea — are common initially and after dose escalation. People may also experience insomnia, dizziness, cramps, vivid dreams, asthma, slow heart beat and incontinence.[3,9]

Up to 12% of patients in clinical trials stopped taking memantine because of adverse effects.[8] Common adverse effects with memantine include confusion, dizziness, drowsiness, headache, insomnia, agitation and hallucinations.[9]

[A] Alzheimer’s Disease Assessment Scale–cognitive subscale.

Monitor and objectively assess the effectiveness of cholinesterase inhibitors and memantine if they are to be used

Measure and record cognition at baseline and within 6 months of starting drug therapy

Use the MMSE (or SMMSE)[B] to measure baseline cognition and determine if the patient is eligible to try a cholinesterase inhibitor or memantine on the PBS.[10,11] If the MMSE is ≥ 25, a baseline ADAS-cog must be specified. Further information about these measures can be found in NPS News 59.

Any beneficial effect usually occurs within 3 months of starting the highest tolerated dose.[8] To continue either class of drug under the PBS, the baseline MMSE must improve by 2 points within 6 months of beginning therapy.[11]

It may be worth trying another drug if the patient does not respond to the first drug but there is no clear evidence to show that switching will produce a response.[3]

If slowing decline in cognition is no longer a goal (e.g. severe dementia), treatment with a cholinesterase inhibitor or memantine is no longer appropriate.[8]

In trials, many patients on placebo responded to treatment

Up to a third of people taking placebo in trials of the cholinesterase inhibitors showed a clinically significant improvement.[8] Up to a quarter of people taking placebo showed a clinically significant improvement in trials of memantine.[12,13]

[B] Mini-Mental State Examination or Standardised Mini-Mental State Examination.

Trial a withdrawal of antipsychotics if there are no clear beneficial effects

Reserve antipsychotics for patients who have not responded to non-drug strategies

Behavioural and psychological symptoms of dementia become more common as dementia progresses. Use antipsychotics only when non-drug strategies do not benefit patients who have distressing agitation, aggression or psychoses.

Antipsychotics increase the risk of mortality, stroke and extrapyramidal symptoms in patients with dementia.[14–16] Prescribe only after an individual assessment of the benefits and harms, and as an adjunct to non-drug strategies.

Any response will be seen in the first few weeks

Response to antipsychotics usually occurs after 1–2 weeks and clinical improvement should be expected within 12 weeks.[9,17] Discontinue if there is no improvement, and reassess the patient.

Stopping antipsychotics does not usually worsen behaviour

Many patients do not show worsening behaviour after antipsychotics are withdrawn.[14,18] Review antipsychotic use within 3 months and, if symptoms are stable, gradually withdraw as part of a trial cessation.

Avoid stopping antipsychotics abruptly when withdrawing treatment — taper the dose by 50% every 2 weeks and stop after 2 weeks on the minimum dose.[19]

Plan to review medications regularly as well as opportunistically

Before starting cholinesterase inhibitors or memantine review current medications to identify drugs (e.g. antidepressants, anticholinergics) that may exacerbate the symptoms of dementia.[1]

Review cholinesterase inhibitor or memantine use every 6 months

Review the response to the cholinesterase inhibitors or memantine by MMSE score and global, functional and behavioural assessment.[1,20] Stop treatment if there are significant side effects, poor adherence, failure to meet the chosen treatment outcomes, or a significant deterioration in the patient’s condition.[1] Ensure that the deterioration is not due to an untreated concomitant illness before discontinuing.

Review antipsychotic use every 3 months

Review the patient for their target behaviour, changes in function and treatment-related adverse effects every 3 months, or according to clinical need.[20]

Avoid anticholinergic drugs

Anticholinergic drugs impair cognition and directly oppose the action of cholinesterase inhibitors.[9,21] Commonly used anticholinergic drugs include drugs for urinary incontinence, antihistamines and some antidepressants and antipsychotics. Examples of anticholinergic drugs to avoid are provided in NPS News 59.

Counsel patients and their carers on the limited benefits of drug therapy

Regularly discuss management with patients and carers

Set aside time with the patient, their family and carers to discuss their expectations of non-drug management of dementia, medications and clinical improvement.

Reinforce the importance of non-drug strategies in promoting and maintaining independence, maintaining cognitive function and managing behavioural and psychological symptoms of dementia.

Discuss the limitations of the cholinesterase inhibitors and memantine

When initiating drug therapy discuss the following with the patient, their family and carers:

• cholinesterase inhibitors and memantine treat the symptoms of dementia and cannot cure the underlying condition
• cholinesterase inhibitors and memantine do not work for everyone and the response to the drug cannot be predicted
• drug therapy will be trialled for up to 6 months
• continuing the drug after this time requires demonstrated improvement in cognitive function
• even if the patient initially responds to the drug, it usually needs to be ceased in those with severe dementia.

Expert reviewers

A/Prof Gerard J. Byrne 
Head, Discipline of Psychiatry, School of Medicine
The University of Queensland
Brisbane, QLD

Prof Michael Woodward
Medical Director, Aged and Residential Care,
Heidelberg Repatriation Hospital,
Austin Health, Victoria

References

1. Royal Australian College of General Practitioners. Care of patients with dementia in general practice: guidelines Sydney: NSW Department of Health, 2003.
2. National Collaborating Centre for Mental Health. Dementia: a NICE–SCIE guideline on supporting people with dementia and their carers in health and social care. London: British Psychological Society, 2007.
3. Neurology Writing Group. Therapeutic Guidelines: Neurology. Version 2 ed. Melbourne: Therapeutic Guidelines Ltd, 2002.
4. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry 1984;141:1356-64.
5. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 2006:CD005593.
6. Saxton J, Swihart AA. Neuropsychological assessment of the severely impaired elderly patient. Clin Geriatr Med 1989;5:531-43.
7. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev 2006:CD003154.
   
8. Qaseem A, Snow V, Cross JT, Jr., et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2008;148:370-8.
9. Australian Medicines Handbook 2008. Adelaide: Australian Medicines Handbook Pty Ltd, 2008.
10. Pharmaceutical Benefits Advisory Committee. Positive Recommendations made by the PBAC - March 2008. Canberra: Australian Government Department of Health and Ageing, 2008. (accessed 5 May 2008).
11. Department of Health and Ageing. PBS for Health Professionals. Canberra, 2008. (accessed 1 May 2008).
12. Bakchine S, Loft H. Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. J Alzheimers Dis 2007;11:471-9.
13. Reisberg B, Doody R, Stoffler A, et al. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003;348:1333-41.
14. Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev 2006:CD003476.
15. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934-43.
16. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med 2006;355:1525-38.
17. Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006;14:191-210.
18. Ruths S, Straand J, Nygaard HA, et al. Stopping antipsychotic drug therapy in demented nursing home patients: a randomized, placebo-controlled study -The Bergen District Nursing Home Study (BEDNURS). Int J Geriatr Psychiatry 2008.
19. Department of Veteran's Affairs. Antipsychotics in dementia. Therapeutic Brief 2007. (accessed 10 May 2008).
    
20. National Institute for Health and Clinical Excellence, Social Care Institute for Excellence. Dementia: Supporting people with dementia and their carers in health and social care. NICE clinical guideline 42. London: National Institute for Health and Clinical Excellence, 2006. (accessed 27 June 2008).
21. Gill SS, Mamdani M, Naglie G, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med 2005;165:808-13.