Re: Second-generation antipsychotics

Issue: BCMJ, vol. 54, No. 6, July August 2012, Pages 276-277 Letters

Regarding the commentary by Drs Fok and Dian on second-generation antipsychotic (SGA) use in patients with dementia [BCMJ 2012;54:169], I would like to offer a broadened perspective in light of these complex issues. Dementia is usually irreversi­ble and fatal. Therefore it makes sense to prioritize comfort, safety, and dignity as the illness progresses. 

Behavioral problems arise in up to 80% of patients with dementia and exert an enormous toll on function, quality of life, and caregiver health.[1] As emphasized by Drs Fok and Dian, the treatment of underlying factors such as pain can alleviate behavioral disturbances.[2

While worthy of consideration, nonmedication management strategies are often not applicable when acute behavioral problems pose risks to the comfort and safety of patients and others. Medications approved for use in dementia (cholinesterase inhi­bitors and memantine) do not convinc­ingly reduce acute or dangerous be­havioral disturbances[3,4] Clinicians are thus often left with basically no sanctioned op­tions for treatment of these problems.

In their commentary, Drs Fok and Dian claim that SGA trials showed only “modest” benefits. Interestingly, a recent UK government–sponsored review found that the number needed to treat (NNT) for SGAs to achieve clinically significant improvement in one additional behaviorally disturbed dementia patient was actually quite favorable, ranging from 5 to 11.[5

A re­cent evidence-based risk-benefit utility analysis concluded that there is a utility advantage to treating distressing dementia-related behavioral problems with an SGA after less risky treatment options have been exhausted.[6] SGA use has been shown to have a small but significant positive effect on caregiver burden.[7] The side-effect risks and the harm evidence for SGA exposure in patients with dementia[8] need to be considered when informed consent is discussed and documented. 

While reassessment of the need for ongoing SGA use is important since behavioral syndromes often expire as dementia progresses, it is also important to weigh the risk of re-emergent distress when previously helpful medication is re­duc­ed or withdrawn.[9] My experience has been that the benefits of judicious SGA use to reduce patient or caregiver distress almost always outweigh the side effects and longer-term morbidity/mortality risks. 

Furthermore, appropriately informed patients or substitute decision-makers almost always consent to SGA use when necessary because they consider comfort and dignity to be of utmost importance while they battle these devastating illnesses. 
—Michael J. Passmore, MD


1.    Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: Results from the cardiovascular health study. JAMA 2002;288:1475-1483.
2.    Husebo BS, Ballard C, Sandvik R, et al. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: Cluster randomised clinical trial. BMJ:15;343:d4065.
3.    Fox C, Crugel M, Maidment I, et al. Efficacy of memantine for agitation in Alzheimer’s dementia: A randomised double-blind placebo controlled trial. PLoS One 2012;7(5),e35185.
4.    Rodda J, Morgan S, Walker Z. Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer’s disease? A systematic re­view of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int Psychogeriatr 2009;21:813-824. 
5.    Banerjee S. The use of antipsychotic medication for people with dementia: Time for action. UK Department of Health. October 2009. Accessed 4 June 2012.
6.    Naarding P, van Grevenstein M, Beekman AT. Benefit-risk analysis for the clinician: “Primum non nocere” revisited—the case for antipsychotics in the treatment of behavioral disturbances in dementia. Int J Geriatr Psychiatry 2010;25:437-440.
7.    Mohamed S, Rosenheck R, Lyketsos CG, et al. Effect of second-generation antipsychotics on caregiver burden in Alzheimer’s disease. J Clin Psychiatry 2012;73:121-128.
8.    Ballard C, Hanney ML, Theodoulou M, et al., DART-AD investigators. The dementia antipsychotic withdrawal trial (DART-AD): Long-term follow-up of a random­ised placebo-controlled trial. Lancet Neurol 2009;8:151-157.
9.    Devanand DP, Pelton GH, Cunqueiro K, et al. A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer’s disease. Int J Geriatr Psychiatry 2011;26:937-943.

Michael J. Passmore, MD,. Re: Second-generation antipsychotics. BCMJ, Vol. 54, No. 6, July, August, 2012, Page(s) 276-277 - Letters.

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