Re: Second-generation antipsychotic medications

We read the article “Prescribing second-generation antipsychotic medications: Practice guidelines for general prac­titioners” [BCMJ 2012;54:75-82] with great interest and applaud the efforts of Ms Horn and colleagues on their practical and useful guide for prac­titioners concerning a class of medications that are increasingly being prescribed for a wide variety of psych­iatric and behavioral conditions.[1

We feel, however, that older adults with dementia deserve particular em­phasis. Second-generation antipsycho­tics are widely used in this group, but the evidence supporting their use remains limited. The two second-generation antipsychotics that have been studied in randomized controlled trials (risperidone and olanzapine) demonstrate only modest benefits in the context of a short duration ranging from 24 hours to 12 weeks.[2

This comes at the cost of an increased risk of mortality from meta-analyses (odds ratio of 1.54 to 1.7), and possibly an increased risk of stroke.[3,4] For these reasons, second-generation antipsychotics have black box warnings cautioning their use in older adults and do not have formal approval by the US Food and Drug Administration for treatment of behavioral and psychotic symptoms in patients with dementia. 

Clinicians need to be aware of these risks and discuss them with patients and families before initiating therapy. Before ascribing the behavior to the behavioral and psychotic symptoms in patients with depression it is essential to screen for and treat other conditions such as delirium, agitated depression, pain and infections. Nonpharmacological interventions such as anticipating unmet needs, avoiding triggers, and use of music therapy may be helpful.[5

We recognize that managing be­havioral symptoms related to dementia is often challenging. When second-generation antipsychotics are used they should be reserved for severe symptoms when the benefits are felt to outweigh the risks and for a defined period of time with frequent reassessment.
—Mark Fok, MD
—Larry Dian, MD


1.    Horn M, Procyshyn RM, Warburton WP, et al. Prescribing second-generation anti­psychotic medications: Practice guidelines for general practitioners. BC Med J 2012;54:75-82.
2.    Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 2005;293:596-608.
3.    Kuehn BM. FDA warns antipsychotic drugs may be risky for elderly. JAMA 2005;293:2462.
4.    Schneider LS, Dagerman KS, Insel PS. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analy­sis of randomized placebo-controlled trials. JAMA 2005;294:1934-1943.
5.    Ayalon L, Gum AM, Feliciano L, et al. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med 2006;166:2182-2188.

Mark Fok, MD, FRCPC, Larry Dian, MB, BCH, FRCPC. Re: Second-generation antipsychotic medications . BCMJ, Vol. 54, No. 4, May, 2012, Page(s) 169 - Letters.

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