Lewy Body Dementia: The Litmus Test for Neuroleptic Sensitivity and Extrapyramidal Symptoms
J Clin Psychiatry 2004;65(suppl 11):16-22
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a neurodegenerative
disorder now considered to be the second most common cause of dementia after Alzheimer’s
disease. Postmortem findings suggest that DLB accounts for 20% to 34% of all dementia cases and is
often underdiagnosed. Salient features of DLB include fluctuations in cognition, perceptual abnormalities
(e.g., visual hallucinations), and mild parkinsonism. Other symptoms include frequent falls,
nighttime agitation, and depression. DLB symptomatology can be partly explained by the extensive
destruction of dopaminergic and acetylcholinergic pathways caused by neurodegeneration. For this
reason, DLB patients are especially vulnerable to the antidopaminergic and anticholinergic actions of
most conventional antipsychotics, which makes treatment of the psychotic symptoms of DLB extremely
difficult. Patients are particularly sensitive to developing extrapyramidal symptoms (EPS)
and also to the potentially fatal complication of neuroleptic sensitivity, which affects ~50% of DLB
patients. Therefore, a need exists for antipsychotic drugs with less propensity to induce EPS and
reduced affinity for dopamine and acetylcholine receptors. Here we review studies evaluating the efficacy
and tolerability of atypical antipsychotics for the treatment of psychoses associated with DLB.
Olanzapine appears to be poorly tolerated, and risperidone has been associated with high risk of neuroleptic
malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic
action and risk of agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations
of DLB without causing neuroleptic sensitivity or increasing EPS. Hence, quetiapine is an
attractive candidate for the treatment of psychoses in DLB and other dementias.