Neurodegeneration underlies many brain disorders, including Alzheimer’s disease, Parkinson’s disease and Lewy body disease (LBD). LBD is now considered to be the second most common cause of dementia after Alzheimer’s disease. Post-mortem findings suggest LBD accounts for 15-25% of all dementia cases and is often underdiagnosed. While clinical diagnostic criteria for LBD continue to evolve, its characteristics include the dementia syndrome associated with fluctuations in cognition, perceptual abnormalities (of which visual hallucinations are most common) and mild parkinsonism. Other characteristic symptoms include frequent falls, nighttime agitation and depression. Clinical presentation of LBD could be partly understood in light of extensive destruction of dopaminergic and acetylcholinergic neurotransmitter systems by the underlying pathological process. Treatment of psychotic symptoms of LBD is difficult: patients are particularly sensitive to developing extrapyramidal symptoms (EPS), producing vulnerability to conventional antipsychotics’ side effects. Such sensitivity may in part be explained by antidopaminergic and anticholinergic profiles of most antipsychotics. The potentially fatal complication of neuroleptic sensitivity affects ~50% of LBD patients. A need exists for antipsychotic drugs with less propensity to induce EPS and reduced affinity for dopamine and acetylcholine receptors. Several studies suggest that atypical antipsychotics such as clozapine, risperidone, olanzapine and quetiapine may be able to treat psychoses associated with dementia.[1] Unlike other conventional or atypical agents, quetiapine has moderate affinity for D2 receptors, no appreciable affinity for acetylcholine receptors, and a placebo-level incidence of EPS across the whole dose range.[2] Quetiapine has been shown to reduce psychiatric manifestations of LBD without increasing EPS.[3] Olanzapine appears to be poorly tolerated in LBD patients[4] and risperidone use in LBD patients has been associated with high risk of neuroleptic malignant syndrome.[5] Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis.[6] Hence, quetiapine is an attractive candidate for treatment of psychoses associated with LBD and other dementias.
References
1. Kindermann SS, Dolder CR, Bailey A, Katz IR, Jeste DV. Pharmacological treatment of psychosis and agitation in elderly patients with dementia: four decades of experience. Drugs Aging 2002; 19: 257-276.
2. Arvanitis LA, Miller BG, and the Seroquel Trial 13 Study Group. Multiple fixed doses of ‘Seroquel’ (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry 1997; 42: 233-246.
3. Davis P, Baskys A. Quetiapine effectively reduces psychotic symptoms in patients with Lewy body dementia: an advantage of the unique pharmacological profile? Brain Aging 2002; 2: 49-53.
4. Walker Z, Grace J, Overshot R, Satarasinghe S, Swan A, Katona CL, et al. Olanzapine in dementia with Lewy bodies: a clinical study. Int J Geriatr Psychiatry 1999; 14: 459-466.
5. Ballard C, Grace J, McKeith I, Holmes C. Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer’s disease. Lancet 1998; 351: 1032-1033.
6. Juncos JL. Management of psychotic aspects of Parkinson’s disease. J Clin Psychiatry. 1999; 60 (Suppl 8): 42-53.
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