MADRID – Rivastigmine should be the first option for treating dementia and associated behavioral symptoms in Parkinson's disease, with the atypical antipsychotics reserved for unresponsive patients, Dr. Murat Emre said at the 10th International Conference for Alzheimer's Disease and Related Disorders.
“There is evidence from our studies and from other, smaller studies that behavioral symptoms can improve with cholinergic treatment,” said Dr. Emre, a professor of neurology at the University of Istanbul (Turkey).
“If the symptoms are not massive, acute, or destructive, and are combined with dementia, the wise thing is to first try a cholinesterase inhibitor, because the atypical antipsychotics are associated with an increased risk of cerebrovascular or cardiovascular events.”
Up to 78% of Parkinson's patients eventually will develop dementia, Dr. Emre said. The prototypic syndrome consists of impaired or fluctuating attention and lessened visuospatial and executive function. There may be moderate memory impairment, although language is usually preserved. Depression, apathy, delusions, and hallucinations also can occur.
Clozapine and quetiapine are often prescribed for these symptoms in Parkinson's patients, Dr. Emre said. However, these drugs, like all atypical antipsychotics, carry a black box warning of increased mortality in elderly patients with dementia. The Food and Drug Administration, which reviewed 17 studies before issuing the warning, said most of the excess deaths were cardiovascular or infectious.
Because Parkinson's, like Alzheimer's, is a disease of the cholinergic system, cholinesterase inhibitors are a sound alternative for Parkinson's dementia, Dr. Emre said. Many small studies–all with fewer than 30 patients–have investigated the use of anticholinergics in Parkinson's dementia, concluding that the drugs can improve cognition without further impairing motor function. Only one large, placebo-controlled, randomized trial has addressed the issue, however.
That 2004 study by Dr. Emre and colleagues randomized 541 patients to either rivastigmine (titrated from 3 mg to 12 mg over 16 weeks) or placebo for 24 weeks. The trial found significant improvements in cognition, activities of daily living, and clinical impression among the active group, compared with the placebo group (N. Engl. J. Med. 2004;351:2509–18).
There were significantly more adverse events in the group on active treatment than in the placebo group, most of which were mild to moderate gastrointestinal upset. However, 10% of patients on active treatment did experience new or worsening tremor.
A 12-month follow-up crossover trial assessed the long-term effects of the drug. Published this year, the study concluded that rivastigmine maintained efficacy over time in the original group on active treatment, and that placebo patients switched to the drug showed improvements similar to those seen in the trial's initial group on active treatment (Mov. Disord. 2006;21:456–61).
However, the lag time for the original placebo patients did affect their improvements.