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Levodopa

Motor symptoms contribute to the disability experienced by DLB and PD-D patients and are associated with an increased risk of falls. Acute levodopa challenge in 14 DLB patients yielded some improvement in UPDRS III score, finger tapping, and walking test, but less so than in PD or PD-D [121, 122]. Of the DLB patients, 36% were classified as ‘responders’ on levodopa challenge, compared with 70% of the PD-D and 57% of the PD patients. Although the majority of DLB patients seemed to tolerate the drug, 15% withdrew due to confusion and gastrointestinal problems. In an extension of this study [122], acute levodopa challenge considerably improved motor function and subjective alertness in all patients, without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Moreover, neuropsychiatric scores improved in patients with PD (both with and without dementia) on levodopa at 3 months. Sleep disturbances and VH are possible adverse effects of treatment with levodopa. Because of the common presence of these symptoms in untreated DLB there is a theoretical risk that VH and sleep disturbances may appear or be exacerbated in DLB patients with levodopa treatment. However, a study examining sleep disturbances and excessive daytime sleepiness suggest that levodopa treatment does not worsen such symptoms [123]. Conversely, in a prospective study of 19 DLB patients limited efficacy and increased risk for psychosis was observed in DLB during 3 months of levodopa treatment [124]. Overall it would therefore appear that DLB patients are less responsive to levodopa than people with PD-D, but the relative impact on neuropsychiatric symptoms and cognition remains unresolved. Treatment with dopamine receptor agonists is a feasible alternative to levodopa therapy in PD. However, dopamine receptor agonists are known to provide a higher risk for VH and sleep attacks in PD than does levodopa; therefore their use in patients with DLB is not recommended [125].

Primavanserin is a selective serotonin 5-HT2A inverse agonist without dopaminergic effects. Since VH and delusions in LB disease and some other neurodegenerative disorders have been linked to dysfunction in the serotonin system, primavanserin has been proposed as a possible treatment for these symptoms. In a recent trial, primavanserin showed improvement in psychotic

 
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