Behavioral Dysfunction

The Parkinson's-Reversing Breakthrough

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Dopaminergic and Serotoninergic

Classical antipsychotic drugs that potently block dopaminergic receptors can ameliorate psychotic symptoms but worsen parkinsonism, at times seriously enough to require levodopa (84). Better results in treating psychosis have been obtained with the atypical neuroleptics, possibly owing to their predominant antiserotoninergic rather than antidopaminergic activity. An extensive chart review revealed that 90% of DLB patients had partial to complete resolution of psychosis using long-term quetiapine, although in 27% motor worsening was noted at some point during treatment (85). A large, randomized blinded trial found that olanzapine (5 or 10 mg) reduces psychosis without exacerbating parkinsonism (86). Relatively small doses of clozapine have also been used successfully for the relief of paranoid delusions, psychosis, and agitation, albeit at the risk of agranulocytosis (84). Indeed, caution is generally warranted in using neuroleptics, since sedation, confusion, immobility, postural instability, and other serious side effects are hardly uncommon (87,88). Neuroleptic malignant syndrome (NMS) is a rare but fatal adverse effect more common with typical neuroleptics, such as haloperidol, owing to potent dopaminergic blockade (84,85). Dopaminomimetic agents (DA agonists more so than levodopa) are more likely to worsen than improve cognitive and affective function associated with the atypical parkinsonian disorders. The management of psychosis should thus first involve lowering the dose of anti-parkinsonian medication in this order: anticholinergics, amantadine, selegiline, DA agonists, and then levodopa; only if the improvement is inadequate, should a cautious trial of antipsychotic medication be considered (87). There are isolated reports of improvement in depression with levodopa (89), or with levodopa combined with L-threodihydroxyphenylserine and thyroid-releasing hormone (90). The successful use of clozapine in treatment-resistant psy-

Table 1

Most Commonly Recommended Drugs for Each Dysfunction

Most Commonly Recommended Drugs for Each Dysfunction

Table 1

Motor

Levodopa, variable response but best drug

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