Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much more commonly, psychosis is induced by drug therapy for Parkinson's disease and is the strongest known risk factor for nursing home placement. Delusions are less frequent than hallucinations, but are more concerning as they are often paranoid in nature. Treatment begins with a search for correctable infectious, toxic, and metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications are slowly reduced. However, withdrawal of these drugs usually worsens parkinsonism and is often not tolerated. Certain atypical antipsychotics can be used to treat psychosis without compromising motor function. The choice of atypical antipsychotic is largely based on ease of use and adverse effect profile as most have comparable efficacy in improving psychosis. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not been reported in Parkinson's disease. The most common adverse effects of clozapine in Parkinson's disease are sedation, orthostatic hypotension and sialorrhoea. Sedation is generally helpful since these patients are frequently awake at night and tend to have worse behavioural problems then. Clozapine does not induce deterioration of motor function, but it has the potential to cause agranulocytosis, which is idiosyncratic and not dose-related. In risperidone-treated Parkinson's disease patients, reported adverse effects include somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium, fatigue, leg cramps, depression, urinary incontinence and hypotension. Although in some Parkinson's disease studies, risperidone has been well tolerated, others have shown that many patients are unable to tolerate the drug due to deterioration of motor function. While an initial study of olanzapine in Parkinson's disease psychosis showed the drug to be effective without deterioration of motor function, succeeding reports demonstrated a deleterious effect of the drug on motor functioning. The most common adverse effects of quetiapine in Parkinson's disease patients are sedation and orthostatic hypotension. There is a lack of double-blind trials; however, cumulative reports involving >200 Parkinson's disease patients strongly suggest that quetiapine is well tolerated and effective. Unlike clozapine, it does not improve tremor and may induce mild deterioration of motor function. Recently, cholinesterase inhibitors have been reported to alleviate psychosis in Parkinson's disease. Although ondansetron, an antiemetic with antiserotonergic properties, has been reported to relieve psychosis in Parkinson's disease, its prohibitive cost has prevented further study in this population. Electroconvulsive treatment is generally reserved for the patient with psychotic depression who is unable to tolerate any pharmacological therapy.
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PMID:Treatment of psychosis in Parkinson's disease: safety considerations. 1281 32

Atypical antipsychotics will continue to be prescribed for the behavioral symptoms of dementia in the absence of more effective, better tolerated, and safer alternatives. The evidence base, although incomplete, suggests that modest treatment effect sizes are offset by risk of considerable adverse effects. How might this information be best applied to clinical practice? Non-pharmacologic strategies should be implemented in routine clinical practice. Placebo-controlled clinical trials of individual antipsychotic agents have historically reported high placebo response rates; CATIE-AD reported that the sum total of the risk/benefit equation of atypical antipsychotic therapy was no greater than that achieved by placebo. CATIE-AD was designed to study the effectiveness of atypical antipsychotic treatment in community dwelling patients with AD. It is uncertain whether the results can be generalized to the populations of dementia patients residing in nursing homes with more severe cognitive and behavioral impairment. There is some suggestion that nursing home patients with dementia complicated by severe behavioral symptoms, particularly agitation and aggression without accompanying psychosis, might achieve greater benefit from atypical antipsychotic treatment than patients with milder behavioral symptoms. The finding that dementia patients without psychosis may respond more robustly to antipsychotic treatment seems counterintuitive, but may support the hypothesis that the neurobiology of the "psychosis of AD" differs from the psychosis of schizophrenia or bipolar disease. Adverse effects associated with antipsychotic therapy should be aggressively monitored throughout therapy. Treatment-emergent sedation was associated with all of the atypical antipsychotics in CATIE-AD and is probably an important mediator of mortality risk in patients with dementia. Sedation exacerbates pre-existing cognitive impairment and increases the risk of complications such as aspiration pneumonia, so concomitant use of benzodiazepines should be discouraged or limited to short periods with careful observation.' Once initiated, the effectiveness and tolerability of antipsychotic therapy should be evaluated routinely. In Alzheimer's disease, the severity and frequency of behavioral symptoms often decreases as illness progresses. In a stable patient, it is prudent to attempt to taper and discontinue the antipsychotic after 2-8 months of therapy. Better understanding of the potential adverse effects of antipsychotic therapy has increased interest in the effects of the dementia-specific medications on behavioral symptoms. Reductions in neuropsychiatric symptoms have been reported from trials of individual cholinesterase inhibitors, memantine monotherapy, and memantine combined with donepezil in AD patients. Studies of small numbers of patients in open trials of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and one double-blind placebo controlled trial (rivastigmine) have reported varying degrees of improvement of behavioral symptoms and psychosis of dementia with Lewy bodies (DLB). Delusions, hallucinations, apathy, and agitation/aggression are cited as the symptom categories most likely to show significant improvement. Since few of these studies were prospectively designed to study behavioral symptoms, results must be interpreted cautiously. Treatment of behavioral symptoms in AD and other dementias is challenging. The limitations of current approaches drive the search for effective, well tolerated therapies.
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PMID:Atypical antipsychotics for the treatment of dementia-related behaviors: an update. 1763 94