Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychosis secondary to dopaminergic therapy can limit the ability to manage motor symptoms of advanced Parkinson's disease (PD). We report the results of an open label 3-month trial that evaluated the antipsychotic effects of clozapine in eight PD patients with drug-induced psychosis. Response was quantified using a simplified brief psychiatric rating scale and two PD scales. Clozapine significantly improved psychiatric scores at low doses. The use of every other day regimens (not previously utilized) led to good control of symptoms and minimized side effects. Clozapine also had a positive sleep effect in four patients and improved dyskinesia in one. Finally, this treatment prevented recurrence of psychosis while levodopa doses were significantly increased and while other antiparkinsonian medications were added. Motor disability related to PD improved as a result of these treatment adjustments. We conclude that clozapine is effective in treating drug-induced psychosis in PD and allows for safe optimization of antiparkinsonian therapy.
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PMID:Clozapine prevents recurrence of psychosis in Parkinson's disease. 135 59

While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of "normality," which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.
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PMID:Optimization of levodopa therapy. 154 99

The clinical efficacy of clozapine, an atypical antipsychotic, in treating levodopa-induced hallucinations was investigated in five patients with Parkinson's disease under open label conditions. Two patients could not tolerate clozapine, even in doses as low as 12.5-25 mg daily, because of extreme sedation. Three patients could tolerate clozapine and experienced improvement or elimination of their hallucinations at doses below 100 mg daily. Despite a significant risk of adverse effects, cautious use of clozapine in low doses may be beneficial for patients with levodopa-induced psychosis who do not respond to more conservative measures.
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PMID:Clozapine for psychosis in Parkinson's disease. 238 41

A total of 13 patients with drug-induced psychosis in Parkinson's disease were treated with two non-classical neuroleptics-clozapine and fluperlapine. Patients mainly complained about severe hallucinatory symptoms and different degrees of paranoid delusions. Complete relief was observed in 8 patients, moderate improvement in 3 and no effects in 2. Parkinsonian disability did not increase under neuroleptic medication with clozapine and fluperlapine, but could be ameliorated by additional L-dopa or bromocriptine medication. The non-classical neuroleptics employed are dopamine D2 blocking agents with a preferential binding to mesolimbic, mesocortical and hippocampal D2 receptors and no substantial binding to striatal dopamine receptors. Restricted use of these two neuroleptics is necessitated because of the danger of agranulocytosis.
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PMID:Treatment of drug-induced exogenous psychosis in parkinsonism with clozapine and fluperlapine. 286 54

Drug-induced psychosis is a serious late complication of Parkinson's disease (PD) that requires aggressive treatment. Recent studies have found clozapine a highly effective and ECT a possibly useful intervention. Two cases are presented that illustrate a possible treatment role for ECT. The cases demonstrate that ECT has significant but short-lived antipsychotic effects when used alone. However, patients who do not respond to clozapine monotherapy can be given adjunctive treatment with ECT. The combination therapy resulted in abrupt alleviation of psychotic symptoms in one of the cases, and maintenance with low-dose clozapine allowed for long-term efficacy. On the basis of these findings, a therapeutic approach to patients with drug-induced psychosis in PD is suggested.
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PMID:Combined clozapine and electroconvulsive therapy for the treatment of drug-induced psychosis in Parkinson's disease. 758 Jan 88

The purpose of this study was to determine the plasma level of clozapine and its metabolite, N-desmethylclozapine, in Parkinson's disease patients with L-DOPA-induced psychosis responsive to clozapine. The psychotic symptoms of the three patients studied responded to low doses of clozapine with plasma levels of clozapine between 4.5 and 16.1 ng/ml and N-desmethylclozapine between 2.6 and 6.1 ng/ml, much below the plasma clozapine levels usually found in clozapine-treated refractory schizophrenia or affective disorders (range 100 to 687 ng/ml). Possible mechanisms that may account for clozapine's antipsychotic action in dopaminomimetic-induced psychosis in Parkinson's disease, including serotonin2A (5-HT2A) and dopamine D4 receptor blockade, at plasma levels that would be ineffective in refractory schizophrenia, are discussed. It is suggested that 5-HT2A receptor blockade is the most likely basis for the effectiveness of clozapine in L-DOPA psychosis.
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PMID:Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson's disease. A high potency effect of clozapine. 776 85

We evaluated the effects of mianserin, a relatively selective 5-HT2 receptor antagonist, on symptoms related to drug-induced psychosis in patients with Parkinson's disease (PD). A total of 12 patients with PD who had developed drug-induced psychosis showed delirium (DSM-III-R criteria; n = 10) and pure visual hallucinations (n = 2). The antiparkinsonian drugs involved in the drug-induced psychosis were L-DOPA/carbidopa, bromocriptine, trihexyphenidyl, and amantadine. They received mianserin (mean 36.7 mg, range 20-60 mg) given orally for 8 weeks. Complete relief or marked improvement in psychotic symptoms was noted in 8 patients, moderate improvement in 2 patients, and no effect in 2 patients. The parkinsonian disability also decreased slightly in 8 patients. These results suggest that serotonin antagonism at 5-HT2 receptors may not only play an important role in the treatment of drug-induced psychosis in PD, but may also ameliorate the symptoms of parkinsonism.
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PMID:Mianserin treatment of patients with psychosis induced by antiparkinsonian drugs. 777 16

This article reviews new medical and surgical treatments for Parkinson's disease (PD). Catechol-O-methyl-transferase (COMT) inhibitors supplement the variety of antiparkinsonian drugs interacting with the dopaminergic system. Clinical studies show that COMT inhibitors prolong the action of levodopa in patients with the "wearing off" phenomenon. The atypical antipsychotic drug clozapine is the treatment of choice for the alleviation of levodopa-induced psychosis. Clozapine also has beneficial effects on tremor and levodopa-induced dyskinesias. Thus, COMT inhibitors and clozapine provide new opportunities for the treatment of patients with longstanding PD and fluctuating responses to levodopa. Experimental evidence in animals suggests that glutamate antagonists have symptomatic and neuroprotective actions in PD. At present, however, only weak antiglutamatergic drugs that have low specificity, such as memantine, amantadine, and budipine are available for clinical studies. Neurotrophic factors, in particular ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, are among the most promising new approaches for neuroprotection in PD. Problems of bioavailability, however, thus far preclude their use in patients. An improved understanding of the pathophysiology of parkinsonism has led to a renaissance of stereotaxic surgery. The subthalamic nucleus is a potential new target for surgical intervention. Ventroposterior pallidotomy has been shown to improve not only rigidity and tremor, but also akinesia. The techniques for thalamic interventions have been refined by introducing chronic thalamic stimulation. Future transplantation approaches to PD will focus on the use of genetically modified cells carrying genes for dopamine-synthesizing enzymes or neurotrophic factors. Animal studies show the feasibility of in vivo gene transfer for the treatment of PD.
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PMID:New medical and surgical treatments for Parkinson's disease. 795 44

Current treatment strategies for levodopa-induced psychosis in Parkinson's disease have had limited success. Remoxipride, a selective D2 receptor antagonist, was administered in an open label pilot study to seven parkinsonian patients exhibiting thought disorder. Symptoms improved significantly in six patients after treatment durations of 1-6 months and cleared completely in two individuals. One patient (at age 90 the oldest in the group) could not tolerate the compound due to significant motor deterioration, and the drug had to be discontinued after 1 week. In all remaining patients, no motor complications appeared, and therapeutic effects of remoxipride continued for up to 3 months after treatment cessation and have lasted for 2 years now in one individual. Further study of this compound in the context of treatment-induced psychosis in Parkinson's disease appears to be warranted.
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PMID:Symptomatic relief from treatment-induced psychosis in Parkinson's disease: an open-label pilot study with remoxipride. 819 83

Psychosis secondary to dopaminergic therapy can limit the ability to manage motor symptoms of advanced Parkinson's disease (PD). Scholz and Dichgans (1985) were the first to report the use of clozapine in drug-induced psychosis in PD. The rationale for use of clozapine in parkinsonian patients is supported by his original pharmacological profile with weak extra-pyramidal side effects. A Medline search was performed of literature from 1985 to 1994. The literature search was not limited to the English language. Numerous authors (23 articles) using case reports or open trials among more than 100 patients suggested that clozapine would be useful in treating drug-induced psychosis in PD. We analysed the available information addressing: 1) clinical efficacy, 2) clinical predictors of outcome, 3) delay of action, 4) influence of clozapine on extrapyramidal symptomatology, 5) adverse effects and treatment withdrawal causes, 6) long-term follow-up data. However, the partially negative result of the only double-blind placebo-controlled trials, it may be stated that in some clinical situation of psychosis in PD, the use of clozapine may represent an opportune alternative when other therapeutic strategies have failed.
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PMID:[Value of clozapine in treatment of psychotic disorder in Parkinson disease]. 868 76


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