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)

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

Tremor at rest is a classic symptom of Parkinson's disease that causes significant disability and distress for the patient and is generally only weakly responsive to conventional treatment, like anticholinergic and dopaminergic medication. This study describes the treatment with Clozapine in patients with Parkinson's disease, who despite optimal antiparkinson medical therapy still have a major disabling tremor at rest. Clozapine is an "atypical" neuroleptic agent, producing fewer extra pyramidal side effects common to conventional antipsychotic drugs. Clozapine, however, has as its most serious complication agranulocytosis, and hence all patients taking Clozapine must undergo blood tests at least several times a month. Under these frequent blood monitoring conditions, in this study Clozapine produced a substantial alleviation of parkinsonian tremor in 17 of 23 patients (73%). The beneficial response was reached with a relative low dose of Clozapine (18 mg./day), while previous antiparkinson medication was kept unchanged. The improvement of tremor at rest was noticeable generally within 2 weeks of beginning Clozapine therapy. No tolerance to the antitremor efficacy of Clozapine was seen during study-period of at least 6 months. Leucopenia developed in one patient, other major adverse events were hypersalivation and day-time drowsiness. These findings confirm the substantial antitremor efficacy of Clozapine in Parkinson's disease.
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PMID:Clozapine in the treatment of tremor in Parkinson's disease. 779 42

Parkinson's disease (PD) patients and their normal controls performed two experiments involving a sequential movement task, depressing a series of buttons at choice points along a response board. Visual or auditory cues were presented prior to each move according to various contingencies. PD, a disorder characterised by degeneration of the basal ganglia (BG), typically manifests with poor execution of motor sequences. We found that external cueing facilitated motor sequencing in PD patients. In particular, auditory cues which occurred late in the movement cycle maximally facilitated switching between subcomponents of a sequence. Based on physiological findings reported in the primate literature [Brotchie et al., Brain 114, 1685-1702, 1978; Schultz and Romo, Exp. Brain Res. 1, 363-384, 1992], it is suggested that external cues enhance performance by replacing defective, internally generated cues (discharges) of the BG. This has implications for the use of physical training strategies in the treatment of PD.
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PMID:Contingent and non-contingent auditory cueing in Parkinson's disease. 855 24

Levodopa-induced dyskinesias result in considerable functional impairment for patients and formidable therapeutic challenges for physicians. A practical method of treating such dyskinesias is first to classify the levodopa dyskinesias according to their temporal profile after drug administration, namely, into predictable (interdose, biphasic and 'off-period') and unpredictable ('on-off') dyskinesias. Treatment of each type of dyskinesia requires a different and relatively specific therapeutic strategy. With progression of Parkinson's disease, the threshold for interdose dyskinesia lowers, while the threshold for antiparkinsonian efficacy is unchanged; therefore, the strategy is to maintain levodopa concentrations between these 2 thresholds and avoid high concentrations. Frequent small doses of liquid levodopa preparations may be indicated. Clozapine appears to increase the threshold for dyskinesia. However, its usefulness is limited primarily by dose-related sedation and by dose-unrelated agranulocytosis. Buspirone and fluoxetine may have specific antidyskinetic benefit. Surgical treatment may aid selected patients, although criteria for selection are not fully established. The biphasic dyskinesias occur just before and just after an oral dose of levodopa. They result when levodopa concentrations fall below or rise above the threshold for therapeutic efficacy; therefore, the strategy is to maintain concentrations as nearly constant as possible above that threshold. Dopamine agonists such as subcutaneous apomorphine combined with domperidone may be particularly helpful. Thalamic stimulation can also benefit selected patients. 'Off-period' dyskinesias occur at times of predicted low concentrations of levodopa. The treatment strategy is to provide sufficient levodopa or dopaminergic stimulation during those intervals. Dopamine agonists (e.g. bromocriptine at night) may help the characteristic early foot dystonia. Anticholinergic agents may also help. The unpredictable ('on-off') dyskinesias are first analysed to establish a pattern of response. Then, on the basis of that pattern, they are treated by maintaining levodopa concentrations or dopaminergic tone during the periods that would ordinarily be 'off.' Administration of liquid levodopa preparations, addition of dopaminergic agents, restriction of treatment during the morning hours as well as restriction of the majority of dietary protein in the evening meal may provide a period of predictable good function early in the day. Clozapine, even early in treatment, appears to reduce the incidence of these dyskinesias. Rescue with apomorphine during a malignant prolonged 'off' phase is particularly valuable.
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PMID:Methods of managing levodopa-induced dyskinesias. 882 14

The occurrence of psychosis is frequent during the evolution of Parkinson's disease. The reduction of therapeutics or the use of classical neuroleptics may improve the symptoms, but usually worsens parkinsonism. Clozapine is an atypical neuroleptic with only few extrapyramidal effects, which has been proposed at low dose in this indication since 1985. A review of the literature, about more than 200 patients shows good results in approximately 90% without worsening of extrapyramidal symptoms. Some patients even noted an improvement of their motor state while treated by clozapine alone or as dopatherapy was secondarily increased. More controversial results were obtained in demented or depressed patients. Sedation is one of the most frequently encountered side-effect but rarely necessitates the withdrawal of clozapine. Even if the risk of agranulocytosis is slight, regular blood cell counts must be done.
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PMID:Clozapine for the treatment of psychosis in Parkinson's disease: a review. 894 85

Dopaminergic psychosis frequently complicates the pharmacological treatment of Parkinson's disease. Dose reduction of dopaminomimetic therapy or treatment with conventional neuroleptics improves psychosis but worsens parkinsonism. In an open-label 12-month trial, the clinical antipsychotic efficacy of the atypical neuroleptic clozapine was investigated in 36 parkinsonian patients (age range 46-85 years) with symptoms of dopaminergic psychosis including delusions, vivid dreams, hallucinations, frank paranoid delirium, and hypersexuality. Clozapine, given orally at bedtime, was started at a dose of 6.25 mg and titrated upward to the minimal effective dose. In all patients, psychosis responded to very low clozapine doses (mean 10.59 +/- 6.48 mg/day). Clozapine doses correlated with the severity of psychosis. During clozapine treatment, parkinsonian disabilities and levodopa dosage remained statistically unchanged. During the 12-month study, no patient had clozapine-induced agranulocytosis or other severe side effects. These findings indicate that even at low doses, clozapine effectively controls dopaminergic psychosis in Parkinson's disease patients without compromising motor function.
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PMID:Low dose of clozapine in the treatment of dopaminergic psychosis in Parkinson's disease. 919 42

The atypical antipsychotic clozapine has been reported to be effective in otherwise refractory psychoses. This, and its low potential for inducing extrapyramidal side effects and tardive dyskinesia, predestines this drug for the treatment of psychotic disorders in late life. However, not much is known about the efficacy, safety and pharmacokinetics of clozapine in the treatment of aged patients. There are some studies and reports available about clozapine in the treatment of psychosis in patients suffering from dementia, schizophrenia and Parkinson's disease, which are reported here. They give some evidence that even low doses of clozapine are effective in controlling psychotic symptoms in the elderly. To avoid side effects, patient-specific factors and changes of pharmacokinetics in the elderly have to be considered. However, side effects including sedation, delirium, posturnal hypotension and the risk of agranulocytosis in particular limits the use of clozapine in elderly patients.
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PMID:[Clozapine in treatment of neuropsychiatric diseases in the elderly]. 937 47

Clozapine is a novel antipsychotic agent used in the treatment of schizophrenic patients who have not responded to or have been unable to tolerate conventional neuroleptic therapy. In this paper, the literature surveying the uses of clozapine in the treatment of patients with nonschizophrenic illnesses, in particular psychotic affective disorders (bipolar disorder and schizoaffective disorder), will be reviewed. (A Medline search was done for all papers concerning clozapine; those that represented major contributions to the literature were used.) Results from a prospective study at McLean Hospital assessing the effects of diagnosis on response will be presented. Several other uses in nonschizophrenic patients will also be discussed. Because of its relative freedom from extrapyramidal side effects, it is an important agent in the treatment of patients with Parkinson's disease who also have psychotic symptoms. It may be effective in the treatment of tardive dyskinesia in nearly 50% of patients with that symptom. In addition, the drug may be useful in treating violent patients and those with certain movement disorders, atypical borderline personality disorder, or chronic psychotic symptoms. Due to the risk of agranulocytosis, clozapine cannot yet be considered a first-choice treatment for psychotic symptoms, but many studies indicate it to be helpful with a wide variety of treatment-resistant ones.
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PMID:Uses of clozapine in nonschizophrenic patients. 938 95

Psychosis induced by the standard drugs for treating idiopathic Parkinson's disease (PD) occurs, in the long term, in approximately 5-8% of patients. Until the development of atypical antipsychotic drugs, treatment of this psychosis was extremely limited and unsatisfactory. Clozapine has been reported to be an effective and well-tolerated treatment for this problem. Clozapine, however, is a difficult drug to use as a result of the monitoring system mandated by the Food and Drug Administration because of the potential for agranulocytosis. Treatment with risperidone has been shown to be poorly-tolerated. This article reports on the authors' open label experience with the newest atypical antipsychotic, olanzapine, and the switching of stable patients from clozapine to olanzapine. Nine of twelve subjects were unable to make the transition because of worsened parkinsonism. Most subjects preferred taking clozapine, despite the onerous monitoring procedure.
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PMID:Substituting clozapine for olanzapine in psychiatrically stable Parkinson's disease patients: results of an open label pilot study. 978 8

Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.
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PMID:Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease. 1034 74


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