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)

Dyskinesias commonly appear during L-dihydroxyphenylalanine (L-DOPA) therapy of advanced Parkinson's disease (PD) and can occur in both dose-related and dose-independent patterns. Clozapine exerts a dose-related suppression of L-DOPA-induced dyskinesias by shifting the i.v. L-DOPA dose-response curve for production of dyskinesias without altering relief of parkinsonism. We report our outpatient experience with 13 patients on daily clozapine therapy (maximum dose 400 mg/day), followed for 3-21 months (median 10). Beneficial effects of clozapine, determined from twice-weekly diaries, included increased "on time" and decreased "off time" and time "on with dyskinesia." Improvements were statistically apparent by 75 mg/day and remained so through 200 mg/day. Sedation was a common problem, reflected by increased time "asleep" which was significant by 50 mg/day. Sedation was dose limiting in most patients. Orthostatic hypotension and sialorrhea were variably present. No patients had seizures, bone marrow toxicity, or detectable loss of efficacy of clozapine with chronic use. We conclude that clozapine is an effective agent for suppression of dyskinesias in PD with an effective daily dose for most patients of 100-200 mg/day.
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PMID:Suppression of dyskinesias in advanced Parkinson's disease: moderate daily clozapine doses provide long-term dyskinesia reduction. 796 7

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

Patients with essential tremor (ET) may not respond to commonly used drugs. Clozapine, an atypical neuroleptic drug, has been reported to improve postural Parkinson's disease tremor clinically resembling ET. The effects of a single dose of 12.5 mg clozapine and placebo were evaluated in a randomized, double-blind, crossover study in 15 drug-resistant patients with ET. Patient responders with more than 50% improvement after a single dose of clozapine subsequently received the drug (39+/-9 mg up to 50 mg) unblinded for a period of 15.8+/-7.7 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients (p <0.01). Sedation was the only side effect reported during the clozapine test; however, the time course of sedation and of the antitremor effect were not coincident. A significant reduction of tremor was reported with chronic clozapine treatment (p <0.01) with no tolerance to drug antitremor effect, whereas sedation markedly decreased after 6-7 weeks of therapy. No clozapine-induced hematologic side effects were observed in our cohort of patients during long-term treatment. Our results suggest that in selected drug-resistant ET cases, clozapine should be considered before resorting to neurosurgical options.
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PMID:Acute and chronic effects of clozapine in essential tremor. 1034 71

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

This manuscript reviews apomorphine administration in formulations other than intermittent bolus injection, and comments on other potential uses for this unique compound. Continuous sc apomorphine therapy has been shown to alter peak-dose dyskinesia thresholds in advancing patients, and in some instances may replace all other anti-parkinson therapies. In general continuous infusion of sc apomorphine at a rate of 4 mg/h is well tolerated, and has been postulated to be equivalent to approximately 600 mg levodopa/day. This therapy is associated with skin complications, particularly nodule formation, and focal panniculitis is seen in more than 50% of subjects. Optimal dosages for intranasal apomorphine range from 2 to 5 mg per inhalation with benefit seen at 7.5 minutes and duration of effect of 45 to 55 minutes. Side effects included nasal irritation, vestibulitis, dyskinesias, yawning, and nausea. Comparison of 3 mg sc and 30 mg sublingual apomorphine in 9 Parkinson's disease subjects in a blinded cross-over trial found that the time to peak benefit was beyond 40 minutes with sl apomorphine, compared to 21 minutes in the sc preparation. Chronic use of the sublingual formulation was associated with severe stomatitis in half the subjects, and markedly limited the treatment. Rectal administration of apomorphine has been evaluated in limited, usually post-operative settings. Administration of a 200 mg apomorphine rectal suppository resulted in an average time to benefit of 32 minutes with an average duration of 195 minutes. Sedation, nausea and faintness were reported as side effects. Although the diagnostic confirmation potential of this agent has been questioned, the drug may have an important role in evaluating the potential for benefit in the deep brain stimulation surgical setting.
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PMID:Other formulations and future considerations for apomorphine for subcutaneous injection therapy. 1503 68

Magnetic resonance-guided focused ultrasound thalamotomy is an innovative minimally invasive treatment for medication-resistant tremor in patients with essential tremor and Parkinson disease. Sedation with common hypnotic agents is discouraged because the patient's cooperation is required during the procedure, and these drugs interact with the patient's tremor, interfering with the results of intraprocedural neurological evaluations. Dexmedetomidine may be the best choice for sedation during magnetic resonance-guided focused ultrasound thalamotomy, which can be prolonged and poorly tolerated by the awake patient. We report the first use of dexmedetomidine for sedation in magnetic resonance-guided focused ultrasound thalamotomy in 3 patients: none of them experienced relevant hemodynamic changes or apnea.
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PMID:Dexmedetomidine Sedation in Magnetic Resonance-Guided Focused Ultrasound Thalamotomy: A Case Series of 3 Patients. 3116 70

Magnetic resonance-guided focused ultrasound thalamotomy is an innovative minimally invasive treatment for medication-resistant tremor in patients with essential tremor and Parkinson disease. Sedation with common hypnotic agents is discouraged because the patient's cooperation is required during the procedure, and these drugs interact with the patient's tremor, interfering with the results of intraprocedural neurological evaluations. Dexmedetomidine may be the best choice for sedation during magnetic resonance-guided focused ultrasound thalamotomy, which can be prolonged and poorly tolerated by the awake patient. We report the first use of dexmedetomidine for sedation in magnetic resonance-guided focused ultrasound thalamotomy in 3 patients: none of them experienced relevant hemodynamic changes or apnea.
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PMID:Dexmedetomidine Sedation in Magnetic Resonance-Guided Focused Ultrasound Thalamotomy: A Case Series of 3 Patients. 3292 20