ABSTRACT
We conducted prospective cognitive assessments over 14 +/- 6 (mean +/- SD) months of observation as part of the multicenter trial Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP), which involved 800 patients with early untreated Parkinson's disease. We administered tests that measured memory, visuospatial, and frontal lobe functions. Subjects were randomly assigned to receive placebo, deprenyl (10 mg/d), tocopherol (2,000 IU/d), or both deprenyl and tocopherol. We analyzed treatment effects using annualized rates of cognitive change. We performed exploratory analyses to identify potential clinical and demographic correlates of cognitive performance. There was no significant effect of either deprenyl or tocopherol on cognitive test performance. In early untreated Parkinson's disease, cognitive performance appears to be stable and unrelated to either motor deterioration or treatment with deprenyl or tocopherol.
Subject(s)
Cognition Disorders/drug therapy , Parkinson Disease/complications , Selegiline/therapeutic use , Vitamin E/therapeutic use , Aged , Cognition Disorders/etiology , Female , Humans , Male , Middle AgedABSTRACT
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.
Subject(s)
Clozapine/administration & dosage , Dyskinesia, Drug-Induced/drug therapy , Levodopa/adverse effects , Parkinson Disease/drug therapy , Aged , Clozapine/adverse effects , Disability Evaluation , Dose-Response Relationship, Drug , Drug Administration Schedule , Dyskinesia, Drug-Induced/diagnosis , Female , Humans , Levodopa/administration & dosage , Long-Term Care , Male , Middle Aged , Neurologic Examination/drug effects , Parkinson Disease/diagnosisABSTRACT
We gave increasing daily doses of clozapine to six patients with advanced Parkinson's disease (PD) and levodopa-induced dyskinesias. Clozapine reduced the daily dyskinesia time five-fold, increased "on" time eight-fold, and doubled the serum [DOPA] producing half-maximal dyskinesia. Parkinsonism scores after overnight DOPA withdrawal improved with increasing daily clozapine intake, and there was no clozapine dose-related shift in levodopa dose response for relief of parkinsonism. Patients experienced sedation, sialorrhea, and orthostatic hypotension. Clozapine appears to be an effective agent for suppression of levodopa-induced dyskinesias in PD.
Subject(s)
Clozapine/administration & dosage , Dyskinesia, Drug-Induced/drug therapy , Parkinson Disease/drug therapy , Aged , Clozapine/adverse effects , Dihydroxyphenylalanine/blood , Dose-Response Relationship, Drug , Female , Humans , Levodopa/adverse effects , Levodopa/therapeutic use , Male , Middle Aged , Parkinson Disease/blood , Parkinson Disease/complicationsABSTRACT
Dyskinesia is a recognized but uncommon side-effect of treatment with phenytoin. Two additional cases of dyskinesia during treatment with phenytoin are described; both had radiographically documented thalamic infarctions. The reported experience to date with movement disorders induced by phenytoin is reviewed and the clinical features summarized. The available experimental evidence addressing the mechanism underlying this side effect is discussed.
Subject(s)
Cerebral Infarction/complications , Dyskinesia, Drug-Induced/etiology , Epilepsy, Temporal Lobe/drug therapy , Phenytoin/adverse effects , Thalamic Diseases/complications , Aged , Cerebral Infarction/diagnosis , Dose-Response Relationship, Drug , Dyskinesia, Drug-Induced/diagnosis , Epilepsy, Temporal Lobe/diagnosis , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neurologic Examination/drug effects , Phenytoin/therapeutic use , Thalamic Diseases/diagnosis , Tomography, X-Ray ComputedABSTRACT
In six patients with advanced Parkinson's disease (PD), we have characterized the clinical responses and serum levels of DOPA and 3-O-methyldopa in response to continuous i.v., nasogastroduodenal (NGD), and oral (p.o.) administration of L-DOPA solution with concomitant suppression of peripheral decarboxylase activity by carbidopa. When compared to therapy with L-DOPA/carbidopa tablets, all patients experienced increased "on" and decreased "off" time with continuous L-DOPA intake. This improvement in mobility was accompanied by increases in duration and severity of dyskinesias. Serum levels of DOPA and 3-O-methyldopa were linearly related in ultrafiltered serum water compared to perchloric acid-treated serum samples, suggesting little protein binding. DOPA serum levels at which patients first turned "on" and those after several hours of continuous i.v. infusion clustered over a narrow range and were not predictable based on i.v. infusion rates, in spite of concomitant carbidopa intake. Continuous p.o. intake of L-DOPA solution produced serum levels of both DOPA and 3-O-methyldopa that were generally steady over the day and predictable based on L-DOPA intake rate. We conclude that "continuous" intake of L-DOPA solution orally, while cumbersome to and demanding of patients, can produce stable DOPA serum levels and approximate the improvement seen with continuous i.v. infusion. In our study, the apparent volume of distribution of L-DOPA was predictable with p.o. intake but not with i.v. administration of L-DOPA solution.
