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)

Pergolide is a potent dopamine agonist and is known to have anti-Parkinson properties. We administered pergolide to patients with suboptimal control of Parkinson's disease who had a short-duration response to carbidopa-levodopa in a 6-month, double-blind study. Pergolide added to the carbidopa-levodopa regimen resulted in both subjective and objective improvement in comparison with placebo. In patients who tolerated pergolide, the median time spent in the "off" (parkinsonian) state was reduced from 5.0 to 2.2 hours daily (compared with a 0.3-hour reduction in the placebo group). These patients were able to decrease the median frequency of carbidopa-levodopa dosage from 7.5 to 5.0 doses daily (no change in the placebo group). Prolongation of the "on" response (optimal response to treatment) to single doses of drugs was corroborated by monitoring of the patients' Parkinson response cycle. The peak response was also improved in most patients. Of 25 patients randomized to the pergolide group, 7 were unable to tolerate this drug; confusion or hallucinations occurred in 4 of these patients, and chest pain, leukopenia, and nonspecific dizziness, respectively, developed in the other 3. All adverse events were reversible with reduction of the dose or discontinuation of the pergolide regimen. In conclusion, patients with Parkinson's disease who experience clinical fluctuations with carbidopa-levodopa may be helped by the addition of pergolide to the therapeutic regimen.
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PMID:Treatment of Parkinson's disease with pergolide: a double-blind study. 305 Mar

Previous short-term studies have shown that the dopamine agonist pergolide improves control of Parkinson's disease when used in conjunction with carbidopa-levodopa (Sinemet). We assessed the long-term outcome (2 1/2- to 3-year follow-up) in patients with Parkinson's disease who participated in our previous pergolide double-blind trial and were subsequently switched to open-label pergolide therapy. Of 41 evaluable patients who began pergolide therapy, 10 (24%) experienced sustained substantial benefit that persisted to the end of this investigation. A total of 23 patients (56%) remained on pergolide therapy and, as a group, had considerable improvement over baseline at 2 1/2 to 3 years on the basis of several measurements of efficacy. A tendency toward deterioration could be reversed in many patients by larger or more frequent doses of carbidopa-levodopa; nevertheless, all but four patients were still taking the same dose or less of carbidopa-levodopa at the end of this study as at the onset. Patients with the best initial response to pergolide seemed most likely to experience long-term benefit. Confusion and hallucinations were the side effects most likely to necessitate discontinuation of pergolide. Symptoms suggestive of dose-related angina pectoris occurred in four patients in the open-label phase and two patients in the earlier double-blind phase (13% of patients who started pergolide therapy); these symptoms were easily controlled by dose reduction or discontinuation of pergolide, without sequelae. Dose-related leukopenia developed in one patient.
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PMID:Pergolide: long-term use in Parkinson's disease. 305 Mar 1

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

Four open-label studies have reported beneficial effects of clozapine on the tremor of idiopathic Parkinson's disease (PD). We performed a double-blind crossover trial with a 2-week washout, comparing low-dose clozapine to benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and 19 completed the study. Benztropine and clozapine were equally effective in improving tremor and the motor score of the United Parkinson's Disease Rating Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse events were experienced with each drug, but leukopenia was not encountered. We conclude that the atypical antipsychotic drug clozapine is helpful in the treatment of tremor in PD and should be considered when all other drug therapies fail.
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PMID:Benztropine versus clozapine for the treatment of tremor in Parkinson's disease. 910 3

Psychotic disorders in the elderly are frequent, of multiple etiologies, and little researched. With the advent of "atypical" neuroleptics, their role in treating elderly psychiatric patients needs to be investigated. Clozapine is widely used; however, its use is common in the elderly whose psychosis is a feature of neurological morbidity (Parkinson's disease, dementia, etc.), making it difficult to ascertain the safety, tolerability, and efficacy in psychiatric disorders in late life. The aim of the present review is to evaluate clozapine's effect in elderly psychiatric patients with no neurological comorbidity. A computerized literature search (MedLine 1966 to 1997) revealed 133 patients fulfilling said criteria. Fifteen patients had side effects and/or adverse events during treatment; nine of these were receiving a dosage greater than 100 mg clozapine daily. In 19 patients, treatment was discontinued, three due to noncompliance and 16 due to side effects. In seven patients, leukopenia/agranulocytosis was reported. The majority of side effects (27 of 34) and treatment discontinuations were within the first 90 days of treatment. Although efficacy is difficult to compare across studies because of differing methods of evaluation, the great majority of patients showed moderate to marked improvement of psychotic features. The reported effectiveness in patients able to continue treatment for extended periods is significant. Thus, clozapine at a relatively low mean dose (134 mg daily) seems to be safe, tolerated, and effective in elderly psychiatric patients. Agranulocytosis is more frequent than in younger adults and should be monitored carefully.
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PMID:Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy. 1042 93

Parkinson's disease (PD) is a progressive neurodegenerative disorder with both motor and nonmotor symptoms (NMS), leading to significant morbidity and caregiver burden. Psychosis is common but is under recognized by physicians. When present, it increases the patient's risk of hospitalization and nursing home placement and caregiver burden. Although the atypical antipsychotic agent, clozapine, has been considered the gold standard treatment, severe agranulocytosis in 0.38% of patients and more commonly milder leukopenia, resulting in frequent blood testing, limit its use. Pimavanserin, a 5HT2A receptor inverse agonist, has been shown to reduce psychosis in PD without worsening motor symptoms. It is therefore a welcome therapeutic option for this devastating NMS.
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PMID:Evidence for the use of pimavanserin in the treatment of Parkinson's disease psychosis. 2780 22