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)

Clozapine is the least likely anti-psychotic to induce extrapyramidal symptoms (EPS). We present a surprising case of a woman schizophrenic patient treated with clozapine suffering from EPS. Single photon emission computed tomography (SPECT) revealed a low density of presynaptic dopamine transporters in our patient's brain. A comorbid diagnosis of Parkinson's disease in schizophrenia was confirmed in this way. This helped us to find a proper therapeutic strategy for our patient.
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PMID:Comorbidity of parkinsonism and schizophrenia in a patient treated with clozapine. 1292 28

Psychotic symptoms are common and can be a major therapeutic challenge in patients with Parkinson's disease (PD). PD-related psychosis is usually characterized by visual hallucinations or delusions and is most often induced by antiparkinsonian medications. However, other medical conditions, psychoactive medications, sleep disturbances, mood disorders, and cognitive impairments are relevant risk factors. Patients with PD should be continually monitored for factors that can trigger the development of psychotic symptoms, including minor symptoms. This includes ongoing critical re-evaluation of the therapeutic regimen, with adjustments as indicated to optimize function across motor, cognitive, and psychiatric domains. Treatment strategies to reduce psychotic symptoms are determined by the clinical picture. "Benign" symptoms may require only education and reassurance. Antipsychotic medications are required for disabling symptoms and emergency hospitalization may be required for agitation that affects the safety of the patient or others. Medication management is often complex and includes elimination or reduction of antiparkinsonian agents (although this can compromise motor function), management of medical comorbidities, and use of atypical antipsychotics. Clozapine and quetiapine are regarded as the most safe and effective atypical neuroleptics in PD patients. Cholinesterase inhibitors can enhance cognition and may reduce psychotic symptoms.
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PMID:Psychosis in Parkinson's Disease. 1504 1

Clozapine is the gold standard treatment for Parkinson's disease (PD) psychosis based on double blinded, placebo controlled trials, and has also been shown to alleviate tremor and dyskinesia. There is accumulating data suggesting that clozapine may be associated with increased frequency of diabetes mellitus (DM) compared to conventional neuroleptic drugs in treating schizophrenia. Forty-four predominantly geriatric parkinsonian subjects on clozapine for psychosis, tremor or dyskinesia, on an average dose of 50.6 mg/d for a mean duration of 41 months were reviewed. The prevalence of DM in this cohort was 18.1% (8/44). This rate was similar to that reported in the aged-matched general population (prevalence = 19.3% for ages > or = 60 years). In this small study, parkinsonian patients on long-term, low dose clozapine were not at increased risk for developing DM. Larger controlled prospective studies are needed to confirm this.
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PMID:Diabetes mellitus among parkinsonian patients treated chronically with clozapine. 1546 3

Parkinson's disease is associated with classical Parkinsonian features that respond to dopaminergic therapy. Neuropsychiatric sequelae include dementia, major depression, dysthymia, anxiety disorders, sleep disorders, and sexual disorders. Panic attacks are particularly common. With treatment, visual hallucinations, paranoid delusions, mania, or delirium may evolve. Psychosis is a key factor in nursing home placement, and depression is the most significant predictor of quality of life. Clozapine may be the safest treatment for psychotic features, but more research is needed to establish the efficacy of antidepressant treatments. Dementia with Lewy bodies, the second most common dementia in the elderly, may present in association with systematized delusions, depression, or RBD. Early evidence suggests the utility of rivastigmine, donepezil, low-dose olanzapine, and quetiapine in treating DLB. Parkinson-plus syndromes generally lack a good response to dopaminergic treatment and evidence additional features, including dysautonomia, cerebellar and pontine features, eye signs, and other movement disorders. MSA is associated with dysautonomia and RBD. SND (MSA-P) is associated with frontal cognitive impairments, but dementia, psychosis, and mood disorders have not been strikingly apparent unless additional pathological findings are present. In SDS (MSA-A), impotence is almost ubiquitous; urinary incontinence is frequent; depression is occasional, and sleep apnea should be treated to avoid sudden death during sleep. OPCA neuropsychiatric correlates await further definition. Progressive supranuclear palsy neuropsychiatric features include apathy, subcortical dementia, pathological emotionality, mild depression and anxiety, and lack of appreciable response to donepezil. CBD usually is recognized by early frontal dementia with ideomotor apraxia, often in the right upper extremity, attended later by poorly responsive unilateral Parkinsonism, with additional signs including cortical reflex myoclonus, limb dystonia, alien limb, oculomotor apraxia when asked to look horizontally, depression, personality changes, and, occasionally, Kluver-Bucy syndrome. The neuropsychiatry of FTDP-17 involves apraxia, executive impairment, personality changes, hyperorality, and occasional psychosis. Future research in these Parkinsonian disorders should target the characterization of neuropsychiatric sequelae and their treatment.
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PMID:The neuropsychiatry of Parkinson's disease and related disorders. 1555 Feb 93

Clozapine was one of the major advances in the treatment of schizophrenia since the introduction of the classic antipsychotic agent chlorpromazine in the 1950s. Over the past 10 years, clozapine has become the reference compound for the development of new antipsychotics, and new drugs have been developed which have also claimed atypical status. The indications of clozapine were recently extended to Psychosis in Parkinson's disease and harmonized in the European Union. This provides the opportunity to update the data on clozapine in the treatment of schizophrenia. In this article we review current clinical evidence in schizophrenia to address the following issues: 1) Efficacy in refractory/positive symptoms: a systematic and critical analysis of 14 double-blind clinical trials in comparison with both standard and novel antipsychotics show consistent findings in favour of clozapine, with all but three of the reports demonstrating superiority. The review of studies allow us to say little about the predictors of treatment response, time to clozapine response and about the impact of clozapine on the quality of patients'life and longer-term outcome. Treatment options for clozapine non-responders are reviewed. 2) Risk of EPS: clozapine is considered to have a minimal risk of EPS and in all studies where a valid methodology was used, a clear superiority over the other neuroleptics is demonstrated. It is pointed out that, if the prevalence and incidence of EPS with clozapine is low, it is not zero. All the studies assessing clozapine treatment for TD have major methodological limitations, so no final conclusion can be drawn. 3) Efficacy for primary and secondary negative symptoms and neurocognitive effects: the data of clinical studies where negative symptoms scales were used favour clozapine in terms of improvement. However most of the studies were carried out in populations with predominantly positive symptoms. With regard to the need to distinguish primary and secondary symptoms, data are conflicting regarding the benefit of clozapine. Due to the lack of studies with a valid methodology, no definitive conclusion can be drawn about the efficacy on clozapine on the deficit syndrome and on neurocognitive disorders. 4) Impact on suicide risk: 4 out of 6 retrospective studies provide evidence for the ability of clozapine therapy to reduce suicidal behaviour. The results of a recent randomized, parallel-group study designed to compare clozapine versus olanzapine in preventing suicide attempts seems to confirm this hypothesis. We also address the tolerability and safety data, especially haematologic, comitial, cardiovascular and metabolic side-effects. The effectiveness of blood monitoring for the management of neutropenia and agranulocytosis demands that the recommendations are strictly followed. The use of clozapine at doses higher than 600 mg daily should follow published recommendations, in order to minimize the risk of seizures; these include anticonvulsant regimens based on blood levels. With regard to the cardiovascular mortality, if clozapine therapy has negligible effects on QT interval, its association with potential fatal myocarditis cannot be excluded in young patients who should be investigated if they develop cardiac symptoms in the first weeks of treatment. Available data support the notion that the frequency of bodyweight gain is high with several new antipsychotics, including clozapine. Potential long term effects of bodyweight gain on mortality and morbidity have to be taken into consideration. The pharmacological mechanisms underlying the "unique clozapine profile" is discussed. Clozapine remains the only antipsychotic with efficacy at relatively low D2 receptor occupancy. The pharmacogenetic and pharmacokinetic aspects are also reviewed. Finally, the place of clozapine in the current treatment of schizophrenia is highlighted to inform the development of guidelines for clinical management.
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PMID:[Leponex, 10 years after -- a clinical review]. 1562 52

Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.
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PMID:Treatment of behavioural symptoms and dementia in Parkinson's disease. 1581 Aug 93

Cognitive decline and dementia affect approximately 30% to 40% of patients with idiopathic Parkinson's disease during the course of their illness. PD-dementia (PDD) and dementia with Lewy bodies (DLB) are second to Alzheimer's disease in causing degenerative dementia in the elderly. The nosological distinction of the conditions has remained controversial because of broad clinical and pathological overlap. Treatment issues in both clinical settings are virtually identical. Treatment of Parkinsonism is often complicated by drug-induced psychosis and reduced levodopa responsiveness. Cognition, alertness, attention, as well as apathy or aggressive behavior have been shown to respond to treatment with cholinesterase inhibitors in randomized controlled trials both in DLB and PDD. Such treatment may also improve hallucinosis, but many patients will require add-on treatment with atypical neuroleptics to control drug-induced psychotic reactions. Clozapine and quetiapine are the drugs most commonly used and, contrary to classic neuroleptics, risperidone or olanzapine do not seem to cause severe side effects according to published data.
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PMID:Treatment of dementia with Lewy bodies and Parkinson's disease dementia. 1609 95

Clozapine is efficacious for treating dopaminergic psychosis in Parkinson's disease and ameliorates l-DOPA-induced motor complications. Based on its pharmacology and reported enhancing effects on dopamine metabolism and tyrosine hydroxylase activity, we investigated whether it could modulate the activity of aromatic l-amino acid decarboxylase (AAAD), the second enzyme for the biosynthesis of catecholamines and indoleamines. A single dose of clozapine increased AAAD activity of striatum in a dose- and time-dependent manner. At 1 h, enhanced enzyme activity was characterized by an increased V(max) for substrate and cofactor and was accompanied by elevated levels of protein in striatum and mRNA in substantia nigra, ventral tegmental area, locus coeruleus, and raphe nuclei. Acute clozapine increased tyrosine hydroxylase activity in striatum but with differing temporal patterns from AAAD and heightened dopamine metabolism. Interestingly, the response of the dopaminergic markers to clozapine was greater following a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion. Chronically administered clozapine increased AAAD activity and protein and dopamine metabolism in striatum without affecting tyrosine hydroxylase. Exogenous l-DOPA decarboxylation was accelerated in the striatum of intact and MPTP-lesioned mice following acute clozapine, and the effect was exaggerated in the MPTP mice. To identify receptors involved, antagonists of receptors occupied by clozapine were employed. D4, 5-HT1(A), and 5-HT2(A), in addition to D1, D2, and D3, antagonists, augmented AAAD activity in striatum, whereas 5-HT2(C), 5-HT3, muscarinic, and alpha-1 and alpha-2 adrenergic antagonists were ineffective. For the first time, these studies provide evidence that clozapine modulates AAAD activity in the brain and suggests that dopamine and serotonin receptors are involved.
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PMID:Clozapine modulates aromatic L-amino acid decarboxylase activity in mouse striatum. 1641 89

Patients with Parkinson's disease (PD) frequently complain of sleep problems. These can be due to several factors, and the approach to their management depends on careful consideration of the various possible factors in each case. 1. Older people, in general, require less sleep. After retirement, people may also engage in less physical activity, and this factor is of course even more pronounced in patients with PD because of their illness. 2. Daytime naps, either spontaneous or due to drugs, reduce the need for nocturnal sleep. Explanation of these physiological and circumstantial changes may help those PD patients who manifest these consequences. 3. The existence of a severe progressive disease as well as social isolation have psychologic consequences, such as anxiety and depression, that may manifest as insomnia. Furthermore, depression is part of the disease, frequently antedating the motor manifestations, and may manifest as insomnia. 4. In advanced disease, patients may be immobile and have difficulty in getting up or even turning in bed. This causes great inconvenience, and may impair sleep. Long acting anti-Parkinson drugs such as cabergoline or rotigotine patch may help. 5. In some cases, unpleasant hallucinations may appear which prevent the patient from falling asleep. These may respond to atypical neuroleptics. Clozapine and quetiapine are particularly useful, but require attention to possible adverse effects.
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PMID:Management of sleep problems in Parkinson's disease. 1704 98

Clozapine has been used as an attempt to manage levodopa complications in advanced Parkinson's disease (PD). To investigate the use of clozapine in this context in a Brazilian sample, a retrospective chart review was carried out at the Movement Disorders Clinic from the Federal University of Minas Gerais. This study enrolled 43 PD patients who used or were in use of clozapine. Patients had a mean age of 64 years and a mean UPDRS score of 55. Clozapine was indicated for dyskinesias in 17 patients, for psychosis in 15 and for both reasons in 11. The average maximum dose was 70 mg/day. Twenty six patients used it for a mean of 3.5 years. Twenty nine presented an improvement of their condition, 9 remained clinically stable. Twenty subjects interrupted the use of clozapine, being 9 due to adverse effects. Clozapine may play a role in the management of motor and psychiatric complications in PD, but it is associated with low tolerability.
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PMID:Use of clozapine in Brazilian patients with Parkinson's disease. 1894 49


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