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)

Patients with Parkinson's disease and parkinsonian syndromes (eg, dementia with Lewy body disease, multisystem atrophy, and Shy-Drager syndrome) suffer from daytime sleepiness. This sleepiness is common and very real, often approaching levels observed in the prototypical disorder of sudden-onset sleep, namely narcolepsy/cataplexy. Physicians need to be vigilant in assessing parkinsonian patients for sleepiness because treatment can dramatically enhance quality of life and prevent the significant morbidity and mortality that attends daytime sleepiness. Male patients with advanced disease, cognitive impairment, drug-induced psychosis, and orthostatic hypotension are most at risk for developing pathologic sleepiness. Because primary sleep disorders can coexist with parkinsonism (eg, sleep apnea, insufficient or interrupted sleep), these potential causes should be carefully assessed with polysomnography and treated appropriately. Dopaminomimetics exacerbate sleepiness in a small subset of patients in a dose-dependent fashion. Nonetheless, the primary pathologies involved in parkinsonism appear to be the greatest contributors to daytime sleepiness. Sleepiness in parkinsonism, especially a narcolepsy-like phenotype, may necessitate treatment with wake-promoting agents such as bupropion, modafinil, or traditional psychostimulants.
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PMID:Excessive daytime sleepiness and unintended sleep in Parkinson's disease. 1652 72

Parkinson's disease (PD) patients commonly experience psychotic symptoms, with the most frequent manifestation being visual hallucinations. In PD, psychosis is predominantly drug induced and an important issue for clinicians to address as it increases the risk of nursing home placement as well as mortality. This review summarises the current knowledge regarding the clinical manifestations, pathophysiology and risk factors for drug-induced psychosis in patients with PD and focuses on treatment, especially with regard to the atypical antipsychotics.
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PMID:Combating psychosis in Parkinson's disease patients: the use of antipsychotic drugs. 1654 84

ACADIA Pharmaceuticals is developing ACP-103, lead compound in a series of 5-HT2A inverse agonists, as a potential antipsychotic agent and for the potential treatment of insomnia. Phase II clinical trials in treatment-induced psychosis in Parkinson's disease (PD) patients and in schizophrenic patients are ongoing, as are phase II trials evaluating the effects of the drug on PD symptoms and dyskinesias.
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PMID:ACP-103, a 5-HT2A receptor inverse agonist. 1686 20

"Atypical anti-psychotics" are substances of choice in treating drug-induced psychosis (DP) in Parkinson's disease (PD). We report on four patients with DP who received treatment with ziprasidone after previously applied clozapine and quetiapine had failed. Three patients showed a significant improvement of DP, without deterioration of motor function. In one case, ziprasidone considerably increased decline in off-periods. Two patients developed pathological laughing as a possible side-effect of ziprasidone. Ziprasidone may serve as an additional "atypical anti-psychotic" for the treatment of DP in PD but can also induce deterioration of motor function.
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PMID:Treatment of drug-induced psychosis in Parkinson's disease with ziprasidone can induce severe dose-dependent off-periods and pathological laughing. 1694 33

This double-blind randomized study examined the effect of quetiapine (QTP) on drug-induced psychosis (DIP) in Parkinson's disease (PD). Conventional antipsychotic drugs are associated with adverse extrapyramidal effects. QTP is a new atypical antipsychotic drug used in the treatment of psychosis in PD. A total of 58 consecutive psychotic PD patients (mean age, 75 +/- 8.3 years; mean disease duration, 10.5 +/- 6.4 years; 29 with dementia) were randomly assigned to 2 groups: 30 were treated with QTP (mean dose, 119.2 +/- 56.4 mg) and 28 received placebo for 3 months. The motor part of the Unified Parkinson's Disease Rating Scale, the Brief Psychiatric Rating Scale, the Mini-Mental State Examination, the Hamilton Rating Scale for Depression, the Epworth Sleepiness Score, and the Clinical Global Impression Scale were administered before and during the study. No significant difference was found between the groups in all parameters. There were 32 PD patients (55%) completed the 3-month study (15 [26%] QTP and 17 [29%] placebo). Treatment was interrupted in 15 patients in the QTP and 11 in the placebo groups. This double-blind study did not show a beneficial effect of QTP for the treatment of DIP in PD. The high rate of withdrawal probably influenced the results. Larger double-blind studies are required.
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PMID:Effect of quetiapine in psychotic Parkinson's disease patients: a double-blind labeled study of 3 months' duration. 1703 6

Psychosis due to dopamimetic treatment is a difficult problem in patients with Parkinson's disease (PD). The aim of this structured review with meta-analysis was to evaluate which neuroleptic drugs can efficiently be used to treat drug-induced psychosis (DIP) in Parkinson's disease. Electronic databases were screened for the key words Parkinson's disease and psychosis. Only 7 trials with a satisfactory allocation concealment and data reporting were included into the study. Two trials compared low-dose clozapine versus placebo with a significantly better outcome for clozapine regarding efficacy and motor functioning. In one trial clozapine was compared against quetiapine showing equivalent efficacy and tolerability. However, in two placebo controlled trials quetiapine failed to show efficacy. In two further placebo controlled trials olanzapine did not improve psychotic symptoms and significantly caused more extrapyramidal side effects. Based on randomized trial-derived evidence which is currently available, only clozapine can be fully recommended for the treatment of DIP in PD. Olanzapine should not be used in this indication.
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PMID:Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis. 1707 Jun 75

To investigate whether transcranial brain sonography (TCS) discriminates different courses of idiopathic Parkinson's disease (PD), 101 patients with clinically definite PD were studied. In four patients, TCS was not possible due to insufficient acoustic temporal bone windows. Substantia nigra (SN) hyperechogenicity was found in 96% of assessable patients. Larger SN echogenic size correlated with younger age at PD onset (Spearman correlation, r = -0.383; P < 0.001), but not with age, PD duration, or severity. Marked bilateral SN hyperechogenicity indicated early-onset rather than late-onset PD, and akinetic-rigid (AR) or mixed-type (MX) PD rather than tremor-dominant PD. SN echogenic sizes were larger contralateral to the clinically more affected side in AR PD and MX PD patients. Reduced echogenicity of brainstem raphe was associated with depression (RR = 1.61; 95% CI = 1.05-2.46; P = 0.044) but not with other clinical features. Caudate nucleus hyperechogenicity was, independently from PD duration, related to drug-induced psychosis (RR = 2.40; CI = 1.36-4.22; P = 0.001), but not to motor fluctuations. Lenticular nucleus hyperechogenicity indicated AR PD rather than tremor-dominant PD (RR = 1.44; CI = 1.11-1.86; P = 0.040). Frontal horn dilatation > 15.4 mm (mean of bilateral measurements) indicated increased risk of dementia (RR = 4.11; CI = 1.51-11.2; P = 0.001). We conclude that TCS displays characteristic changes of deep brain structures in different clinical manifestations of PD.
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PMID:Transcranial brain sonography findings in clinical subgroups of idiopathic Parkinson's disease. 1708 96

There was increasing evidence suggesting that angiotensin I-converting enzyme may play an important role in the pathogenesis of PD. Our former study has shown that angiotensin I-converting enzyme gene (ACE) may confer a susceptibility for the risk of Parkinson's disease (PD). Meanwhile, recent studies have emphasized that genetic factors may involve in the occurrence of the adverse effects of chronic L-dopa therapy in PD patients. This study was designed to assess whether genetic polymorphism of the ACE could be a predictor of L-dopa-induced adverse effects in PD. There were 251 patients included in this study and their mean age at onset of disease was 63.3+/-11.4 years. The duration of disease and the treatment with L-dopa was 6.3+/-5.1 and 5.0+/-4.3 years, respectively. The frequency of the homozygote ACE-II genotype of the ACE in PD patients with L-dopa-induced psychosis was significantly higher than that in PD patients without the adverse effect (63.3% vs 43.0%; chi(2)=6.347, OR=1.435, 95%CI=1.105-1.864, p=0.012). However, the ACE polymorphism was not associated with the risk to develop dyskinesia or motor fluctuation induced by L-dopa. Furthermore, a logistic regression analysis confirmed that the ACE-II genotype was an independent risk factor for L-dopa-induced psychosis in PD patients (OR=2.542, p=0.012). In conclusion, results of the study showed that ACE-II genotype might confer a primary predictor for the occurrence of psychosis in L-dopa-treated PD.
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PMID:Genetic polymorphism of the angiotensin converting enzyme and L-dopa-induced adverse effects in Parkinson's disease. 1719 21

There are no standardized diagnostic criteria for psychosis associated with Parkinson's disease (PDPsy). As part of an NIH sponsored workshop, we reviewed the existing literature on PDPsy to provide criteria that distinguish PDPsy from other causes of psychosis. Based on these data, we propose provisional criteria for PDPsy in the style of the Diagnostic and Statistical Manual of Mental Disorders IV-TR. PDPsy has a well-characterized temporal and clinical profile of hallucinations and delusions, which is different than the pattern seen in other psychotic disorders such as substance induced psychosis or schizophrenia. PDPsy is associated with a poor prognosis of chronic psychosis, nursing home placement, and death. Medications used to treat Parkinson's disease (PD) contribute to PDPsy but may not be sufficient or necessary contributors to PDPsy. PDPsy is associated with Lewy bodies pathology, imbalances of monoaminergic neurotransmitters, and visuospatial processing deficits. These findings suggest that PDPsy may result from progression of the disease process underlying PD, rather than a comorbid psychiatric disorder or drug intoxication. PDPsy is not adequately described by existing criteria for psychotic disorders. We established provisional diagnostic criteria that define a constellation of clinical features not shared by other psychotic syndromes. The criteria are inclusive and contain descriptions of the full range of characteristic symptoms, chronology of onset, duration of symptoms, exclusionary diagnoses, and associated features such as dementia. These criteria require validation and may be refined, but form a starting point for studies of the epidemiology and pathophysiology of PDPsy, and are a potential indication for therapy development.
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PMID:Diagnostic criteria for psychosis in Parkinson's disease: report of an NINDS, NIMH work group. 1726 92

Although there is a relatively high prevalence of both idiopathic Parkinson's disease (PD) and epilepsy in the elderly population, and PD occurs more frequently in people with epilepsy, there are no studies investigating the efficacy and tolerability of antiepileptic drugs (AEDs) in people with PD. We describe the case of a 71-year-old man with PD who experienced several seizures. The initiation of antiepileptic treatment with oxcarbazepine (OXC) provoked a severe, long-lasting psychotic state. The patient had previously experienced similar psychotic episodes during dopamine agonist therapy. Because recent animal studies have proven that OXC and its active metabolite exert important dopamine- and serotonin-promoting effects in the limbic area, we assumed that in our case the OXC-induced psychosis was mediated by the dopaminergic system. We concluded that OXC should be used with care in cases of a constellation of PD and epilepsy because of its possible psychiatric side effects. The dopaminergic effect of OXC and its active metabolite might also play an ambivalent, but important role in the treatment of alcohol addiction and bipolar disorder; therefore, further studies are required to investigate its psychopharmacological aspects.
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PMID:Oxcarbazepine may induce psychotic symptoms in Parkinson's disease. 1822 10


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