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)

We completed a single site, double-blind, placebo-controlled, parallel design study of quetiapine for hallucinations in PD. Thirty-one subjects with PD and prominent visual hallucinations and Mini-Mental State Examination score >21 were randomly assigned in a 2:1 drug to placebo ratio, up to 200 mg daily of quetiapine or matching placebo given in two doses. They were seen at 3 weeks (100 mg/day) and 12 weeks (200 mg/day, with optional dose reduction). Evaluation included the Unified Parkinson's Disease Rating Scale (UPDRS), the Baylor PD Hallucination Questionnaire, and a battery of neuropsychological tests. The demographics between subjects randomized to drug (n = 21) vs. placebo (n = 10) were similar. The final dose of active drug was 200 (n = 11), 150 (n = 2), 100 (n = 3), and 75 (n = 1) mg per day. All placebo subjects were on the equivalent of 200 mg per day. The UPDRS Activities of Daily Living and Motor scores did not significantly change compared to placebo. Compared to placebo, there were no significant changes in our hallucination questionnaire, the Brief Psychiatric Rating Scale (BPRS), or question 12 (hallucination item) of the BPRS. There were no significant changes on any of the neuropsychological measures. Adverse events on drug included sedation (n = 9), but no drug-related adverse events precipitated discontinuation and none were rated as serious. Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo. Larger doses of drug and greater sample sizes might be considered in future studies.
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PMID:Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease. 1580 Sep 37

We investigated the usefulness of quetiapine and olanzapine for delusion in nine patients with Parkinson's disease (PD). Two of five patients initially treated with quetiapine showed resolution of delusion on low dose (25 mg and 50 mg/day), whereas three patients had no improvement in spite of increasing the dose to 300 mg/day. Quetiapine non-responders had a tendency to more severe delusion and dementia compared with responders. Not only all four patients initially treated but also two of three quetiapine non-responders showed a remarkable resolution of delusion on olanzapine. In particular, three of seven patients responded to an extremely low dose of 0.625 mg/day. However, severe motor debilitation was observed in one patient treated with 1.25 mg/day. Olanzapine might be useful for delusion of PD in patients not responded to quetiapine, although it should be started at a very low dosage to ameliorate worsening parkinsonism.
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PMID:[The efficacy of olanzapine for delusion in patients with Parkinson's disease]. 1602 44

Quetiapine is an atypical antipsychotic with sedative properties frequently used to treat hallucinations and psychosis in Parkinson disease (PD). The objective of this trial is to evaluate quetiapine for insomnia in nonpsychotic PD patients. Fourteen consecutive PD patients with frequent insomnia and without psychotic symptoms were treated openly for 12 weeks with a single evening dose of quetiapine. The dose was adjusted according to clinical improvement and tolerance. The severity of insomnia was assessed using the Pittsburgh Sleep Quality Index (PSQI), daytime sleepiness was evaluated with the Epworth Sleep Scale (ESS), and motor performance was evaluated using the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). All evaluations were done before and 1, 2, and 3 months after initiation of treatment. Total PSQI basal scores were 13.6 +/- 3.7 points. The PSQI score improved in 11 patients and was reduced by 3.8 +/- 3.9 points by the end of the study (P < 0.01). The ESS score was reduced by 4.3 +/- 3.7 points (P < 0.01). The mean quetiapine dose was 31.9 mg/day. No significant change was observed in the motor scale. Two patients were discontinued due to nonserious adverse effects. These results suggest that quetiapine may be a safe and effective treatment of insomnia in PD patients. Double-blind studies will probably confirm these findings.
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PMID:Quetiapine for insomnia in Parkinson disease: results from an open-label trial. 1606 98

Polysomnographic studies of Parkinson's disease (PD) patients with visual hallucinations (VH) usually reveal short, fragmented rapid eye movement (REM) sleep, with lower sleep efficiency and reduced total REM sleep. Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD. To confirm quetiapine's efficacy in improving VH, and to determine whether the mechanism was due to its effect on REM sleep architecture, we performed a pilot, double-blind, placebo-controlled study. Sixteen PD patients experiencing VH were recruited. Eight patients were randomized to quetiapine and eight patients to placebo. Patients underwent pre- and post-treatment polysomnography. The Clinical Global Impression Scale (CGIS), Brief Psychiatric Rating Scale (BPRS), and Unified Parkinson Disease Rating Scale (UPDRS) motor subscale were obtained. There were no differences in baseline characteristics between the treatment arms except that the placebo group had more sleep in stage REM (74.7 min vs. 40.1 min; p < .001). Data were imputed for all patients who prematurely discontinued (four quetiapine and one placebo) in an intention-to-treat analysis. The average quetiapine dose was 58.3 mg/day. While there was no significant difference in the change in REM duration pre- vs. post-treatment in either arm, patients randomized to quetiapine improved on the CGIS (p = .03) and the hallucination item of the BPRS (p = .02). No difference was noted in the UPDRS motor scores. Despite the small sample, this is the first double-blind trial to show quetiapine's efficacy over placebo in controlling VH in the PD population. However, normalization of sleep architecture was not supported as the mechanism.
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PMID:Quetiapine improves visual hallucinations in Parkinson disease but not through normalization of sleep architecture: results from a double-blind clinical-polysomnography study. 1991 48

Patients with Parkinson's disease (PD) have a high risk of psychiatric complications, like depressive or psychotic syndromes, dementia and sleep disorders. Although these disorders may even precede the onset of motor symptoms, they are often not recognized and therefore not adequately treated. This article provides a comprehensive overview of the therapeutic options of the most commonly observed psychopathological syndromes in PD. In the case of depressive syndromes medication could be optimized by making use of dopamine agonists that have been proven to have antidepressant properties. In recent studies tricyclic antidepressants showed stronger effects than SSRI. Psychotic symptoms are most often evoked by dopaminergic therapy or are seen in the course of cognitive decline. The therapeutic regimen should be built mainly on L-Dopa medication in the lowest tolerated dose, if required in combinations with COMT-Inhibitors. When antipsychotic medication is indicated, clozapine is the first choice. Quetiapine might also be useful in many patients. Psychotic symptoms in demented patients may respond to cholinesterase-inhibitors, that also delay cognitive decline. Patients with PD require an individually optimized therapeutic regimen not only for motor symptoms, but also for frequently occurring psychiatric syndromes since these strongly influence the patients' and their caregivers' quality of life, are predictors for hospitalization and therefore have great economic importance for health care systems.
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PMID:[Treatment of mental disorders in patients with Parkinson's disease]. 2042 92

Psychotic symptoms are common in Parkinson's disease (PD), generally associated with the medications used to treat the motor symptoms. On rare occasion they occur in patients not taking medication for PD. Psychotic symptoms are usually hallucinations, typically visual, less commonly auditory, and rarely in other domains. Hallucinations are generally stereotyped and without emotional content. Initially patients usually have insight so that the hallucinations are benign in terms of their immediate impact but have poor prognostic implications, with increased risk of dementia, worsened psychotic symptoms and mortality. Delusions occur in about 5-10% of drug treated patients and are considerably more disruptive, being paranoid in nature, often of spousal infidelity or abandonment by family. Treatment of Parkinson's disease psychosis (PDP) focuses on reducing the psychiatric symptom load while balancing the competing problem of mobility. Contributors to the psychotic symptoms should be searched for, such as systemic illness and other psycho-active medications. If none are identified or can be eliminated then the PD medications should be reduced to the lowest levels that allow tolerable motor function. Once this level has been reached there are two schools of thought on treatment, using either acetylcholinesterase inhibitors or atypical anti-psychotics. Only clozapine has level I evidence to support its use. Quetiapine is the only other anti-psychotic free of motor side effects, but it has failed double blind placebo controlled trials to demonstrate efficacy.
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PMID:Parkinson's disease psychosis 2010: a review article. 2053

Parkinson's disease (PD) patients often develop psychotic symptoms that severely affect quality of life and limit the use of medications to ameliorate motor symptoms. Psychotic symptoms are a major cause for nursing home placement. While these symptoms do not always require treatment, they often do but antipsychotic drugs all share the common pharmacological mechanism of blocking dopamine D2 receptors which may worsen motor problems in this very vulnerable population. Double blind, placebo controlled trials (DBPCT) have shown that clozapine is effective at controlling the psychotic symptoms at doses far below those used in schizophrenia, without worsening motor function, even improving tremor. DBPCT have demonstrated that olanzapine worsens motor function without improving psychosis. Quetiapine has been shown in DBPCT to be free of motor side effects in PD patients but not effective, whereas many open label studies have indicated that quetiapine is effective. The other atypical have been the subjects of conflicting open label reports. The effects of the atypicals in PD psychosis is reviewed.
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PMID:Atypical antipsychotic drugs in the treatment of Parkinson's disease. 2209 76

Cognitive impairment and dementia pose particular challenges in the management of patients with Parkinson's disease (PD). Decision-making capacity can render patients vulnerable in a way that requires careful ethical considerations by clinicians with respect to medical decision making, research participation, and public safety. Clinicians should discuss how future decisions will be made as early in the disease course as possible. Because of cognitive, visual, and motor impairments, PD may be associated with unsafe driving, leading to early driving cessation in many. DBS of the STN and, to a lesser degree, globus pallidus interna (GPi) has consistently been associated with decreased verbal fluency, but significant global cognitive decline is usually not observed in patients who undergo rigorous selection. There are some observations suggesting lesser cognitive decline in GPi DBS than STN DBS, but further research is required. Management of PD dementia (PDD) patients involves both pharmacological and nonpharmacological measures. Patients with PDD should be offered treatment with a cholinesterase inhibitor taking into account expected benefits and potential risks. Treatment with neuroleptics may be necessary to treat psychosis; classical neuroleptics, as well as risperidone and olanzapine, should be avoided. Quetiapine might be considered first-line treatment because it does not need special monitoring, although the strongest evidence for efficacy exists for clozapine. Evidence from randomized, controlled studies in the PDD population is lacking; selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors may be used to treat depressive features. Clonazepam or melatonin may be useful in the treatment of rapid eye movement behavior disorder.
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PMID:Cognitive impairment and dementia in Parkinson's disease: practical issues and management. 2475 14

Deep Brain Stimulation represents a therapeutic option for PD patients. In this paper, we present and discuss a case of acute delirium and psychosis manifesting after DBS in a 58-years-old man affected by Parkinson's Disease. We highlight the importance of an exhaustive psychiatric evaluation in candidates for DBS and we underline the severity and non-reversibility of some adverse events associated with the implantation, suggesting the use of Quetiapine in the management of these effects. Acute psychosis may be listed as a potential severe adverse event associated with DBS, even in patients without a clear cut previous history of psychiatric disorders.
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PMID:A Long Term Effects of a New Onset Psychosis after DBS Treated with Quetiapine in a Patient with Parkinson's Disease. 2567 Sep 58

Acute psychosis developed in an elderly patient with Parkinson disease and she was admitted and treated with quetiapine (Seroquel). One day later, high fever unexplained by infection appeared associated with restlessness, confusion, convulsion, leukocytosis, and extreme serum creatine kinase levels. She died of neuroleptic malignant syndrome (NMS) despite intensive treatment. Quetiapine is an atypical neuroleptic agent, rarely associated with NMS in the absence of other contributing drugs. Our case strongly establishes quetiapine-induced NMS (Naranjo scale 6) and is also unique in the abrupt onset and severe refractory course. The steep increase in the prescription of quetiapine worldwide mandates better recognition of this severe adverse reaction, which is fortunately rare, to allow immediate drug withdrawal and appropriate treatment.
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PMID:Fatal Neuroleptic Malignant Syndrome Associated With Quetiapine. 2613 4


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