quetiapine-fumarate and Lewy-Body-Disease

We performed a systematic review of randomized controlled trials to assess the high-level evidence regarding the role of quetiapine in the treatment of psychosis in patients with neurodegenerative parkinsonian disorders. Studies were included in the qualitative review if they (1) enrolled participants with diagnosis of Parkinson disease, Lewy body dementia, or any other neurodegenerative parkinsonian disorders; (2) assessed the efficacy of quetiapine; and (3) evaluated psychotic and motor outcomes using validated tools. Of the 341 manuscripts identified, 7 studies fulfilled our inclusion criteria. The studies' risk of bias was considered low. A total of 241 participants enrolled in these trials. Heterogeneity was high due to inclusion criteria, user definitions, assessment tools, and study design. Although not causing any motor deterioration, quetiapine failed to significantly reduce psychotic symptoms compared to placebo when objectively assessed on the Brief Psychotic Rating Scale, the most frequently reported scale in these studies. High loss to follow-up and dropout rates as well as significant improvement in psychotic symptoms in the placebo groups may have affected measurements of possible positive medication effects.

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Lewy Body Disease; Male; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Aripiprazole; Cholinesterase Inhibitors; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Humans; Lewy Body Disease; Male; Parkinson Disease; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones

Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a neurodegenerative disorder now considered to be the second most common cause of dementia after Alzheimer's disease. Postmortem findings suggest that DLB accounts for 20% to 34% of all dementia cases and is often underdiagnosed. Salient features of DLB include fluctuations in cognition, perceptual abnormalities (e.g., visual hallucinations), and mild parkinsonism. Other symptoms include frequent falls, nighttime agitation, and depression. DLB symptomatology can be partly explained by the extensive destruction of dopaminergic and acetylcholinergic pathways caused by neurodegeneration. For this reason, DLB patients are especially vulnerable to the antidopaminergic and anticholinergic actions of most conventional antipsychotics, which makes treatment of the psychotic symptoms of DLB extremely difficult. Patients are particularly sensitive to developing extrapyramidal symptoms (EPS) and also to the potentially fatal complication of neuroleptic sensitivity, which affects approximately 50% of DLB patients. Therefore, a need exists for antipsychotic drugs with less propensity to induce EPS and reduced affinity for dopamine and acetylcholine receptors. Here we review studies evaluating the efficacy and tolerability of atypical antipsychotics for the treatment of psychoses associated with DLB. Olanzapine appears to be poorly tolerated, and risperidone has been associated with high risk of neuroleptic malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations of DLB without causing neuroleptic sensitivity or increasing EPS. Hence, quetiapine is an attractive candidate for the treatment of psychoses in DLB and other dementias.

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Drug-induced iatrogenic hallucinations and psychosis occur in about 30% of Parkinson's disease (PD) patients and are the single most important precipitant for nursing home placement, which carries a grave prognosis. In addition, parkinsonism is a frequent accompaniment to the more common dementing syndromes, Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies (DLB). The five most recent antipsychotic drugs approved by the Food and Drug Administration in the United States have been marketed as "atypical" antipsychotics (AA) due to their relative freedom from extrapyramidal symptoms when used in schizophrenia patients. The use of these newer antipsychotic drugs in PD and other parkinson-sensitive populations represents the most stringent test to their freedom from motor side effects. To date, clozapine, risperidone, olanzapine, and quetiapine have been studied in parkinson-vulnerable populations. This article reviews the data and highlights the differences that these four drugs have on motor function. It also emphasizes the challenges in evaluating the available data on the motor effects of AA, especially on the non-PD elderly and cognitively impaired population. Suggestions are made for future research to improve the interpretability of these studies.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia, Vascular; Dibenzothiazepines; Hallucinations; Humans; Iatrogenic Disease; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

To assess the efficacy and tolerability of quetiapine for agitation or psychosis in patients with dementia and parkinsonism.. Multicenter randomized, double-blind, placebo-controlled parallel groups clinical trial involving 40 patients with dementia with Lewy bodies (n = 23), Parkinson disease (PD) with dementia (n = 9), or Alzheimer disease with parkinsonian features (n = 8). The main outcome measure for efficacy was change in the Brief Psychiatric Rating Scale (BPRS) from baseline to 10 weeks of therapy. For tolerability it was change in the Unified PD Rating Scale (UPDRS) motor section over the same time period. The trial was confounded by the need for a design change and incomplete recruitment.. No significant differences in the primary or secondary outcome measures of efficacy were observed. An unexpectedly large placebo effect, inadequate dosage (mean 120 mg/day), and inadequate power may have contributed to lack of demonstrable benefit. Quetiapine was generally well-tolerated and did not worsen parkinsonism, but was associated with a trend toward a decline on a measure of daily functioning.. Quetiapine was well-tolerated and did not worsen parkinsonism. Although conclusions about efficacy may be limited, the drug in the dosages used did not show demonstrable benefit for treating agitation or psychosis in patients with dementia and parkinsonism. These findings are in keeping with prior studies reporting limited efficacy of various medications for reducing behavioral problems in demented patients.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antiparkinson Agents; Antipsychotic Agents; Cholinesterase Inhibitors; Confounding Factors, Epidemiologic; Dementia; Dibenzothiazepines; Donepezil; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indans; Lewy Body Disease; Male; Neuropsychological Tests; Parkinson Disease; Patient Selection; Piperidines; Placebo Effect; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Research Design; Severity of Illness Index; Treatment Failure

Most clinicians perceive psychosis in dementia with Lewy bodies (DLB) as more difficult to treat than Parkinson's disease, yet there are no reports comparing the antipsychotic response between the 2 disorders.. All charts of Parkinson's disease and DLB patients at our Movement Disorders Center, Memorial Hospital of Rhode Island, Pawtucket, given quetiapine for psychosis were reviewed. Demographic data, including type and severity of psychosis, before and after Unified Parkinson's Disease Rating Scale (UPDRS)-motor scores, motor worsening, and treatment response (recorded as poor/none, partial, or total), were obtained. The chi-square test was used to assess differences in efficacy and tolerability of quetiapine between Parkinson's disease and DLB patients.. Eighty-seven Parkinson's disease and 11 DLB patients with psychosis were analyzed. No significant difference in mean age, levodopa dose, quetiapine dose, duration of quetiapine use, or baseline UPDRS-motor score was noted between Parkinson's disease and DLB patients. Eighty percent (70/87) of Parkinson's disease patients and 90% (10/11) of DLB patients had partial to complete resolution of psychosis using quetiapine (p = .40). Motor worsening was noted at one point in 32% (28/87) of Parkinson's disease and 27% (3/11) of DLB patients over the duration of quetiapine use (p = .74).. Long-term quetiapine use was generally well tolerated in this geriatric Parkinson's disease and DLB population. Mild motor worsening occurred in some patients. No significant difference in long-term efficacy and motor worsening associated with quetiapine treatment was noted between the 2 disorders.

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Humans; Levodopa; Lewy Body Disease; Parkinson Disease; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Quetiapine Fumarate; Retrospective Studies; Severity of Illness Index; Treatment Outcome

BACKGROUND Antidopaminergic medications, including antipsychotics, are known to worsen motor and neuropsychiatric symptoms, including cognition and psychosis, in patients with dementia with Lewy body (DLB). The intensity of worsened clinical symptoms may vary and can result in mortality in certain situations. There have been some reports supporting clozapine, quetiapine and pimavanserin use in psychosis control in this population. CASE REPORT We describe the case of 75-year-old man with diagnosis of DLB and the post-treatment outcome with olanzapine for psychosis during hospitalization. He experienced worsened cognitive and motor functions. Discontinuation of olanzapine resulted in resolution of the clinical worsening. Further, re-initiation of Pimavanserin helped treat his hallucinations. He returned back to his baseline during a follow-up visit in the clinic at 1 month after discharge. Further, we incorporated the use of Best Practice Alert (BPA) as a part of the electronic health record (EHR) system to help providers identify patients prone to neuroleptic sensitivity and help select appropriate medications to treat psychosis in this patient population. CONCLUSIONS Administration of antipsychotics in patients with parkinsonism, especially DLB, requires close clinical monitoring and judicious use. Awareness of morbidity and mortality associated with such use is of importance, especially during hospitalization. From our experience, we incorporated use of BPA, which can help providers make judicious choices while treating this patient population. Pimavanserin, which is FDA-approved for psychosis in Parkinson's disease, could be a potential safe and effective treatment option in this patient population.

Topics: Aged; Antipsychotic Agents; Clozapine; Humans; Inpatients; Lewy Body Disease; Male; Olanzapine; Quetiapine Fumarate

A 76-year-old man presented with complaints of increased confusion, visual hallucinations and decline in memory. He was admitted to the hospital and started on quetiapine 50 mg daily for symptom management. Shortly after, he was diagnosed with Lewy body dementia and started on rivastigmine, a cholinesterase inhibitor (ChEI), at 1.5 mg two times per day. The patient's symptoms continued to worsen and antipsychotics increased for aggressive behaviour. After he became physically aggressive, an extensive medication management review was conducted, prompting an alternative treatment strategy. The quetiapine dose was reduced from 150 mg daily to 12.5 mg daily, his rivastigmine was increased to 3 mg two times per day and all other antipsychotics were discontinued. The up-titration of his rivastigmine after 10 days of therapy was well tolerated with no adverse effects. He demonstrated a clear clinical response to optimised ChEI therapy and low dose quetiapine, showing improvements in alertness and functioning.

Topics: Aged; Antipsychotic Agents; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Hallucinations; Humans; Lewy Body Disease; Male; Psychotic Disorders; Quetiapine Fumarate; Rivastigmine

Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies.. Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available.. Forty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P = 0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P < 0.01); otherwise, the groups were similar. Time to discontinuation analysis, which accounts for efficacy, safety and tolerability, revealed a lower early pimavanserin discontinuation rate and a higher late pimavanserin discontinuation rate (HR < 1 before day 43, HR > 1 after day 43; P = 0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P = 0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P = 0.001).. Accounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Cohort Studies; Female; Humans; Lewy Body Disease; Male; Middle Aged; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Urea

Topics: Aged; Antipsychotic Agents; Humans; Lewy Body Disease; Male; Neuroleptic Malignant Syndrome; Quetiapine Fumarate

Topics: Aged; Antipsychotic Agents; Humans; Lewy Body Disease; Male; Neuroleptic Malignant Syndrome; Quetiapine Fumarate

A recent large-scale randomized controlled clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study, found a significant worsening of cognitive functioning in a sample of patients with Alzheimer's disease. To date there have been no equally powered studies examining the cognitive effects of atypical antipsychotics in patients with dementia with Lewy bodies, the second most prevalent neurodegenerative disorder. This case report describes a significant cognitive improvement observed through the use of an atypical antipsychotic in a patient with dementia with Lewy bodies. The observed divergence in cognitive responsiveness is discussed mechanistically on both the clinical and neuromolecular level. Limitations to this case study design are presented and discussed. The prudence of caution in importing the results of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study to the dementia with Lewy bodies population is summarized and presented for psychiatrists, neurologists and primary care providers, with an intent to stimulate discussion and further research.

Topics: Antipsychotic Agents; Cognition; Dementia; Dibenzothiazepines; Humans; Lewy Bodies; Lewy Body Disease; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome

We report on the treatment of a patient suffering from dementia with Lewy bodies who initially presented with severe neurological and psychopathological symptoms. After treating the patient with levodopa and clozapine, these symptoms remitted.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Delusions; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Levodopa; Lewy Body Disease; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Severity of Illness Index

Patients with dementia with Lewy bodies (DLB) are particularly vulnerable to adverse effects of neuroleptics; this sensitivity is included among the clinical diagnostic criteria for DLB. Recently atypical neuroleptics, which carry less risk of extrapyramidal side effects than typical agents, have come into increasing use in treating psychotic symptoms and behavioral disturbances related to DLB. The present report is the first to describe a DLB patient who developed neuroleptic malignant syndrome (NMS) induced by quetiapine, an atypical neuroleptic known to have relatively infrequent extrapyramidal side effects in DLB patients. Physicians should be aware of the possibility of the occurrence of NMS in DLB even when atypical neuroleptics are administered.

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Humans; Lewy Body Disease; Male; Neuroleptic Malignant Syndrome; Psychiatric Status Rating Scales; Quetiapine Fumarate

The authors describe here the clinical outcomes of quetiapine treatment in nine patients with dementia with Lewy bodies (DLB) who manifested psychotic symptoms and aggressive behavior. Patients who had a score of 3 or higher on any of the three items of the Neuropsychiatric Inventory (NPI), agitation/aggression, hallucinations, and delusions, were given quetiapine 25-75 mg/day. Each patient's clinical status was assessed at baseline and after 4 and 8 weeks of treatment by using the NPI, Mini-Mental State Examination (MMSE), and Simpson-Angus Scale (S-A). Five of nine patients had a positive response with a decline of more than 50% in the sum of scores for three items of the NPI. The other three patients withdrew from quetiapine treatment due to somnolence or orthostatic hypotension. The remaining patient exhibited no clinically significant change in the NPI score. The S-A scale was not affected by quetiapine treatment in any patient. These findings suggest that quetiapine may be effective in treating psychotic symptoms and disruptive behavior in some patients with DLB. Further placebo-controlled, randomized, double-blind trials with this drug are needed to confirm this observation.

Topics: Aged; Aged, 80 and over; Aggression; Dibenzothiazepines; Humans; Lewy Body Disease; Male; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Donepezil; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Female; Hallucinations; Humans; Indans; Lewy Body Disease; Male; Nootropic Agents; Piperidines; Quetiapine Fumarate