quetiapine-fumarate and Parkinson-Disease

The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood.. To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP.. We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. We estimated relative standardized mean differences (SMDs) for continuous outcomes and odds ratios (OR) for binary outcomes, with their respective 95% confidence intervals (CIs).. We included 19 unique studies evaluating AAPs in a total of 1,242 persons with PDP. Based on Clinical Global Impression Scale for Severity, pimavanserin (SMD, -4.81; 95% CI, -5.39, -4.24) and clozapine (SMD, -4.25; 95% CI, -5.24, -3.26) significantly improved symptoms compared with placebo. Also, compared to placebo, pimavanserin (OR, 1.16; 95% CI, 1.07, 1.24) significantly improved psychotic symptoms based on Scale for Assessment of Positive Symptoms for Parkinson's Disease Psychosis/Hallucinations and Delusions scores. In comparison to placebo, clozapine (SMD, -0.69; 95% CI, -1.35, -0.02), pimavanserin (SMD, -0.01; 95% CI, -0.56, 0.53), and quetiapine (SMD, 0.00; 95% CI, -0.68, 0.69) did not impair motor function per Unified Parkinson's Disease Rating scale. Based on Mini-Mental State Examination scale, quetiapine (SMD, 0.60; 95% CI, 0.07, 1.14) significantly impaired cognition compared to placebo.. In patients with PDP, pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. With quetiapine being associated with a significant decline in cognition and despite not impairing motor function, our findings suggest that it should be avoided in patients with PDP and reduced cognitive abilities.

Topics: Antipsychotic Agents; Clozapine; Humans; Network Meta-Analysis; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Psychosis is a common problem for people treated for Parkinson's disease. The syndrome is quite stereotypic, with hallucinations being the most common, followed by delusions. While the hallucinations are usually not very bothersome, the delusions are typically paranoid in nature. Treatment is often, but not always, required.. This article reviews the therapeutic approaches of this syndrome focusing on drug treatments used once contributory factors have been removed. This includes a review of the evidence supporting the use of clozapine and, most recently, pimavanserin, the first drug with antipsychotic efficacy that has no effect on dopamine. Treatment with second generation antipsychotic drugs and cholinesterase inhibitors are also reviewed.. Clozapine and pimavanserin have proven efficacy for Parkinson's disease psychosis (PDP), without impairing motor function. In clozapine's favor are its antipsychotic benefits seen within 1 week and its effectiveness in improving tremor in PD. However, this is counterbalanced by the need for blood monitoring, despite the extremely low doses used, and sedation. Pimanvanserin is well tolerated, without sedation or other significant side effects. Its onset of benefit, however takes 4-6 weeks. While quetiapine is also frequently used, its efficacy is not supported by double blinded, randomized trials.

Topics: Antipsychotic Agents; Clozapine; Dopamine; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea

To summarize and evaluate the existing literature regarding medications to treat Parkinson's disease (PD) psychosis.. MEDLINE (1946 to March 2017), EMBASE (1980 to March 2017), CINAHL (1982 to March 2017), and PsychInfo (1887 to March 2017) were searched using the following terms: Parkinson disease, Parkinson's disease, psychotic disorders, psychosis, delusions, and hallucinations.. The search was limited to randomized controlled trials (RCTs) reporting human outcomes. Data extracted included the following: study design, population, setting, intervention, control, outcomes related to psychosis and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool.. After assessment, 16 of 235 studies were included; 11 articles reported comparisons between active drug and placebo, whereas 5 compared clozapine and an active comparator. Placebo-controlled trials demonstrated benefit for clozapine (n = 2) and pimavanserin (n = 2), with no firm benefits observed for quetiapine (n = 4) or olanzapine (n = 3). Comparative studies demonstrated improved efficacy in symptom scores when clozapine or comparator agent (n = 2, quetiapine; n = 1, olanzapine; n = 1, risperidone; and n = 1, ziprasidone) was assessed alone. However, no comparator data suggest that one agent is better than another, and none are yet available for pimavanserin. Overall risk of bias across all studies was moderate to high.. Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Piperazines; Piperidines; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; Urea

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

Psychosis in Parkinson's disease (PD) is one of the greatest determinants of nursing home placement and caregiver stress. Traditionally associated with medications with dopaminergic effect, it has now been linked to other medications and other stressors e.g. systemic illnesses. The development of hallucinations in a PD patient can herald the onset of dementia and usually predicts increased mortality risk. Medication reduction in PD psychosis usually reduces the symptoms; however, this comes at the cost of worsening motor function. If gradually decreasing the patient's medications does not resolve the psychosis, the treatment of choice is an atypical antipychotic. Though only clozapine has level A recommendation for this indication, other atypicals like quetiapine continue to get used for this purpose on account of the logistics involved with clozapine use. Cholinesterase inhibitors are also increasingly being used for PD psychosis on account of the association with dementia. The treatment of PD psychosis is an unmet need in PD management and search for suitable agents constitutes an active area of research in PD.

Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT

Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Humans; Molecular Targeted Therapy; Neurotransmitter Agents; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea

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.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Antipsychotic Agents; Benzodiazepines; Benzothiazoles; Brain; Clonazepam; Desipramine; Dibenzothiazepines; Dopamine Agonists; Humans; Lithium Carbonate; Maprotiline; Melatonin; Neurodegenerative Diseases; Neuroprotective Agents; Olanzapine; Parkinson Disease; Pramipexole; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Valproic Acid

Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack of agreement on the diagnosis of psychosis in PD, poor completion rates, mixed populations that included dementia, and other issues. Several reviews, guidelines, and consensus statements have sought to establish standards for treating these symptoms of PD. In 2006, the American Academy of Neurology (AAN) published a practice guideline (based on articles published up to 2004) for management of depression, psychosis, and dementia in patients with PD. Since then, a number of relevant studies have been published.. The purpose of this article was to review data that have appeared in the literature since publication of the AAN guideline regarding the management of hallucinations and psychosis in PD.. A literature search of the PubMed, CINAHL, and PsychInfo databases was conducted for human studies published in English from January 2004 to June 2010. All clinical studies were included except case reports and case series. Studies with <20 participants were also excluded. Search terms included psychosis, hallucinosis, hallucination, delusion, Parkinson, atypical antipsychotic, neuroleptic, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone.. Thirteen studies were included in the review: 3 studies of clozapine, 7 studies of quetiapine, 2 head-to-head trials comparing quetiapine and clozapine, and 1 noncomparative trial of clozapine or quetiapine interventions. Most of the studies included participants with a mean age in the early to mid 70s and a mean duration of PD typically >10 years.. Results of the identified studies suggested that patients with PD might benefit from long-term clozapine therapy. Results of the quetiapine studies were conflicting. However, no statistically significant difference in effectiveness was found between quetiapine and clozapine in comparative trials. The significance of the differences in treatment responses between patients with dementia and those without dementia remains unclear, and it was not possible to draw conclusions for or against other atypical antipsychotics because of insufficient evidence. Further studies are needed to address the methodologic issues in the current trials and to assess safety issues in larger cohorts.

Topics: Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Comorbidity; Delusions; Dementia; Depression; Dibenzothiazepines; Disease Progression; Guidelines as Topic; Hallucinations; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report; Risperidone

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.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Data Interpretation, Statistical; Dibenzothiazepines; Dopamine; Dopamine Agents; Humans; Olanzapine; Parkinson Disease; Psychotic Disorders; Quality Assurance, Health Care; 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

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; 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

Behavioral problems associated with psychosis in the elderly have a significant negative impact on patients' quality of life and can lead to placement in a nursing home. Because of their decreased propensity to produce extrapyramidal symptoms, atypical antipsychotics such as quetiapine hold promise in the treatment of these vulnerable patients. Quetiapine may, in theory, be particularly advantageous in this regard because of its lack of anticholinergic activity and its relatively loose binding to dopamine receptors. This article reviews the somewhat limited number of clinical studies of the use of quetiapine in treating older patients with schizophrenia and other psychotic disorders, patients with psychosis associated with Alzheimer's disease or dementia with Lewy bodies, and patients with Parkinson's disease and drug-induced psychosis.

Topics: Age Factors; Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dementia; Dibenzothiazepines; Double-Blind Method; Humans; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Treatment Outcome

Psychotic symptoms have become increasingly common in patients with idiopathic Parkinson's disease and other parkinsonian syndromes. This increased prevalence of psychoses is in part a reflection of the greater longevity of people with Parkinson's disease and, to a certain extent, is a consequence of our success in treating the motor symptoms of these syndromes. The psychotic symptoms associated with Parkinson's disease can be as varied as the motor symptoms. They stem from interactions between the underlying neuropathologies of the syndromes and the adverse effects associated with chronic antiparkinsonian drug administration. In patients with advanced Parkinson's disease, there is also a high prevalence of affective comorbidity. This increase in affective symptoms and the relatively high incidence of cognitive and affective side effects of the antiparkinsonian medications contribute to the increase in psychoses observed in these older patients. The most significant risk factors for developing psychosis in Parkinson's disease are (1) coexistence of dementia, (2) protracted sleep disturbances, and (3) nighttime use of long-acting dopaminomimetics. This article reviews the phenomenology, pathophysiology, and treatment of psychosis associated with parkinsonism and discusses how atypical antipsychotic medications have revolutionized the management of the symptoms and improved the quality of life of those affected.

Topics: Algorithms; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Comorbidity; Decision Trees; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Pirenzepine; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate

Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. The use of anti-PD medications has been the most widely identified risk factor for PD psychosis (PDP). However, the pathophysiology of PDP remains unclear. Although the efficacy of electroconvulsive therapy (ECT) for PD had been pointed out, only one study has demonstrated the effectiveness of ECT on both psychotic symptoms and motor symptoms. The aim of this study was to examine the acute effectiveness of ECT on PD and to identify the brain areas associated with PDP.. The study was conducted at Juntendo University Hospital in Tokyo. Eight patients with L-DOPA- or dopamine (DA) agonist-induced PDP, who were resistant to quetiapine treatment, were enrolled. Severity of PD was evaluated using the Hoehn and Yahr stage. Psychotic symptoms were evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS). Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc ECD SPECT) was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. A voxel-by-voxel group analysis was performed using Statistical Parametric Mapping (SPM5).. Our study clearly demonstrated that PDP was significantly less severe after ECT than before ECT, as indicated by change in mean SAPS total domain score (t=7.2, P=0.0002). Furthermore, the patients showed significant improvement in Hoehn and Yahr stage after ECT (t=11.7, P<0.0001). A further notable observation was significant increase in rCBF in the right middle frontal gyrus after ECT.. We conclude that a course of ECT produced notable improvements not only in PDP but also in the severity of PD. The findings of change in rCBF suggest implications for dysfunction in the middle frontal region for patients with PDP.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clinical Trials, Phase I as Topic; Dibenzothiazepines; Disease Progression; Electroconvulsive Therapy; Electroencephalography; Female; Humans; Inpatients; Levodopa; Male; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Regional Blood Flow; Risk Factors; Time Factors; Tokyo; Tomography, Emission-Computed, Single-Photon

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.

Topics: Aged; Antipsychotic Agents; Cohort Studies; Dibenzothiazepines; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Parkinson Disease; Pilot Projects; Polysomnography; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Sleep; Sleep, REM; Treatment Outcome; Visual Perception

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.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Outcome Assessment, Health Care; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index

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

We studied the effect of quetiapine in drug induced psychosis (DIP) in Parkinson's disease (PD) patients with dementia (PDDEM) and without dementia (PDNODEM) in a 6-month open study.. Thirty five consecutive PD patients with DIP (19 of them demented [DSMIV criteria]) were examined. Assessment included Mini-Mental State Examination (MMSE), UPDRS (motor part), Brief Psychiatric Rating Scale (BPRS), Clinical Global Improvement Scale (CGIS) and Hamilton test (for depression). Quetiapine was administered in a flexible dose 25-600 mg daily. Out of the 35 patients included in the study, 24 completed treatment with quetiapine (14 demented and 10 without dementia). Treatment was stopped in 11 patients (5 demented).. Intention to treat patient (ITT) analysis did not show a significant quetiapine effect (BPRS), although in about 30% a good outcome was reported by the family (CGIS). Among the patients who completed the study (n = 24), in the PDNODEM group (n = 10) BPRS improved almost significantly (p = 0.06) while in the PDDEM group the BPRS did not change. According to the CGIS, a good improvement was observed in 50% of the PDDEM group (7/14) and 40% of the PDNODEM group (4/10). Motor features of PD patients worsened mildly (p = 0.05) in the PDDEM group.. In this open trial, quetiapine was not beneficial in the ITT group using the BPRS, although families reported improvement in about 30% of patients (CGIS). Among patients who completed the study, quetiapine was more effective in the PDNODEM group. A double blind study with quetiapine is required.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dementia; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate; Treatment Outcome

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.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Female; Hallucinations; Humans; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Placebos; Quetiapine Fumarate; Surveys and Questionnaires; Treatment Outcome

Drug induced dyskinesias remain a challenging problem in the long term management of Parkinson's disease (PD). We have assessed the effect of quetiapine on dyskinesias in a double blind placebo controlled cross over study.. Nine patients with PD were enrolled and received 25 mg of quetiapine or placebo at night for two weeks in prerandomised order, with one week of wash out between treatment periods. Assessments were made using on-off diaries, self assessment of dyskinesias, and L-dopa challenges at baseline and after each treatment period. Videotapes were rated blindly by two raters using modified Abnormal Involuntary Movement Scale and Goetz scores. Patients subsequently went on open label quetiapine at 50 mg/day, for a mean duration of 30 days, and completed the same self assessment forms.. During the double blind phase, no significant change in dyskinesias was found on either 25 mg of quetiapine or placebo. Duration of off states and Unified PD Rating Scale motor scores also remained unchanged. Moderate tiredness and daytime sleepiness occurred in two patients on quetiapine. One patient dropped out early for unrelated reasons. Eight patients completed the open label phase. On 50 mg/day of quetiapine, a slight reduction in dyskinesias occurred on some scales. Reduction in dyskinesia severity on visual analogue scales was by 50.1%. Off time was not significantly increased. This improvement was not strongly reflected in patients' overall impression of treatment effect. Drowsiness and daytime sleep episodes led to discontinuation in four patients, after completion of the study, and two additional patients stopped treatment after the study because of lack of effect.. Our study failed to demonstrate an antidyskinetic effect of low dose (25 mg) quetiapine. The absence of an increase in parkinsonism combined with a possible antidyskinetic effect on higher doses warrants further investigation.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Cross-Over Studies; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate

Twenty-nine elderly patients who failed treatment with clozapine, risperidone, or olanzapine entered this 24-week, single-center, open-label trial to assess the efficacy of quetiapine (12.5-400 mg/day) for psychosis in patients with Parkinson's disease (PD). Psychiatric, motor, and cognitive assessments were administered at baseline and at periodic intervals for 24 weeks. These included the Brief Psychiatric Rating Scale (BPRS), Neuropsychiatric Inventory (NPI), Unified Parkinson's Disease Rating Scale (UPDRS) and tests of intellectual functioning, attention, and memory. Repeated measures statistical analysis was used to assess change from baseline. The results revealed significant improvements in the 24-week BPRS total score and NPI psychosis subscale scores, with no decline in UPDRS total or motor subscale scores. There was also significant improvement in recall scores on cognitive measures. These results indicate that quetiapine may treat psychotic symptoms and improve cognition without worsening motor function in patients with PD, suggesting that quetiapine is an effective and well-tolerated antipsychotic in this population.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Brief Psychiatric Rating Scale; Delusions; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Hallucinations; Humans; Levodopa; Male; Middle Aged; Neurologic Examination; Neuropsychological Tests; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Dopamine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate

This study investigated the efficacy and safety of quetiapine versus clozapine in parkinsonian patients with dopaminergic psychosis. All patients fulfilling the inclusion criteria were randomly assigned to receive either quetiapine or clozapine. The duration of the trial was 12 weeks. The severity of psychosis was assessed using the BPRS and the Clinical Global Impression Scale-Severity subscale (CGI-S). The UPDRS III was used to monitor the progression of PD during the study period. Twenty patients, 10 on clozapine, and 10 on quetiapine, completed the study. The psychopathological state, as assessed by the BPRS and by the CGI-S, improved significantly ( p<0.001) from baseline in both treatment groups. No differences were found between clozapine and quetiapine at each assessment time. The UPDRS score decreased significantly ( p<0.05) in the clozapine group, while was almost unchanged in the quetiapine group.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Disease Progression; Dopamine Agonists; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate

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

Eleven patients with Parkinson's disease (PD) and acute psychosis received flexible doses of quetiapine between 25 and 300 mg/day based on clinical response and tolerance. Ten patients were receiving dopaminergic agents at baseline. Serial efficacy ratings (Brief Psychiatric Rating Scale, Clinical Global Impressions Scale), neuromuscular symptom assessments (Abnormal Involuntary Movement Scale, Simpson-Angus Scale, Unified Parkinson's Disease Rating Scale [UPDRS]), and adverse events monitoring were performed for up to 52 weeks. The patients had moderate hallucinations and/or delusions at baseline before the initiation of quetiapine. Nine of the 11 patients completed at least 12 weeks of treatment. Quetiapine was well tolerated in all but one patient, who became dizzy within the first week and withdrew from the study. Ten patients presented with moderate visual hallucinations. Quetiapine was markedly effective in controlling visual hallucinations in six of these patients. Symptoms of paranoia or delusions were less responsive to quetiapine. Four patients withdrew because of adverse events or comorbid medical problems, two withdrew because of a lack of efficacy, and five completed 52 weeks of treatment. The introduction of quetiapine did not exacerbate parkinsonian symptoms. Motor dysfunction, as measured by the UPDRS, revealed a slow, gradual worsening consistent with the progression of PD. Atypical antipsychotic medications such as quetiapine have a reduced likelihood of causing adverse drug-induced parkinsonism and therefore a possible role in treating psychotic symptoms in patients with PD.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Parkinson Disease; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Quetiapine Fumarate

Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Brief Psychiatric Rating Scale; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate; Severity of Illness Index

Psychoses are a common clinical problem in patients with Parkinson's disease. Treatment with typical neuroleptics or withdrawal of antiparkinsonian drugs may improve mental symptoms but will worsen the parkinsonism. Quetiapine (Seroquel), ICI 204,636, is a novel antipsychotic medication with a low potential for producing extrapyramidal side effects. In this open-label clinical study of 2 patients with Parkinson's disease, treatment with Seroquel successfully controlled psychotic symptoms without worsening of motor disability.

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

Parkinson disease (PD) psychosis (PDP) is a disabling non-motor symptom. Pharmacologic treatment is limited to pimavanserin, quetiapine, and clozapine, which do not worsen parkinsonism. A Food and Drug Administration black box warning exists for antipsychotics, suggesting increased mortality in elderly patients with dementia. However, the reasons for higher mortality are unknown.. Expanding on prior work exploring mortality in treated PDP patients, we conducted a retrospective comparison to understand the links between treatment regimen, clinical characteristics, and negative outcomes.. Electronic medical record data extraction included clinically diagnosed PD patients between 4/29/16-4/29/19 and excluded patients with primary psychiatric diagnoses or atypical parkinsonism. Mortality and clinical characteristics during the study period were compared between untreated patients and those receiving pimavanserin, quetiapine, or both agents (combination). Mortality analyses were adjusted for age, sex, levodopa equivalent daily dose (LEDD), and dementia.. The pimavanserin group (n = 34) had lower mortality than the untreated group (n = 66) (odds ratio = 0.171, 95% confidence interval: 0.025-0.676, p = 0.026). The untreated group had similar mortality compared to the quetiapine (n = 147) and combination (n = 68) groups. All treated groups had a higher LEDD compared to the untreated group, but no other differences in demographics, hospitalizations, medical comorbidities, medications, or laboratory values were found between the untreated and treated groups.. PDP patients receiving pimavanserin had lower mortality than untreated patients. We found no other clear differences in clinical characteristics to explain the mortality risk. Prospective randomized trials are needed to definitively identify the optimal PDP treatment regimen and associated risks.

Topics: Aged; Antipsychotic Agents; Dementia; Humans; Levodopa; Parkinson Disease; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Urea

This study aimed to examine differential prescribing due to channeling and propensity score non-overlap over time in new versus established treatments for common neurological conditions. We conducted cross-sectional analyses on a national sample of US commercially insured adults using 2005-2019 data. We compared new users of recently approved versus established medications for management of diabetic peripheral neuropathy (pregabalin versus gabapentin), Parkinson disease psychosis (pimavanserin versus quetiapine), and epilepsy (brivaracetam versus levetiracetam). Within these drug pairs, we compared demographic, clinical, and healthcare utilization characteristics of recipients of each drug. In addition, we fit yearly propensity score models for each condition and assessed propensity score non-overlap over time. For all three drug pairs, users of the more recently approved medications more frequently had prior treatment (pregabalin = 73.9%, gabapentin = 38.7%; pimavanserin = 41.1%, quetiapine = 14.0%; brivaracetam = 93.4%, levetiracetam = 32.1%). Propensity score non-overlap and its resulting sample loss after trimming were the greatest in the first year that the more recently approved medication was available (diabetic peripheral neuropathy, 12.4% non-overlap; Parkinson disease psychosis, 6.1%; epilepsy, 43.2%) and subsequently improved. Newer neuropsychiatric therapies appear to be channeled to individuals with refractory disease or intolerance to other treatments, leading to potential confounding and biased comparative effectiveness and safety study findings when compared to established treatments. Propensity score non-overlap should be reported in comparative studies that include newer medications. When studies comparing newer and established treatments are critically needed as soon as new treatments enter the market, investigators should recognize the potential for channeling bias and implement methodological approaches like those demonstrated in this study to understand and improve this issue in such studies.

Topics: Adult; Cross-Sectional Studies; Diabetic Neuropathies; Epilepsy; Gabapentin; Humans; Levetiracetam; Parkinson Disease; Pregabalin; Quetiapine Fumarate

The use of antipsychotics in persons with Parkinson's disease (PD) is common, although their use may aggravate the symptoms of PD. Clozapine and quetiapine are the only antipsychotics recommended in PD treatment guidelines. Information on factors associated with initiation of antipsychotics is needed. We investigated whether recent hospitalization is associated with initiation of antipsychotics in persons with PD, and whether discharge diagnoses differ between those who had antipsychotics initiated and those who did not.. Nested case-control study in the nationwide register-based Finnish Study on Parkinson's disease (FINPARK).. The FINPARK study includes 22,189 persons who received an incident, clinically verified PD diagnosed during 1996-2015 and were community-dwelling at the time of diagnosis. The cases were 5088 persons who had antipsychotics initiated after PD diagnosis, identified with 1-year washout. The controls were 5088 age-, sex-, and time from PD diagnosis-matched persons who did not use antipsychotics on the matching date (antipsychotic purchase date). Recent hospitalization was defined as discharge in the 2-week period preceding the matching date.. Associations were investigated with conditional logistic regression.. Quetiapine was the most commonly initiated antipsychotic (72.0% of cases), followed by risperidone (15.0%). Clozapine was initiated rarely (1.1%). Recent hospitalization associated strongly with antipsychotic initiation [61.2% of cases and 14.9% of controls, odds ratio (OR) 9.42, 95% CI 8.33-10.65], and longer hospitalizations were more common among cases. PD was the most common discharge diagnosis category (51.2% of hospitalized cases and 33.0% controls), followed by mental and behavioral disorders (9.3%) and dementia (9.0%) among cases. Antidementia and other psychotropic medication use were more common among cases.. These results suggest that antipsychotics were initiated because of neuropsychiatric symptoms or aggravation of those symptoms. Antipsychotics should be prescribed after careful consideration to avoid adverse effects in persons with Parkinson's disease.

Topics: Antipsychotic Agents; Case-Control Studies; Clozapine; Hospitalization; Humans; Parkinson Disease; Quetiapine Fumarate

Topics: Clozapine; Humans; Neurodegenerative Diseases; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; United States

Dopamine receptor blocking atypical antipsychotic (DRB-AAP) use has previously been associated with increased adverse effects and mortality risk among persons with Parkinson disease (PD). Pimavanserin, the only AAP indicated for PD psychosis in the U.S., is a serotonin receptor inverse agonist/antagonist with no known DRB activity. Early observational data have reported inconsistent findings regarding mortality risk associated with pimavanserin. The objective of this study was to estimate all-cause mortality risks of pimavanserin as compared to DRB-AAPs.. We conducted a retrospective cohort study using a large U.S. commercial insurance database. Cox proportional hazards models were used to compare all-cause mortality risks between propensity score-matched groups of PD patients who were new users of pimavanserin or a DRB-AAP, further dividing DRB-AAPs into preferred (quetiapine, clozapine) and non-preferred (other remaining AAPs).. We identified 775, 4,563, and 1,297 individuals on pimavanserin, preferred, and non-preferred DRB-AAPs, respectively. There was no difference in mortality risk for pimavanserin vs. preferred DRB-AAPs [adjusted hazard ratio (aHR) 0.99, 95% CI: 0.81-1.20], or pimavanserin vs. non-preferred DRB-AAPs (aHR 0.98, 95% CI: 0.79-1.22) in intention-to-treat analyses.. Mortality risk among PD patients using AAPs did not differ by antipsychotic drug categorization based on mechanism of action. Research on the comparative efficacy and morbidity of AAPs, and the mortality associated with psychosis itself is needed to guide clinical decision-making in the PD population.

Topics: Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Serotonin; Retrospective Studies

Previous studies have assessed antipsychotic use after Parkinson's disease (PD) diagnosis, but incident antipsychotic use before PD diagnosis is unknown. The objective is to study the incidence of antipsychotic use among community-dwelling persons with and without PD 10 years before and after the PD diagnosis.. The study was based on the nationwide register-based FINPARK-study including 20,994 persons with PD (diagnosed 1996-2015) and 142,944 comparison persons who had not used antipsychotics during one-year washout before the follow-up. PD was diagnosed according to the United Kingdom's Parkinson's disease Society Brain Bank's criteria. Antipsychotic initiations in six-month time-windows was assessed.. 26.9% (n = 5,654) of people with PD initiated antipsychotics in comparison to 9.7% (n = 13,887) of people without PD during the entire follow-up. The incidence rate increased in people with PD approximately four years before the PD diagnosis. The most commonly initiated antipsychotic was quetiapine (n = 3,642, 64.4%) in persons with PD and risperidone (n = 5,232, 37.7%) in comparison persons. The initiation rates were higher in persons with PD before (6.5 and 3.0/1000 person-years for persons with and without PD, respectively, incidence rate ratio 2.18, 95%CI 2.03-2.33) and after the index date (43.3 and 11.7/1000 person-years for persons with and without PD, respectively, IRR 3.70, 95%CI 3.57-3.83).. Persons with PD have symptoms treated with antipsychotics both before and after diagnosis. Psychotic symptoms may be challenging to recognize as prodromal symptoms since they can occur years before the motor symptoms and thus, they cannot be clinically associated with the diagnosis of PD.

Topics: Antipsychotic Agents; Cohort Studies; Humans; Incidence; Parkinson Disease; Quetiapine Fumarate; Risperidone

Nausea and vomiting are common in the palliative demographic and can significantly affect quality of life. Initial management strategies involve tailoring antiemetic selection to the underlying cause. Whilst in refractory cases, management is often switched to a broader spectrum antipsychotic agent (such as levomepromazine or olanzapine). Yet in individuals with idiopathic Parkinson's disease antiemetics which antagonize central dopamine are avoided, as they have the potential to exacerbate motor control or even precipitate Parkinsonism-hyperpyrexia syndrome. Consequently, antiemetic options for patients with idiopathic Parkinson's disease are limited. This is the first report of quetiapine being successfully used for the management of nausea and vomiting in an individual with idiopathic Parkinson's disease.

Topics: Humans; Nausea; Parkinson Disease; Quality of Life; Quetiapine Fumarate; Vomiting

Current treatments for Parkinson's disease (PD) provide only symptomatic relief, with no disease-modifying therapies identified to date. Repurposing FDA-approved drugs to treat PD could significantly shorten the time needed for and reduce the costs of drug development compared with conventional approaches. We developed an efficient strategy to screen for modulators of β-glucocerebrosidase (GCase), a lysosomal enzyme that exhibits decreased activity in patients with PD, leading to accumulation of the substrate glucosylceramide and oxidized dopamine and α-synuclein, which contribute to PD pathogenesis. Using a GCase fluorescent probe and affinity-based fluorescence polarization assay, we screened 1280 structurally diverse, bioactive, and cell-permeable FDA-approved drugs and found that the antipsychotic quetiapine bound GCase with high affinity. Moreover, quetiapine treatment of induced pluripotent stem cell-derived (iPSC-derived) dopaminergic neurons from patients carrying mutations in GBA1 or LRRK2 led to increased wild-type GCase protein levels and activity and partially lowered accumulation of oxidized dopamine, glucosylceramide, and α-synuclein. Similarly, quetiapine led to activation of wild-type GCase and reduction of α-synuclein in a GBA mutant mouse model (Gba1D409V/+ mice). Together, these results suggest that repurposing quetiapine as a modulator of GCase may be beneficial for patients with PD exhibiting decreased GCase activity.

Topics: alpha-Synuclein; Animals; Antipsychotic Agents; Dopaminergic Neurons; Drug Evaluation, Preclinical; Drug Repositioning; Glucosylceramidase; Glucosylceramides; Humans; Induced Pluripotent Stem Cells; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mice; Parkinson Disease; Parkinsonian Disorders; Quetiapine Fumarate

The study presents a case of a 64-year-old patient with diagnosed Parkinson's disease and coexisting REM sleep disorders (RBD) confirmed in a polysomnographic examination. In this patient, the use of supplementary therapy - quetiapine (50mg/daily) - due to psychotic disorders, resulted in speech disorders with sensory-motor mixed aphasia type. Aphasia occurred on the fourth day after beginning the treatment with atypical neuroleptic. In MRI examination of the head, no "fresh" cerebral ischemia was found. No focal status epilepticus was reported in the video EEG trial. Results. Complete cure occurred after discontinuation of quetiapine administration. Conclusions. Due to the above, the side-effects of quetiapine treatment were assumed as the cause of focal neurological disorders.

Topics: Antipsychotic Agents; Aphasia; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Topics: Antipsychotic Agents; Follow-Up Studies; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

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

This retrospective cohort study was performed to investigate the association between risperidone and deteriorating performance in walking and dressing in subjects with Parkinson's disease using the Japanese Diagnosis Procedure Combination data. These data include inpatient claims including information from the time of admission to discharge from 89 acute phase National Hospitals in Japan. The data were evaluated by implementing the inverse probability of treatment weighting, using propensity scores estimated from the clinical characteristics of subjects prescribed risperidone or quetiapine. The generalized estimation equation was used to estimate the adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). In total, 304 subjects were eligible for participation, and were hospitalized between April 2012 and March 2017 (108 and 196 for risperidone and quetiapine groups, respectively). The performance of walking deteriorated at discharge, with 22.2% and 10.2% recorded at admission for the risperidone and quetiapine groups (aRR, 1.7; 95% CI, 0.9 to 3.4), respectively. The performance of dressing also deteriorated: 24.1% and 10.7% in the risperidone and quetiapine groups (aRR, 1.9; 95% CI, 1.04 to 3.7), respectively. These results suggest an association between risperidone and deteriorating performance in dressing in subjects with Parkinson's disease in comparison with quetiapine.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Cohort Studies; Female; Humans; Male; Parkinson Disease; Quetiapine Fumarate; Retrospective Studies; Risperidone; Walking

Topics: Antipsychotic Agents; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Topics: Antipsychotic Agents; Female; Hallucinations; Humans; Middle Aged; Parkinson Disease; Quetiapine Fumarate; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Female; Humans; Male; Middle Aged; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Survival Analysis; Treatment Outcome; Urea

Psychotic disorders in Parkinson's disease (PDPD) are common and significantly influence the quality of life and disability level. The pathogenesis of PDPD is complex and not yet fully understood. Taking into consideration the features of the Parkinson's disease (usually older patients with a risk of cognitive decline), and the pharmacodynamics of the antiparkinsonian and traditional antipsychotic drugs, the management of PDPD is a challenging issue of clinical neurology and psychiatry. In this systematic review, scientific publications for the period 2014-2016 were analyzed within two bibliographic databases: MEDLINE/PubMed and eLIBRARY.RU. Additionally, the guidelines of the International Parkinson and Movement Disorders Society, American Academy of Neurology and European Academy of Neurology were included in the analysis. Clozapine is recommended to use in the treatment of PDPD, quetiapine is possible to use, pimavanserin will probably become a remedy of choice. Nonpharmacological approaches have positive effects on the general condition of the patients with PDPD, however the efficacy of such approaches to treat psychosis is unclear.. Психотические расстройства при болезни Паркинсона (ПРБП) отмечаются у большого числа пациентов. Они оказывают значительное влияние на качество жизни и уровень инвалидизации. Патогенез ПРБП является сложным и до конца не изученным. Принимая во внимание специфику БП (как правило, пациенты пожилого возраста с риском появления когнитивных нарушений), а также фармакодинамические особенности антипаркинсонических и классических антипсихотических средств, лечение ПРБП требует особого внимания неврологов и психиатров. Представлен систематический обзор, в котором обобщены результаты научных публикаций за период 2014-2016 гг. в двух библиографических базах данных: MEDLINE/PubMed и eLIBRARY.RU, а также клинических рекомендаций Международного общества болезни Паркинсона и нарушений движения, Американской и Европейской академий неврологии. Из антипсихотических средств клозапин является препаратом, рекомендованным к применению, кветиапин - препарат, который признается возможным к применению, пимавансерин, вероятно, станет одним из препаратов выбора в терапии ПРБП. Нефармакологические методы лечения оказывают положительный эффект в плане улучшения общего состояния пациентов с ПРБП, однако их эффективность по лечению собственно ПРБП остается неясной.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Urea

Capgras delusion is a delusional misidentification syndrome, in which the patient is convinced that someone that is well known to them, usually a close relative, has been replaced by an impostor or double. Although it has been frequently described in psychotic syndromes, including paranoid schizophrenia, over a third of the documented cases of Capgras delusion are observed in patients with organic brain lesions or neurodegenerative disease, including Parkinson's Disease. Variants of Capgras involving animals or inanimate objects have also been described. The etiology of Capgras in Parkinson's remains unclear, but may arise from a combination of factors, such as frontal lobe dysfunction and dopaminergic medication.. We present the case of a 53-year old right-handed female with Parkinson's disease who developed Capgras delusion during treatment with dopamine agonists and Levodopa/Carbidopa. She became convinced that her pet dogs and the plants in her garden had been substituted by identically looking ones. Our patient was initially treated with Quetiapine, with no improvement, and subsequently treated with Clozapine, which lead to partial regression of her symptoms. Neuropsychological Evaluation showed Mild Cognitive Impairment in Executive Functions.. Given the clinical history, onset and evolution of symptoms we believe our patient's delusion resulted from the overlap of dopaminergic medication and Mild Cognitive Impairment in executive functions. Zoocentric Capgras, the variant we describe, has been rarely described in scientific literature, and we believe it is of interest due to its unusual characteristics.

Topics: Animals; Antiparkinson Agents; Antipsychotic Agents; Capgras Syndrome; Carbidopa; Clozapine; Cognitive Dysfunction; Delusions; Dibenzothiazepines; Dogs; Dopamine Agonists; Drug Therapy, Combination; Female; Humans; Levodopa; Parkinson Disease; Pets; Plants; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bipolar Disorder; Female; Humans; Middle Aged; Parkinson Disease; Quetiapine Fumarate

Electroconvulsive therapy cannot proceed safely unless blood pressure is within the reference range. Finding the cause of very high or low blood pressure can be very difficult, time consuming, and expensive. We suggest a more valid and reliable time to check blood pressure. This is highlighted in the case of a man that became riddled with iatrogenic complications and needless treatments.

Topics: Aged; Anesthesia; Antiparkinson Agents; Antipsychotic Agents; Blood Pressure; Depressive Disorder, Major; Dibenzothiazepines; Electroconvulsive Therapy; Humans; Hypertension; Iatrogenic Disease; Male; Parkinson Disease; Quetiapine Fumarate; Recurrence

Punding, a peculiar stereotyped behavior characterized by intense fascination with complex, excessive, non-goal-oriented, repetitive activities, is a quite rare condition complicating Parkinson's disease (PD). It is triggered by dopaminergic therapy and could have a strong impact on patient quality of life. No study has specifically investigated medical management of this condition, and only a few anecdotal reports have provided therapeutic hints. Given the suggested similarities to drug-induced dyskinesias, we have previously suggested a multistep algorithm for management of punding. We conducted a prospective open-label study on ten PD punders aimed at testing its validity. In two cases, reduction of levodopa therapy was efficacious; amantadine was effective in controlling punding in four cases; in the remaining cases, quetiapine was employed, with mild efficacy in two cases.

Topics: Adult; Aged; Algorithms; Amantadine; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Prospective Studies; Quetiapine Fumarate; Stereotypic Movement Disorder

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate; Rhabdomyolysis

Topics: Antipsychotic Agents; Dibenzothiazepines; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Delusional jealousy or Othello syndrome (OS) is a well-described psychiatric disorder with paranoid features reported in both organic and functional psychoses. In organic psychoses, the disorder occurs more frequently among chronic male alcoholics and in demented patients. To date, only 2 anecdotal cases of OS have been reported in Parkinson disease (PD) during dopaminergic treatment.. To investigate the presence of OS in PD patients and to study the relationship between dopaminergic treatment, avoiding the possible influence of dementia.. Five hundred sixty-three PD patients without dementia encountered in our movement disorders practice were included in the study. All patients who developed OS were studied. Relationships between clinical and familial history and dopaminergic therapy and OS were assessed.. Six patients with OS were identified. They were all male, with a relatively recent diagnosis of PD characterized by mild-moderate motor deficit. Dopaminergic treatment had been prescribed at low dosages. Neither confusional states (including agitated confusion) nor delirium were associated with OS. The disorder became manifest mainly at time of introduction/increment of antiparkinson treatment. Invariably, OS decreased or receded after reduction/suspension of the antiparkinson drug and prescription of an atypical neuroleptic, usually clozapine or quetiapine.. We hypothesize that nondemented PD patients affected by OS do not necessarily present with severe motor complications and may well have a biologic predisposition for psychiatric disorders. In our opinion this paranoid delusion is rarely considered in PD.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Delusions; Dementia; Dibenzothiazepines; Humans; Jealousy; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate; Retrospective Studies; Schizophrenia, Paranoid

Topics: Aged, 80 and over; Antipsychotic Agents; Dementia; Dibenzothiazepines; Dystonia; Humans; Male; Parkinson Disease; Psychomotor Agitation; Quetiapine Fumarate

Topics: Aged; Dibenzothiazepines; Female; Hallucinations; Humans; Parkinson Disease; Quetiapine Fumarate

Topics: Aged; Antipsychotic Agents; Anxiety; Depression; Dibenzothiazepines; Dopamine Agonists; Drug Therapy, Combination; Female; Humans; Parkinson Disease; Quetiapine Fumarate; Secondary Prevention

Atypical antipsychotics (AA) are generally associated with weight gain. We determined body mass index (BMI) change in Parkinson's disease (PD) before and after taking AA and compared against PD controls and Alzheimer's disease (AD) patients on AA. In 66 consecutive PD subjects started on AA who had accurate weights for more than 6 months before and after initiation of AA, we compared weight change before and after AA use, against a control group of sixty-one sex-matched PD subjects, and against twenty-eight AD subjects taking AA. A linear regression model was created to compare weight changes. Fifty-nine PD subjects had complete data, quetiapine (n=53) and clozapine (n=6). The mean BMI change in the period before starting AA was 0.00 kg/m(2)/month over 1.95+/-1.41 years. After starting AA, subjects lost 0.03 kg/m(2)/month (95% CI 0.62-1.21, P<0.0001), comparing PD before AA to the same PD patients after AA. In 61 PD controls, the mean BMI loss was 0.01 kg/m(2)/month (95% CI 0.15-0.94, P=0.007) comparing PD on AA vs. PD controls. The BMI for 28 AD subjects on AA increased 0.01 kg/m(2)/month (95% CI 0.26-0.83, P<0.0001), comparing PD on AA vs. AD on AA. The weight loss seen in the PD/AA group, compared to AD, suggest uniquely altered weight homeostasis in PD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Body Mass Index; Body Weight; Case-Control Studies; Clozapine; Confidence Intervals; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Odds Ratio; Parkinson Disease; Quetiapine Fumarate

"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.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Laughter; Levodopa; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Parkinson Disease, Secondary; Piperazines; Psychoses, Substance-Induced; Quetiapine Fumarate; Thiazoles

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Gambling; Humans; Male; Parkinson Disease; Pergolide; Quetiapine Fumarate

Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

Topics: Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Dibenzothiazepines; Humans; Leptin; Lipids; Lipoproteins; Olanzapine; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone

To determine whether psychiatrically stable patients with a history of drug-induced psychosis could be successfully weaned off their antipsychotic drug, we offered consecutive Parkinson disease (PD) patients on quetiapine or clozapine, who were free of any on-going psychosis, to be slowly weaned off their antipsychotic drug. Before the study was aborted 6 PD patients (mean age, 78 years) with an average antipsychotic exposure of 20 months (5 on quetiapine, 1 on clozapine) were enrolled. After the antipsychotic agent was discontinued, psychosis recurred in 5 of 6 patients. In 3 patients the "rebound psychosis" was worse than the original psychotic episode and required subsequent higher antipsychotic medication doses.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Parkinson Disease; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Time Factors

Topics: Antipsychotic Agents; Clozapine; Dibenzothiazepines; Humans; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate

We report a 32-year-old male patient with early-onset Parkinson's disease who exhibited abnormally increased writing activity. The patient displayed a disabling and pronounced increased writing activity, filling up to 10 pages or more per day in a notebook, and spending more than 12 h writing. In general, there was not much meaning in most of the writing, though there was a particular preference in tabulating the names of various sport and TV personalities. The writing activity gradually diminished following treatment with quetiapine hydrochloride, an anti-psychotic agent, at 25 mg/day. Although the pathophysiological mechanism underlying the increased writing is unclear, we believe it should be regarded as a form of punding or stereotyped behavior that has been suggested to be associated with dopaminergic therapy in Parkinson's disease.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Parkinson Disease; Quetiapine Fumarate; Stereotyped Behavior; Writing

We report a patient with advanced Parkinson's disease (PD) who developed a recurrence of major depression with psychotic features after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Electroconvulsive therapy (ECT) dramatically improved the depression without shifting electrode position or damaging the DBS hardware. This case suggests that ECT can be a safe and effective option for severe depression in PD patients treated with STN DBS.

Topics: Antiparkinson Agents; Antipsychotic Agents; Deep Brain Stimulation; Depressive Disorder, Major; Dibenzothiazepines; Electroconvulsive Therapy; Female; Humans; Levodopa; Magnetic Resonance Imaging; Middle Aged; Parkinson Disease; Quetiapine Fumarate; Subthalamic Nucleus

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.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Delusions; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Parkinson Disease; Quetiapine Fumarate

Quetiapine has been suggested to be useful for the treatment of psychosis in patients with Parkinson's disease without prominent deterioration of motor functions. We present two patients with Parkinson's disease in whom administration of quetiapine for drug-induced psychosis caused characteristic stereotyped behaviors or punding. Since stereotyped behaviors are usually associated with excessive dopaminergic activity, it is clinically important to note that stereotyped behaviors or punding may be induced by an atypical antipsychotic drug for the treatment of psychosis in patients with Parkinson's disease.

Topics: Aged; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate; Stereotyped Behavior

Young onset Parkinson's disease (YOPD) is defined as idiopathic Parkinson's disease (IPPD) occurring in people between 21 and 40 years of age; it strikes approximately 5% of Parkinson's patients. YOPD has earlier onset of motor complications than later onset Parkinson's disease. Motor complications and disease progression are responsible for devastating morbidity. Current medical and surgical treatments can dramatically ameliorate motor complications and help maintain function and employment. Patient education, support, and advocacy provided by nursing staff can influence the treatment options for these patients, having a significant effect on the future course of the disease. This case history documents the course of a YOPD patient with unusually severe motor complications. He is the only patient at Puget Sound Neurology ever to develop rhabdomyolysis due to dyskinesias. Following bilateral subthalamic nucleus deep brain stimulation, his Parkinson's symptoms have improved dramatically, and his motor complications are significantly improved.

Topics: Activities of Daily Living; Adult; Age of Onset; Amantadine; Antiparkinson Agents; Carbidopa; Combined Modality Therapy; Deep Brain Stimulation; Dibenzothiazepines; Disease Progression; Dyskinesias; Humans; Levodopa; Male; Motor Skills; Nurse's Role; Parkinson Disease; Patient Advocacy; Patient Education as Topic; Quality of Life; Quetiapine Fumarate; Rhabdomyolysis; Severity of Illness Index; Social Support; Treatment Outcome

To evaluate the long-term efficacy and tolerability of quetiapine for psychosis among parkinsonian patients, a retrospective analysis of all parkinsonian patients taking quetiapine for psychosis in a single movement disorders center was carried out. Demographic data, including type and severity of psychosis, presence of dementia, treatment response, before and after Unified Parkinson's Disease Rating Scale (UPDRS)-motor scores and Hoehn and Yahr (H&Y) scale were obtained. One hundred six parkinsonian patients with a mean age of 76.6 years were on an average levodopa (L-dopa) dose of 415 mg/d. Seventy-eight of 106 (74%) remained on quetiapine for a mean duration of 15 months at an average dose of 60 mg per day. Eighty-seven (82%) patients had partial or complete resolution of their psychosis whereas 19 (18%) patients had no improvement on quetiapine. Motor worsening was noted in 34 (32%) patients but was uncommonly sufficient to warrant quetiapine discontinuation. More quetiapine non-responders were noted to be demented, delusional, and experienced threatening psychosis but only the presence of dementia remained significant on multivariate analysis (OR = 11.6; 95% CI = 1.4-92.9). Also, patients who developed motor worsening while on quetiapine tended to be more demented (P = 0.07).

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Drug Tolerance; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Levodopa; Male; Outcome Assessment, Health Care; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Severity of Illness Index

Due to its low profile for extrapyramidal side-effects, quetiapine has become an alternative to clozapine in the treatment of dopamimetic psychosis in patients with Parkinson's disease (PD). We describe the case of a patient with PD who developed severe akathisia, a common complication with classical antipsychotics, with quetiapine.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate

Psychosis characterized by hallucination or delusion, which occurs during drug therapy of parkinsonian patients, is one of the limiting factors for the control of motor symptoms or complications. In the present study, we encountered three patients with Parkinson's disease (PD) at advanced stages; all three patients had severe psychosis and severe wearing-off phenomenon and one had severe orthostatic hypotension. Their psychotic symptoms were successfully treated by administration of quetiapine, resulting in the favorable control of motor fluctuations and elevation of therapeutic levels unless any aggravation of parkinsonism occurs. Although the measure against drug-induced psychosis is principally a reduction of the doses or withdrawal of causative drugs, the effective use of antipsychotic drugs, such as quetiapine, is helpful to suppress psychosis and allow the patient to adjust to antiparkinsonian drugs for the control of symptoms other than psychosis.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Cabergoline; Dibenzothiazepines; Ergolines; Hallucinations; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate

Recently, several small studies have indicated that quetiapine may be useful in the treatment of drug-induced psychosis in patients with PD. However, there have been questions related to atypical antipsychotic therapy and patient selection and how that may affect response and tolerability, especially worsening of the motor symptoms of PD. In particular, the presence or absence of dementia seems to be important. The aim of this study was to evaluate the effect of quetiapine on psychosis and motor symptoms in PD patients with and without dementia. A retrospective record review of patient responses to quetiapine was conducted. Response of psychosis was assessed through patient and caregiver interviews. Motor symptom change in relation to this therapy was assessed by patient and caregiver interviews and completion of the motor portion of the Unified Parkinson's Disease Rating Scale (UPDRSm). Analysis was performed by comparing psychosis and motor feature measures from before and after therapy for the group as a whole and for demented and nondemented subgroups, using nonparametric tests and Fisher's exact test. Forty-three consecutively treated PD patients were evaluated. The mean dose of quetiapine was 54 mg per day and the duration of therapy was 10 months. Eighty-one percent of patients demonstrated partial or complete amelioration of psychosis. Five patients (13%) experienced a worsening of PD motor symptoms, which was corroborated by changes seen in UPDRSm. When the group was examined as a whole, no significant change in UPDRSm score was noted. When demented (n = 20) and nondemented (n = 19) patients were compared, improvement in psychosis occurred in similar numbers of patients, but a significant difference in the numbers of patients who experienced a worsening of motor symptoms was seen (P < 0.02, Fisher's exact test). All five patients who complained of motor worsening were in the demented group. UPDRSm score after therapy tended to be worse in the demented group (P = 0.55, Mann-Whitney U test). There was no significant change in the levodopa dose. Approximately 80% of patients chose to continue therapy. We conclude that quetiapine is effective in improving psychosis in approximately 80% of PD patients both with and without dementia. Patients with dementia seem to have a higher propensity for worsening of motor symptoms.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Mental Status Schedule; Middle Aged; Motor Skills; Neurologic Examination; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate; Retrospective Studies

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Hallucinations; Humans; Male; Parkinson Disease; Quetiapine Fumarate

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Cost of Illness; Dibenzothiazepines; Humans; Nursing Homes; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; United States

Although quetiapine is the antipsychotic of choice for the psychosis associated with Parkinson's disease (PD) and often is also helpful for sleep, we report two cases of quetiapine-induced extrapyramidal side effects. The patients described were unusual in their frailty and severity of illness and may not represent the majority of patients with PD.

Topics: Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Ocular Motility Disorders; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Humans; Levodopa; Male; Olanzapine; Parkinson Disease; Pirenzepine; Psychoses, Substance-Induced; Quetiapine Fumarate; Treatment Outcome

Topics: Aged; Clozapine; Dibenzothiazepines; Humans; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate; Retrospective Studies

There are many difficulties associated with the late stages of Parkinson's disease (PD), but psychosis and agitation may be the most disturbing for both patients and care givers, and often precipitate the pivotal decision for long-term nursing home placement. While the addition of antipsychotic drugs or the withdrawal of antiparkinsonian drugs may improve the behavioral problem, these strategies usually worsen the motor difficulties. Clozapine has been studied in PD for over a decade, and while it appears to be effective, there are safety and tolerability concerns associated with it. In addition, in New Jersey, Medicaid no longer pays for the home blood draws that are required for home-bound patients. This led to a situation in which we had patients who needed to stop clozapine and begin an alternative therapy. Because quetiapine seems particularly well suited to patients with PD based on in vitro and in vivo studies we have begun to try this medication in PD patients who need to stop clozapine. This article reports three case histories of patients with PD, confusion and dopamimetic psychosis who had been previously managed with clozapine and who were successfully switched to quetiapine. At doses from 12.5 to 150 mg/day quetiapine was well tolerated, resulting in behavioral improvement and no real increase in parkinsonism. These case histories raise the possibility that quetiapine may represent a viable alternative to clozapine in PD patients with dopamimetic psychosis and behavioral disturbances.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Confusion; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome