quetiapine-fumarate and Parkinsonian-Disorders

The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism.. Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias.. A total of 17,615 unique records were identified, and seven RCTs (total N=241) met inclusion criteria. Five RCTs were placebo controlled, and two compared quetiapine against clozapine. The mean study duration was 12 weeks, and the mean daily quetiapine dose was 103 mg per day (range, 12.5-300 mg). In four of five placebo-controlled RCTs, quetiapine failed to demonstrate significant improvement of psychosis in parkinsonism compared with placebo. In two clozapine-comparator RCTs, quetiapine was better tolerated but no more effective than clozapine. Across all RCTs, the mean completion rates for quetiapine, clozapine, and placebo were 66%, 68.5%, and 66%, respectively. Quetiapine did not significantly worsen motor function.. The efficacy of quetiapine in RCTs for psychosis in parkinsonism is no better than that for placebo or clozapine. On the basis of novel data, clinicians should reevaluate traditional viewpoints on the benefits of quetiapine for psychosis in parkinsonism.

Topics: Antipsychotic Agents; Humans; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

Topics: Acute Disease; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dystonia; Humans; Indoles; Isoindoles; Parkinsonian Disorders; Quetiapine Fumarate; Receptors, Muscarinic; Receptors, Serotonin; Risperidone; Serotonin Antagonists; Syndrome; Thiazoles

Antipsychotic agents remain the most effective treatment for both acute and chronic schizophrenia. However, conventional antipsychotic agents are frequently associated with significant side effects including, perhaps most notably, extrapyramidal symptoms (EPS). The emergence of EPS can significantly compromise patient compliance with treatment and can have profound effects on long-term treatment outcomes. Providing effective symptom relief with minimal side effects and without inducing EPS is, therefore, a primary goal in the treatment of schizophrenia. Atypical antipsychotic agents are now regarded as first-line therapies for the treatment of schizophrenia because of their lower propensity to induce EPS compared with conventional antipsychotics, and evidence exists that these agents are associated with a lower relapse rate, which perhaps reflects an improvement in patient compliance.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dystonia; Female; Humans; Male; Movement Disorders; Parkinsonian Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To compare the efficacy and adverse effect profiles of 2 widely used atypical antipsychotics in the short-term phase of first-episode schizophrenia in patients who were treatment-naive. A secondary objective was to establish the effective dose of these drugs in this context.. A total of 72 patients with a first episode of schizophreniform psychosis (schizophrenia spectrum disorder) with less than 2 weeks of exposure to antipsychotic medication were randomized to quetiapine or risperidone in a single-blind 12-week controlled trial. Psychopathologic diagnoses and adverse effects were assessed by blinded raters at 4 weekly intervals. Medication was administered by a specialized clinical team following dosing guidelines. Data were analyzed using an intention-to-treat paradigm.. Both quetiapine and risperidone were associated with a reduction in immediate symptoms and relatively few adverse effects other than weight gain. There was no statistically significant difference between the 2 compounds in adverse effects, relative efficacies, or adherence to treatment. The median (SD) time to cessation for patients randomized to quetiapine was 65.3 (41.85) days and that for risperidone was 82.5 (44.88) days. There was no statistically significant difference between time to discontinuation for the 2 compounds. The mean daily doses prescribed were 375 mg of quetiapine and 2.72 mg of risperidone.. Quetiapine and risperidone are both effective treatments in first-episode schizophrenia at doses lower than those used in patients with long-term schizophrenia and are similar in efficacy and the incidence of adverse effects.

Topics: Adult; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Parkinsonian Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Single-Blind Method; Time Factors; Treatment Outcome; Young Adult

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

No safe, tolerated, and effective treatment for Parkinson's disease psychosis (PDP) is available; however, clozapine and quetiapine are often used off-label. An ideal PDP drug should have a therapeutic window that alleviates psychotic symptoms at doses that allow for maintained motor control and do not cause sedation. The present study determined the effective doses of quetiapine, clozapine, and the nondopaminergic, selective 5-HT2A inverse agonist/antagonist, pimavanserin, in an animal model of PDP and compared them with the doses that caused dopamine blockade and sedation. Augmented amphetamine-induced locomotion in rats with bilateral substantia nigra lesions was used to assess antipsychotic efficacy, whereas blockade of apomorphine-induced rotations in rats with unilateral 6-hydroxydopamine lesions was used to assess antidopaminergic action and reduction in spontaneous locomotion was used to assess sedation. The estimated therapeutic ratios for clozapine and quetiapine varied between 0.81 and 3.3. In contrast, the estimated therapeutic ratios for pimavanserin were at or above 170. These results suggest that a selective 5-HT2A inverse agonist/antagonist, such as pimavanserin, may provide distinct advantages compared with clozapine or quetiapine as a therapy for PDP.

Topics: Amphetamine; Animals; Antiparkinson Agents; Antipsychotic Agents; Apomorphine; Clozapine; Dopamine; Dose-Response Relationship, Drug; Male; Parkinsonian Disorders; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Urea

: The use of antipsychotic medications is associated with an increased risk of death in older adults with dementia. The risk of death in patients with preexisting parkinsonism who receive antipsychotic drugs is not known.. : Using a nested case-control design, we examined the risk of death within 30 days of newly starting antipsychotic medications among people with Parkinsonism aged 70 years and older in Ontario, Canada. Data were obtained from Ontario's healthcare administrative databases.. : Among 5,391 individuals with parkinsonism who died during the study period (2002-2008) and a matched comparison group of 25,937 who were still alive, individuals exposed to atypical antipsychotic drugs had a higher risk of death (unadjusted odds ratio [OR] = 2.8, 95% CI: 2.1-3.8, adjusted OR: 2.0, 95% CI: 1.4-2.7). Results were similar for quetiapine use compared with no antipsychotic use (unadjusted OR: 2.5, 95% CI: 1.6-4.0, adjusted OR = 1.8, 95% CI: 1.1-3.0). Typical antipsychotics were associated with an increased odds of death compared with atypical antipsychotics (unadjusted OR = 2.4, 95% CI 1.1-5.2, adjusted OR = 2.4, 95% CI: 1.1-5.7).. : Individuals with parkinsonism who are newly prescribed antipsychotic medications have a higher risk of death within 30 days than those who do not start these medications. Although it is not possible to establish causality, the results suggest an increased risk. It is important to be vigilant for accompanying serious medical conditions that may increase mortality in individuals requiring treatment with antipsychotics and to consider alternative approaches to treating psychosis, agitation, and aggression in this population.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cohort Studies; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Ontario; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk; Risperidone

The present paper reports on a 68-year-old man with a 10-year history of parkinsonism who developed hallucinations and delusions after admission to an intensive care unit for the treatment of organophosphate intoxication. His initial diagnosis was delirium. On the basis of brain computed tomography findings and clinical symptoms, we diagnosed drug-induced psychosis in parkinsonism with multiple cysts in the bilateral striata.

Topics: 3-Iodobenzylguanidine; Aged; Antiparkinson Agents; Antipsychotic Agents; Brain Ischemia; Delirium; Delusions; Diagnosis, Differential; Dibenzothiazepines; Dominance, Cerebral; Drug Therapy, Combination; Encephalomalacia; Hallucinations; Humans; Levodopa; Magnetic Resonance Imaging; Male; Neostriatum; Neurologic Examination; Organophosphate Poisoning; Parkinsonian Disorders; Psychoses, Substance-Induced; Quetiapine Fumarate; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Female; Hallucinations; Humans; Parkinsonian Disorders; Psychomotor Agitation; Quetiapine Fumarate; Risperidone

Frontotemporal dementia (FTD) often presents with behavioural changes warranting treatment with antipsychotic medications. It is known that patients with Lewy body dementia are sensitive to developing extrapyramidal symptoms (EPS) from these medications. This has not been emphasized in FTD. We report three patients with FTD that developed parkinsonism and prominent antecollis after treatment with newer antipsychotics, including olanzapine, risperidone and quetiapine. Patients with FTD might have increased sensitivity to antipsychotic medications as with Lewy body dementia. Although newer antipsychotics have favourable side effect profiles, there is increasing evidence that EPS develop more frequently than previously thought.

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Dibenzothiazepines; Dystonia; Humans; Male; Middle Aged; Neck Muscles; Olanzapine; Parkinsonian Disorders; Quetiapine Fumarate; Risperidone

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

A 52-year-old patient with treatment-resistant paranoid schizophrenia developed severe parkinsonian features after more than 20 years of antipsychotic drug therapy. The role of this therapy was thought to have been a contributing factor to the patient's clinical presentation, although Parkinson's disease could not be ruled out. Originally, parkinsonian symptoms developed acutely and progressed to hand tremor, sialorrhea, upper body rigidity, masked facies, striatal hand, bradykinesia, and a severe, unsteady, shuffling gait. Tremor and rigidity were the only parkinsonian symptoms that responded to anticholinergic therapy. After converting from a first- to a second-generation antipsychotic drug, the patient maintained psychiatric stability, with some improvement in motor functioning-most notably decreased upper body rigidity. Our findings are consistent with the literature on quetiapine therapy in patients with Parkinson's disease in terms of adequately controlling psychosis without worsening motor symptoms. The difference, however, was that in most cases reported, psychotic features were the result of dopamine-enhancing treatments and not schizophrenia.

Topics: Antipsychotic Agents; Chronic Disease; Dibenzothiazepines; Humans; Male; Middle Aged; Parkinsonian Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroconvulsive Therapy; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Neurologic Examination; Parkinsonian Disorders; Quetiapine Fumarate; Risk Factors

In the present open prospective study the effects of quetiapine were investigated in two elderly patients with parkinsonism and psychosis. Treatment induced a marked antipsychotic effect that coincided with an improvement of general motor functioning. These findings support the idea that quetiapine may be preferentially of use in the elderly with parkinson's disease and psychotic symptoms.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

The contribution of serotoninergic mechanisms to motor dysfunction in Parkinson's disease (PD) has yet to be fully elucidated. Recent clinical observations increasingly suggest that drugs able to block serotonin 5HT2A/C receptors can benefit patients with certain extrapyramidal movement disorders. To further explore the roles of these and other neurotransmitter receptors in the pathogenesis of parkinsonian signs and levodopa-induced dyskinesias; we evaluated the effects of quetiapine, an atypical antipsychotic with 5HT2A/C and D2/3 antagonistic activity, on motor behavior in 6-hydroxydopamine-lesioned rats and MPTP-lesioned nonhuman primates. In hemiparkinsonian rats, quetiapine (5 mg/kg, po) reversed the shortened motor response to levodopa challenge produced by 3 weeks of twice-daily levodopa treatment (P < 0.01). Quetiapine (5 mg/kg po) also normalized the shortened response to the acute injection of either a dopamine D1 receptor agonist (SKF 38392) or a D2 agonist (quinpirole) in rats that had received chronic levodopa treatment. Quetiapine had no effect on parkinsonian dysfunction when given alone or with levodopa to parkinsonian rats and monkeys. Quetiapine (4 mg/kg, po) did, however, substantially reduce levodopa-induced dyskinesias when coadministered with levodopa (P < 0.05). These results suggest that quetiapine could confer therapeutic benefits to patients with levodopa-induced motor complications. Moreover, our findings may indicate that 5HT2A/C receptor-mediated mechanisms, alone or in combination with other mechanisms, contribute to the pathogenesis of the altered motor responses associated with the treatment of PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Antipsychotic Agents; Behavior, Animal; Dibenzothiazepines; Disease Models, Animal; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Levodopa; Macaca fascicularis; Male; Motor Activity; Oxidopamine; Parkinsonian Disorders; Quetiapine Fumarate; Rats; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Serotonin; Serotonin Antagonists