piperidines and Hallucinations

Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.

Topics: Dementia; Hallucinations; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Urea

Topics: Animals; Antipsychotic Agents; Delusions; Hallucinations; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Urea

We discuss features of Parkinson's disease psychosis (PDP) including symptomology and pathophysiology. Treatment options, including non-pharmacologic strategies, dose reduction of offending agents, and the addition of non-dopaminergic antipsychotics, are addressed. The efficacy of second-generation antipsychotics and novel agents is examined.. Pimavanserin, a 5-HT

Topics: Antipsychotic Agents; Delusions; Hallucinations; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Serotonin 5-HT2 Receptor Antagonists; Urea

Sleep paralysis is a state of involuntary immobility occurring at sleep onset or offset, often accompanied by uncanny "ghost-like" hallucinations and extreme fear reactions. I provide here a neuropharmacological account for these hallucinatory experiences by evoking the role of the serotonin 2A receptor (5-HT

Topics: Animals; Dopamine; Hallucinations; Hallucinogens; Humans; Lysergic Acid Diethylamide; Neuropharmacology; Piperidines; Psilocybin; Receptor, Serotonin, 5-HT2A; Serotonin; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Sleep; Sleep Paralysis; Urea

To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson's disease psychosis (PDP).. A comprehensive PubMed search (1966 to January 2017) was conducted using the search terms Parkinson's disease psychosis, hallucinations, delusions, pimavanserin, and ACP-103. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling and website, and Clinicaltrials.gov.. All English-language trials evaluating pimavanserin in PDP were included. Data from review articles were included if relevant to clinical practice. One phase II and 3 phase III trials are discussed.. Pimavanserin was approved in April 2016 for the treatment of delusions and hallucinations of PDP. One phase II and 2 phase III trials reported no difference for primary outcomes when pimavanserin was compared with placebo. The pivotal phase III ACP-103-020 trial adapted a scale to target more specific symptoms prevalent in PDP and showed that least-squares mean differences of the total PD-adapted Scale for the Assessment of Positive Symptoms score were significantly improved for pimavanserin-treated patients as compared with placebo-treated patients (difference = -3.06; 95% CI [-4.91 to -1.20]; P = 0.0014]). Pimavanserin's adverse effect profile includes urinary tract infections, falls, peripheral edema, hallucinations, confusion, nausea, and headaches.. Pimavanserin is a novel 5-HT

Topics: Antiparkinson Agents; Antipsychotic Agents; Delusions; Hallucinations; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Urea

To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. We describe the regulatory and clinical issues important to the FDA's approval of this New Drug Application, with special focus on the risk-benefit balance. We also describe a new labeling feature that presents additional efficacy data to clinicians.. Data sets for all relevant clinical trials of pimavanserin and the Applicant's and FDA's analyses of these data were considered in this review. Data were available from 616 patients with Parkinson's disease with hallucinations and delusions who received at least 1 dose of pimavanserin, with a total exposure of 825 patient-years in the Parkinson's disease psychosis population.. Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease. In the Applicant's single pivotal trial, 80.5% of pimavanserin patients experienced at least some improvement in symptoms compared to 58.1% of patients taking placebo. Pimavanserin did not worsen motor function, an adverse effect commonly observed with other antipsychotics, probably because of a lack of consequential dopamine binding.. Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. Although pimavanserin appears to have a pharmacologic mechanism that is different from other atypical antipsychotics, concern remained that the increased risk of death seen with antipsychotic use in elderly demented patients, and described in all approved antipsychotic labels, would also occur with pimavanserin. Pimavanserin bears the same boxed warning about the risk of death associated with antipsychotic use in elderly patients with dementia.

Topics: Antipsychotic Agents; Delusions; Hallucinations; Humans; Parkinson Disease; Piperidines; United States; United States Food and Drug Administration; Urea

Parkinson's disease psychosis (PDP) may develop in up to 60% of Parkinson's patients and is associated with increased morbidity and mortality. It also correlates with depression and dementia, and can contribute to caregiver stress and burnout. Pimavanserin is the first FDA approved drug for the treatment of hallucinations and delusions associated with PDP. Areas covered: For this review, a MEDLINE literature search (via PubMed) and information provided by ACADIA Pharmaceuticals were used. This review will discuss the pathophysiology and current management of PDP. In addition, this review will focus on the rationales behind the development of pimavanserin, mechanism of action, pharmacokinetics, pharmacodynamics, and the clinical trials evaluating the efficacy and safety of pimavanserin. Last, the review will address the drug's package insert warning. Expert commentary: Pimavanserin, a 5HT2A receptor inverse agonist, is the first FDA approved drug for the treatment of PDP which has been shown to reduce psychosis in PD through its unique mechanism of action. Pimavanserin, does not worsen PD motor symptoms and has an acceptable safety profile. The development of pimavanserin as an antipsychotic opened a new therapeutic avenue in the treatment of PDP as well as targeting psychosis in other disorders such as Alzheimer's disease.

Topics: Antipsychotic Agents; Delusions; Drug Inverse Agonism; Hallucinations; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Serotonin 5-HT2 Receptor Agonists; Urea

Pimavanserin (Nuplazid™) is a selective and potent serotonin 2A (5-HT2A) receptor inverse agonist and antagonist developed by ACADIA Pharmaceuticals that has been approved in the US as a treatment for patients with hallucinations and delusions associated with Parkinson's disease psychosis. Up to 60 % of patients with Parkinson's disease may develop Parkinson's disease psychosis, which is associated with increased morbidity and mortality and has few treatment options. This article summarizes the milestones in the development of pimavanserin leading to this first approval for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis.

Topics: Antipsychotic Agents; Delusions; Drug Approval; Drug Discovery; Drug Evaluation, Preclinical; Hallucinations; Humans; Molecular Structure; Parkinson Disease; Piperidines; Randomized Controlled Trials as Topic; Serotonin 5-HT2 Receptor Agonists; Treatment Outcome; Urea

Charles Bonnet syndrome (CBS) is characterized by recurrent or persistent complex visual hallucinations that occur in visually impaired individuals with intact cognition and no evidence of psychiatric illness. Patients usually retain insight into the unreal nature of their hallucinations.3,4 CBS is often misdiagnosed, and predominantly affects elderly patients with vision changes (e.g., age-related macular degeneration, glaucoma, and cataract). While many require only the assurance of the benign nature of the hallucinations, nonpharmacological and pharmacological interventions have been reported to be useful in the treatment of CBS. This case involves an 83-year-old female, with a two-year history of CBS, who presented to the clinic with worsening visual hallucinations over the past few months. She was starting to lose insight into her hallucinations secondary to her new diagnosis of dementia. Several pharmacological agents were explored to determine the most appropriate choice for our patient. Ultimately, this patient was started on donepezil (reported to be successful in a CBS case report), which helped improve her cognitive function. At future follow-up visits, her hallucinations improved and her cognitive function stabilized. Pharmacists should be aware of CBS and its treatment options to properly assist physicians in the medication-selection process to alleviate distress experienced by patients with CBS. In patients who may benefit from pharmacological treatment, physicians should weigh the risks and benefits of the different treatment options. Donepezil can be a favorable option in CBS patients with Alzheimer's type dementia.

Topics: Aged, 80 and over; Cognition; Dementia; Donepezil; Female; Hallucinations; Humans; Indans; Nootropic Agents; Piperidines; Syndrome; Treatment Outcome; Vision Disorders

Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh) depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition.. A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia.. No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group.. Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly.. We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed.

Topics: Cholinesterase Inhibitors; Donepezil; Galantamine; Hallucinations; Humans; Indans; Phenylcarbamates; Piperidines; Rivastigmine; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To review the effect of cholinesterase inhibitors on the behavioural and neuropsychiatric symptoms of dementia and discuss the current clinical guidelines for the prescription of cholinesterase inhibitors in Australia.. This paper reports the case of a patient with clinical diagnosis of dementia with lewy bodies (DLB) who was referred to an old age psychiatry service for the treatment of severe visual hallucinations and behavioural problems.. Pharmacological treatment with olanzapine produced marked parkinsonism, agitation and confusion. A cholinesterase inhibitor, donepezil, was introduced. The introduction of donepezil was associated with cognitive improvement (mini-mental state examination [MMSE] increased from 23 to 27) and complete remission of behavioural symptoms.. That cholinesterase inhibitors may have a role in the management of behavioural symptoms of dementia and the current Australian PBS guidelines for prescribing cholinesterase inhibitors are clinically restrictive. This has clinical and ethical implications that need to be addressed by consumers, the medical community and regulating authorities.

Topics: Aged; Aged, 80 and over; Australia; Cholinesterase Inhibitors; Donepezil; Ethics; Hallucinations; Humans; Indans; Lewy Body Disease; Male; Mental Disorders; Piperidines

Topics: Aggression; Amenorrhea; Antipsychotic Agents; Drug Tolerance; Female; Hallucinations; Humans; Palmitic Acids; Phenothiazines; Piperidines; Pregnancy; Sulfonamides; Undecylenic Acids

Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HT. We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) at weeks 8 and 12 were randomly assigned in a 1:1 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end point, assessed in a time-to-event analysis, was a relapse of psychosis as defined by any of the following: an increase of at least 30% in the SAPS-H+D score and a CGI-I score of 6 (much worse) or 7 (very much worse), hospitalization for dementia-related psychosis, stopping of the trial regimen or withdrawal from the trial for lack of efficacy, or use of antipsychotic agents for dementia-related psychosis.. Of the 392 patients in the open-label phase, 41 were withdrawn for administrative reasons because the trial was stopped for efficacy; of the remaining 351 patients, 217 (61.8%) had a sustained response, of whom 105 were assigned to receive pimavanserin and 112 to receive placebo. A relapse occurred in 12 of 95 patients (13%) in the pimavanserin group and in 28 of 99 (28%) in the placebo group (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.73; P = 0.005). During the double-blind phase, adverse events occurred in 43 of 105 patients (41.0%) in the pimavanserin group and in 41 of 112 (36.6%) in the placebo group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin.. In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dementia; Double-Blind Method; Female; Hallucinations; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Parkinson Disease; Piperidines; Proportional Hazards Models; Psychotic Disorders; Recurrence; Urea

Deficits in the cholinergic system are pronounced in dementia with Lewy bodies (DLB) and are more severe in patients with visual hallucinations (VHs). The aim is to identify the occipital glucose metabolism patterns by positron emission tomography (PET) and the changes following donepezil treatment. 13 DLB patients with VHs were enrolled in the study. After the first FDG-PET study, 5 mg/day donepezil was administered orally, and a second PET study was performed 3 months later. After donepezil administration, VHs disappeared completely in 6 patients, and the PET studies revealed significantly decreased glucose metabolism in the medial occipital cortex. These results suggest that VHs in DLB were associated with impaired glucose metabolism in the medial occipital cortex. Donepezil treatment may modify regional glucose metabolism.

Topics: Aged, 80 and over; Donepezil; Female; Glucose; Hallucinations; Humans; Image Interpretation, Computer-Assisted; Indans; Lewy Body Disease; Male; Neuropsychological Tests; Nootropic Agents; Occipital Lobe; Piperidines; Positron-Emission Tomography

As cholinergic mechanisms may be at least partially responsible for hallucinations and delusions in Parkinson's disease (PD), we conducted an open study in 8 PD patients to assess the efficacy and tolerability of the cholinesterase inhibitor donepezil, 5 mg at bedtime for two months, in the treatment of these complications. Hallucinations and delusions improved significantly in all patients. Donezepil was overall well tolerated, but a deterioration in motor disability was noted in 2 out of 8 patients.

Topics: Aged; Aged, 80 and over; Basal Nucleus of Meynert; Cholinergic Fibers; Cholinesterase Inhibitors; Delusions; Donepezil; Female; Hallucinations; Humans; Indans; Male; Movement; Parkinson Disease; Piperidines; Sexual Dysfunctions, Psychological; Sleep Wake Disorders; Treatment Outcome

Five depot neuroleptics (fluphenazinedeconoate, fluspirilene, pipothiazinepalmitate, penfluridol and perphenazine-enanthate) were compared based on clinical trials in subacute and chronic schizophrenic patients. The psychopathological symptoms were documented by means of the AMP-system. Statistical analyses showed several differences between the effects of the five substances. The AMP-system proved a useful instrument to differentiate similar drugs.

Topics: Administration, Oral; Bipolar Disorder; Catatonia; Clinical Trials as Topic; Delayed-Action Preparations; Drug Evaluation; Female; Fluorobenzenes; Fluphenazine; Hallucinations; Hostility; Humans; Hydrocarbons, Halogenated; Hypochondriasis; Injections, Intramuscular; Methods; Paranoid Disorders; Perphenazine; Piperidines; Schizophrenia; Spiro Compounds; Sulfonamides; Time Factors; Tranquilizing Agents

A controlled study was made of penfluridol medication consisting of a single weekly oral dose of 30 mg in 30 patients with acute psychoses of varying type and origin. This medication was found to be effective. No significant side effects occurred.Several long-acting neuroleptics for injection are now available. The development of an oral compound of this type is an asset because of the manageability of the oral drug in the hands of family doctors and social psychiatrists.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Chlorpromazine; Clinical Trials as Topic; Delusions; Female; Hallucinations; Humans; Hydrocarbons, Halogenated; Male; Middle Aged; Paranoid Disorders; Piperidines; Psychomotor Disorders; Psychotic Disorders; Time Factors; Tranquilizing Agents

Topics: Adult; Aggression; Anticonvulsants; Anxiety; Carbamazepine; Clinical Trials as Topic; Diazepam; Dibenzazepines; Epilepsy; Frustration; Hallucinations; Humans; Intellectual Disability; Middle Aged; Nitriles; Object Attachment; Perceptual Disorders; Phenothiazines; Piperidines; Psychiatric Status Rating Scales; Psychopathology; Schizophrenia; Thiazines; Tranquilizing Agents

Swallowing difficulties (i.e., dysphagia) occur in up to 40% of the adult general population, particularly among the elderly prescribed solid oral dosage forms. Pimavanserin is approved for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis (PDP) as a 34-mg capsule formulation. Patients with PDP may be at-risk for dysphagia that could affect administration of intact pimavanserin capsules. The stability of oral pimavanserin was evaluated in different liquid/soft food vehicles.. The stability of pimavanserin intended for oral administration was assessed by sprinkling the contents of 1 pimavanserin 34-mg capsule into water (40 mL), applesauce (40 g), vanilla Ensure (60 mL), or non-pulp orange juice (60 mL).. The stability study demonstrated >95% recovery within 24 hours after contents of a 34-mg pimavanserin capsule were dispersed in applesauce, vanilla Ensure®, orange juice, or water. Assay values at 24 h for individual capsules were within 5% of time zero, and no significant change in the impurity profile was observed in any vehicle. Pimavanserin degradation products recovered from various food vehicles for individual and total degradation products were < 0.5% at all time points. In addition, the impurity profile of compatibility samples matched that obtained for a control sample.. These results support the ability of pimavanserin to be given orally by emptying the capsule contents into soft foods or liquids in accordance with the product label.

Topics: Adult; Aged; Hallucinations; Humans; Piperidines; Urea; Water

This was an open-label extension (OLE) study in patients previously completing a double-blind, placebo-controlled study or a previous OLE study. Safety was evaluated from adverse events (AEs), clinical laboratory results, motor symptoms, electrocardiograms (ECG), and mortality. Durability of response was assessed from the Clinical Global Impression-Severity (CGI-S) scale and Caregiver Burden Scale (CBS).. Of 459 participants treated in this OLE study (average age 71.2 years), the median duration of treatment was 454 days. Over the entire study period (approximately 11 years), ≥1 AE occurred in 392 (85.4%) patients; the majority were of mild to moderate intensity, with fall (32.0%), urinary tract infection (19.0%), and hallucination (13.7%) most common. Serious AEs occurred in 188 (41.0%) patients, and an AE leading to study termination or dose discontinuation occurred in 133 (29.0%) patients. Sixty-one patients died, 59 (12.9%) during treatment or within 30 days after the last dose of study drug; the observed mortality rate was 6.45 per 100 patient-years of exposure. Mean scores for the CGI-S scale and CBS generally remained stable for up to 192 weeks (>3.5 years).. Long-term treatment with pimavanserin 34 mg once daily demonstrated a favorable benefit/risk profile with no unexpected safety concerns. Mortality rates suggested no increased risk following long-term treatment.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Female; Hallucinations; Humans; Male; Middle Aged; Parkinson Disease; Piperidines; Psychotic Disorders; Urea

Clozapine was the widely accepted gold standard treatment for treatment resistant psychotic symptoms. Clozapine has efficacy of about 50% and some responding patients have to discontinue it due to serious adverse effects. The search for novel agents to use for clozapine-non-responders continues. One such possible agent is the non-dopaminergic antipsychotic pimavanserin, an inverse agonist of serotonin 5-HT2A receptors which was recently approved for the hallucinations and delusions of Parkinson's Disease Psychosis. We report here the successful results of using pimavanserin in patients with refractory hallucinations and delusions who failed to respond to clozapine. We also report similar results in refractory psychosis patients who did not receive clozapine.. We present ten cases of patients with schizophrenia and schizoaffective disorder with refractory hallucinations and delusions who received a trial of pimavanserin when clozapine or multiple antipsychotics failed. Six of ten patients had not responded to a clozapine trial. The subjects' ages ranged between 21 and 77 years and were followed up for several months.. All 10 patients with refractory hallucinations and delusions showed marked response to pimavanserin 34 mg/day within 4-8 weeks, with continuation of the response for several months of follow-up. Improvements in negative symptoms and social functioning were also observed in several patients.. This series of 10 cases of patients with refractory psychosis who responded to pimavanserin is an important new finding that has never been reported before. Controlled studies comparing clozapine and pimavanserin in refractory schizophrenia are warranted to confirm these clinical observations.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Delusions; Drug Resistance; Female; Hallucinations; Humans; Male; Middle Aged; Piperidines; Psychotic Disorders; Retrospective Studies; Schizophrenia; Serotonin 5-HT2 Receptor Antagonists; Urea; Young Adult

Topics: Antipsychotic Agents; Delusions; Drug Evaluation; Hallucinations; Humans; Parkinson Disease; Piperidines; United States; United States Food and Drug Administration; Urea

We report a 74-year-old female patient with Parkinson disease (PD). Around 2010, she developed depression and bradykinesia and was diagnosed as PD. In July 2014, she came to our hospital, of which she lived in the neighborhood. In the last part of December 2014, she felt uneasy about her fecal smell and saw a psychiatrist in the first part of January 2015. Quetiapine (25 mg/day) was added. In the last part of January, she complained of fecal smell everywhere and could not take a meal. No-one else could detect the smell. A diagnosis of olfactory hallucination was made. The next day after increasing to 75mg/day, however, she was admitted to our hospital because of refusing to take medicine. After introducing donepezil, olfactory hallucination subsided and her appetite was improved. Brain MRI showed atrophy of the bilateral temporal lobes and N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography (

Topics: Aged; Cerebrovascular Circulation; Donepezil; Female; Hallucinations; Humans; Indans; Iodine Radioisotopes; Iofetamine; Parkinson Disease; Piperidines; Radiopharmaceuticals; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Topics: Antiparkinson Agents; Delusions; Drug Approval; Drug Labeling; Hallucinations; Humans; Parkinson Disease; Piperidines; Urea

Donepezil and memantine are commonly prescribed antidementia drugs. There is a paucity of literature concerning pediatric ingestions of these drugs. We describe a case of a 2-year-old child who developed encephalopathy after an unintentional ingestion of donepezil and memantine. A 2-year-old girl was found by her family members agitated and reporting visual hallucinations. In the emergency department, she became sedated and had rightward eye deviation. She was hospitalized and had extensive neurological and infectious disease testing that was unremarkable, except for an electroencephalogram, which showed a nonspecific encephalopathy. She recovered with supportive care for 72 hours. Serum concentrations of donepezil and memantine measured on arrival were 470 ng/mL (therapeutic range, 25-50 ng/mL) and 32 ng/mL (therapeutic range, 70-150 ng/mL), respectively. This case demonstrates that unintentional ingestions of memantine and donepezil can potentially cause significant and prolonged neurological symptoms in pediatric patients.

Topics: Brain Diseases; Child, Preschool; Donepezil; Electroencephalography; Female; Hallucinations; Humans; Indans; Memantine; Piperidines

Topics: Acetylcholine; Cholinesterase Inhibitors; Donepezil; Drug Interactions; Hallucinations; Humans; Indans; Piperidines; Thalamus

Topics: Aged, 80 and over; Cholinesterase Inhibitors; Donepezil; Female; Hallucinations; Humans; Indans; Music; Piperidines; Presbycusis; Severity of Illness Index; Treatment Outcome; Widowhood

Topics: Adult; Antipsychotic Agents; Delusions; Dopamine Antagonists; Hallucinations; Humans; Male; Piperazines; Piperidines; Schizophrenia; Serotonin Antagonists; Treatment Outcome

Topics: Aged; Cholinesterase Inhibitors; Donepezil; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Indans; Lewy Body Disease; Piperidines

We discuss a case of a 67-year-old male with dementia with Lewy bodies (DLB) that was initially suspected as Creutzfeldt-Jakob disease (CJD) or another type of encephalopathy, because he showed rapidly progressive deterioration, myoclonus, gait disturbance and a decline in activities of daily living. The present study describes a clinically atypical case with probable DLB and reviews similar cases in the literature, and we propose a rapidly progressive clinical subtype of DLB.

Topics: Aged; Brain Ischemia; Cholinesterase Inhibitors; Creutzfeldt-Jakob Syndrome; Diagnosis, Differential; Donepezil; Hallucinations; Humans; Indans; Lewy Body Disease; Male; Mental Status Schedule; Neuropsychological Tests; Occipital Lobe; Parietal Lobe; Piperidines; Tomography, Emission-Computed, Single-Photon

Topics: Aged; Cholinesterase Inhibitors; Donepezil; Hallucinations; Humans; Indans; Male; Middle Aged; Music; Piperidines

We report the case of a patient who presented visual hallucinations and identification disorders associated with a Capgras syndrome. During the Capgras periods, there was not only a misidentification of his wife's face, but also a more global perceptive and emotional sexual identification disorder. Thus, he had sexual intercourse with his wife's "double" without having the slightest recollection feeling of familiarity towards his "wife" and even changed his sexual habits. To the best of our knowledge, he is the only neurological patient who made his wife a mistress. Starting from this global familiarity loss, we discuss the mechanism of Capgras delusion with reference to the role of the implicit system of face recognition. Such behavior of familiarity loss not only with face but also with all intimacy aspects argues for a specific disconnection between the ventral visual pathway of face identification and the limbic system involved in emotional and episodic memory contents.

Topics: Aged; Amnesia; Antipsychotic Agents; Atrophy; Brain; Capgras Syndrome; Donepezil; Hallucinations; Humans; Indans; Male; Memory; Movement Disorders; Neuropsychological Tests; Nootropic Agents; Parkinsonian Disorders; Piperidines; Recognition, Psychology; Risperidone; Sexual Behavior; Spouses; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Musical hallucinations (MH) typically occur among elderly individuals and are associated with hearing impairment. The authors describe a patient with features of typical MH who was successfully treated with donepezil, a cholinesterase inhibitor, as a combination therapy and who has not shown any subsequent cognitive decline for approximately 5 years. The efficacy of donepezil in this patient indicates that age-dependent dysfunction of cholinergic neurons might be related to the development of MH.

Topics: Aged, 80 and over; Donepezil; Drug Therapy, Combination; Female; Hallucinations; Hearing Disorders; Humans; Indans; Music; Nootropic Agents; Piperidines

Dementia with Lewy Bodies (DLB) is the second most common form of dementia in the elderly. Core features of the DLB are fluctuating cognitive symptoms, visual hallucinations and spontaneous parkinsonism. The clinical diagnostic criteria are very useful in the differentiation between DLB and Alzheimer's disease. The deficits in cholinergic neurotransmission are pronounced and associated with cognitive and psychotic symptoms. An 83 years old patient with DLB showed well formed recurrent visual hallucinations and fluctuating cognition and attention. There was no response to treatment with atypical neuroleptics. The patient responded within few days to treatment with Donepezil. Both cognitive and behavioural symptoms were improved significantly.

Topics: Aged; Cholinesterase Inhibitors; Donepezil; Hallucinations; Humans; Indans; Lewy Body Disease; Male; Mental Disorders; Piperidines; Treatment Outcome

The authors explored the neural substrate of visual hallucinations in dementia with Lewy bodies (DLB) by investigating changes in regional cerebral blood flow (rCBF) and psychiatric symptoms, before and after cholinesterase inhibitor treatment. Twenty subjects with DLB were treated with donepezil for a 12-week period. Hallucinations attenuated while receiving therapy, whereas occipital rCBF focally increased, suggesting that functional visual association cortex deficits may cause visual hallucinations in patients with DLB.

Topics: Aged; Aged, 80 and over; Cerebrovascular Circulation; Donepezil; Female; Hallucinations; Humans; Indans; Lewy Body Disease; Male; Occipital Lobe; Piperidines; Regional Blood Flow; Tomography, Emission-Computed, Single-Photon

Fluctuations in consciousness and visual hallucinations are common neuropsychiatric features of dementia with Lewy bodies and Parkinson's disease dementia. To investigate potential neural correlates, we compared how changes in brain perfusion over a 1-year period were related to changes in the severity of these key clinical features. We recruited 29 subjects with either Parkinson's disease with dementia (15 subjects) or dementia with Lewy bodies (14 subjects). Cerebral perfusion was measured using HMPAO SPECT at baseline, and repeated 1 year later. The presence of hallucinations (Neuropsychiatric Inventory), severity of fluctuations in consciousness (fluctuation assessment scale) and cognitive ability (CAMCOG) were assessed at both time points. After controlling for changes in cognitive ability and effect of cholinesterase medication, we found a significant correlation between an increase in perfusion in midline posterior cingulate and decrease in hallucination severity. There was also a significant correlation between increased fluctuations of consciousness and increased thalamic and decreased inferior occipital perfusion. We have identified important neural correlates of key clinical features in Lewy body dementia and postulate that the associations can be understood through the influence of the cholinergic system on attention.

Topics: Aged; Cholinesterase Inhibitors; Consciousness Disorders; Donepezil; Female; Hallucinations; Hemodynamics; Humans; Indans; Lewy Body Disease; Male; Neuropsychological Tests; Oximes; Piperidines; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

To describe the assessment and treatment of an elderly woman with parkinsonism, progressive memory and cognitive deficits, and visual hallucinations.. The patient presented with a 10-year history of hand tremors, an 8-year history of short-term memory problems, and a 3-4-year history of visual hallucinations. Treatment with donepezil and rivastigmine (successively) did not produce the desired benefits. Then she was started on galantamine 4 mg b.i.d. (escalated to 8 mg b.i.d.).. The patient's social interaction improved and cognitive decline appeared to be stabilized; hallucinations and agitation were also better controlled.. By current criteria, this subject would be labeled as having Parkinson's disease with dementia, although she exhibited the core features of dementia with Lewy body disease. As suggested in previous studies, cholinesterase inhibitors may be effective in treating psychotic symptoms; however, all currently available agents may not be equally effective.

Topics: Aged; Aged, 80 and over; Carbamates; Cognition Disorders; Donepezil; Drug Resistance; Female; Galantamine; Hallucinations; Humans; Indans; Lewy Body Disease; Neuroprotective Agents; Nootropic Agents; Phenylcarbamates; Piperidines; Psychomotor Agitation; Rivastigmine; Social Behavior

Charles Bonnet syndrome (CBS) is characterized by the presence of complex visual hallucinations in psychologically normal people. Although visual hallucinations in the elderly are often associated with dementia with Lewy body (DLB), Alzheimer's disease and delirium, they are excluded from the diagnosis of typical CBS, as are cognitive or psychiatric disturbances, sleep disorders and focal neurological lesions. Here, we describe a patient with typical CBS, who responded to donepezil, a cholinesterase inhibitor, and has not shown any symptoms suggestive of Alzheimer's disease or DLB for approximately the past 40 months. However, follow-up examination of her clinical symptoms is necessary for a definite exclusion of Alzheimer's disease and DLB. The effectiveness of donepezil indicates that the patient's visual hallucinations might be related to dysfunction of cholinergic neurones, although she did not exhibit any cognitive decline, or morphological and physiological brain pathology. Because donepezil has fewer adverse effects than anticonvulsants and neuroleptic drugs, it may be a safer option for the treatment of CBS in the elderly.

Topics: Aged; Cholinesterase Inhibitors; Diagnosis, Differential; Donepezil; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Indans; Piperidines; Vision Disorders

We report a 75-year-old Japanese woman with probable dementia with Lewy bodies (DLB). At the age of 64, she showed left hand resting tremor, and gradually developed bradykinesia, and rigidity. She was diagnosed as having parkinsonism and took medication. At the age of 70, she showed hallucination and dementia. As she had developing cognitive dysfunction and hallucination and parkinsonism, she was diagnosed to have probable DLB. At the age of 75, after administration of donepezil, she showed severe psychosis and worsened parkinsonism, and was admitted to hospital. On neurological examination, she showed severe rigidity and akinesia, and behavioral immobility like "waxy flexibility" or motiveless resistance to maintenance of rigid posture against attempts to be moved. The phenomena, she presented as motor abnormalities, were thought to be catatonia. In consideration of clinical course, her catatonia and worsened parkinsonism was thought to be induced by donepezil and she was stopped the administration of donepezil. After treatment with trihexiphenizil, she had improvement of motor abnormalities and worsened parkinsonism. It is important to recognize that donepezil may induce catatonia on the patients of parkinsonism with severe dementia.

Topics: Aged; Catatonia; Donepezil; Female; Hallucinations; Humans; Indans; Lewy Body Disease; Nootropic Agents; Parkinsonian Disorders; Piperidines

Visual hallucinations (VHs) are common psychiatric symptoms in patients with long-standing Parkinson's disease (PD). Treatment with neuroleptics or withdrawal of anti-PD drugs may improve VHs but will worsen motor dysfunctions. The authors report on 3 patients with long-standing PD who were treated with the cholinesterase inhibitor donepezil for the treatment of VHs. Each received a daily dose of 5 mg of donepezil, after reducing or discontinuing anti-PD medications had failed to relieve the VHs. In 2 patients (patient 1, 2), donepezil decreased VHs without worsening motor dysfunctions. In addition, the cognitive status of patient 2 improved. In patient 3, donepezil also resolved VHs, but delusions developed during treatment. After discontinuing donepezil, delusions disappeared and VHs reappeared. Donepezil may ameliorate visual hallucinations in PD patients, but controlled, double-blind trials are necessary to further clarify the effect of this drug on VHs in PD.

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Cognition Disorders; Donepezil; Female; Hallucinations; Humans; Indans; Male; Middle Aged; Parkinson Disease; Piperidines; Psychomotor Disorders; Severity of Illness Index

Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Cognition; Dementia; Donepezil; Female; Hallucinations; Humans; Indans; Male; Mental Status Schedule; Piperidines; Treatment Outcome

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

The patient was a 68-year-old man with a 1-year history of delusions related to well-formed and detailed visual hallucinations. Bromperidol 12 mg was prescribed to treat his symptoms. After a diagnosis of dementia of Alzheimer's type was suspected, the patient received donepezil hydrochloride 5 mg. One week later, the patient's Parkinsonism deteriorated. One month later, the patient developed radical edema of the eyelids and the anterior neck, hypoproteinemia, and severe anteflexion of the body. One and a half months later, the patient developed malignant syndrome. His medication was discontinued and parenteral nutrition was started. The patient recovered from his malignant syndrome. However, 1 month later, his Parkinsonism had not improved. The patient received levodopa to treat his Parkinsonism and his symptoms subsequently improved. The hallucinations and systematized delusions returned. The patient's cognitive impairment deteriorated on one side. The aggravation of extrapyramidal symptoms and the development of malignant syndrome were believed to have been caused by the combination of bromperidol and donepezil hydrochloride and poor nutrition. Caution should be exercised when prescribing an antipsychotic drugs with donepezil hydrochloride.

Topics: Aged; Donepezil; Drug Therapy, Combination; Hallucinations; Haloperidol; Humans; Indans; Lewy Body Disease; Male; Neuroleptic Malignant Syndrome; Nootropic Agents; Piperidines

Topics: Aged; Diagnosis, Differential; Donepezil; Female; Hallucinations; Humans; Indans; Lewy Body Disease; Nootropic Agents; Piperidines; Syndrome; Vision Disorders

A case of hypnopompic hallucinations associated with donepezil is described. Electroencephalogram (EEG) and sleep EEG changes are common in Alzheimers Disease and acetylcholinesterase inhibitor drugs can affect rapid eye movement sleep and alertness. The importance of assessing sleep in patients treated with these drugs is discussed.

Topics: Alzheimer Disease; Animals; Cholinesterase Inhibitors; Cognition Disorders; Diagnosis, Differential; Donepezil; Electroencephalography; Hallucinations; Humans; Indans; Insecta; Male; Middle Aged; Personality; Piperidines; Sleep, REM

Topics: Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Hallucinations; Humans; Indans; Parkinson Disease; Piperidines; Treatment Outcome

Topics: Age Factors; Aged; Cholinesterase Inhibitors; Dementia; Donepezil; Hallucinations; Humans; Indans; Male; Piperidines; Visual Perception

The atypical antipsychotic drug olanzapine has been proposed for treatment of dopaminergic psychosis in Parkinson's disease (PD). We report on a 68-year-old patient who developed a severe akinetic-rigid extrapyramidal syndrome, accompanied by additional paranoid symptoms, following olanzapine treatment of optic hallucinosis in PD. Olanzapine may also induce clinically relevant extrapyramidal side effects in PD patients.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Drug Therapy, Combination; Hallucinations; Humans; Levodopa; Male; Olanzapine; Paranoid Disorders; Parkinson Disease; Piperidines; Pirenzepine; Selegiline; Severity of Illness Index

Topics: Aged; Antipsychotic Agents; Dementia; Evoked Potentials, Visual; Hallucinations; Humans; Isoxazoles; Magnetic Resonance Imaging; Male; Piperidines; Risperidone; Visual Cortex

Topics: Aged; Antipsychotic Agents; Hallucinations; Humans; Isoxazoles; Levodopa; Parkinson Disease; Piperidines; Risperidone

Topics: Biperiden; Hallucinations; Humans; Piperidines; Trihexyphenidyl

Topics: Analgesics; Depressive Disorder, Major; Female; Hallucinations; Humans; Methadone; Middle Aged; Piperidines

The author calls attention to mood-elevation as a side effect of Biperiden HCL and Trihexyphenidyl HCL, two anticholinergic antiparkinsonian agents. This is of significance because of the despondency and anergy often seen in schizophrenics taking antipsychotic medication and because of the difficulty discerning the origin of affective changes in the face of polypharmacy.

Topics: Adolescent; Adult; Antiparkinson Agents; Basal Ganglia Diseases; Biperiden; Emotions; Euphoria; Female; Hallucinations; Humans; Male; Middle Aged; Piperidines; Schizophrenia; Trihexyphenidyl

Topics: Alcoholism; Antipsychotic Agents; Chronic Disease; Delayed-Action Preparations; Female; Fluphenazine; Hallucinations; Humans; Male; Palmitic Acids; Paranoid Disorders; Piperidines; Psychotic Disorders; Schizophrenia; Sulfonamides

Topics: Adult; Chronic Disease; Female; Hallucinations; Humans; Hydrocarbons, Halogenated; Male; Motor Skills; Paranoid Disorders; Piperidines; Psychiatric Status Rating Scales; Schizophrenia; Spiro Compounds; Thinking; Tranquilizing Agents

Topics: Alcoholic Intoxication; Aluminum; Aminopyrine; Anti-Inflammatory Agents; Ascorbic Acid; Benzyl Compounds; Child; Child, Preschool; Cosmetics; Female; Hallucinations; Humans; Hyperkinesis; Male; Methylamines; Nalidixic Acid; Perfume; Phenethylamines; Piperidines; Poisoning; Pyrazoles; Rutin; Shock; Speech Disorders

Topics: Anxiety; Benzimidazoles; Chronic Disease; Hallucinations; Humans; Ketones; Mental Disorders; Piperidines; Psychotic Disorders; Schizophrenia; Schizophrenia, Disorganized; Tranquilizing Agents

Topics: Adult; Child; Child, Preschool; Delirium; Exanthema; Female; Gels; Hallucinations; Histamine H1 Antagonists; Humans; Hypersensitivity; Male; Ointments; Piperidines; Psychoses, Substance-Induced

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Autistic Disorder; Autonomic Nervous System; Catatonia; Female; Hallucinations; Humans; Hypnotics and Sedatives; Liver Function Tests; Male; Mental Disorders; Nausea; Neurotic Disorders; Paranoid Disorders; Personality Disorders; Phenothiazines; Piperidines; Schizophrenia; Sleep Wake Disorders; Stimulation, Chemical; Sweating; Tremor; Vascular Diseases; Vomiting

Topics: Adult; Aged; Female; Hallucinations; Humans; Male; Middle Aged; Piperidines

Topics: Alcohols; Antiemetics; Hallucinations; Humans; Piperidines

Topics: Adult; Aged; Hallucinations; Humans; Male; Mental Disorders; Middle Aged; Paranoid Disorders; Piperidines; Psychotic Disorders; Schizophrenia

Topics: Hallucinations; Humans; Piperidines

Topics: Aged; Analgesics; Female; Hallucinations; Humans; Male; Middle Aged; Nitriles; Pain; Phenothiazines; Piperidines; Tranquilizing Agents

Topics: Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus; Glucose Tolerance Test; Hallucinations; Hospitals, Psychiatric; Inpatients; Mental Disorders; Piperidines; Placebos; Schizophrenia; Toxicology

Topics: Bipolar Disorder; Butyrophenones; Hallucinations; Humans; Hypnotics and Sedatives; Intellectual Disability; Mental Disorders; Paranoid Disorders; Paresis; Parkinsonian Disorders; Piperidines; Psychomotor Agitation; Psychotic Disorders; Schizophrenia

Topics: Bridged-Ring Compounds; Bromine; Hallucinations; Humans; Hypnotics and Sedatives; Paranoid Disorders; Piperidines; Substance-Related Disorders; Urea

Topics: Drug Combinations; Glycolates; Hallucinations; Humans; Mental Disorders; Mentally Ill Persons; Piperidines; Pyrrolidines

Topics: Convulsive Therapy; Electricity; Electroconvulsive Therapy; Electroshock; Hallucinations; Humans; Piperidines; Psychopharmacology

Topics: Chronic Disease; Hallucinations; Humans; Mental Disorders; Piperidines; Psychopharmacology; Syndrome

Topics: Hallucinations; Humans; Piperidines; Schizophrenia

Topics: Confusion; Delusions; Hallucinations; Humans; Piperidines

Topics: Delusions; Hallucinations; Humans; Piperidines

Topics: Delusions; Electroconvulsive Therapy; Hallucinations; Humans; Piperidines; Psychosurgery; Psychotherapy; Psychotic Disorders

Topics: Delusions; Electroconvulsive Therapy; Hallucinations; Humans; Piperidines; Psychosurgery; Psychotherapy; Psychotic Disorders

Topics: Bridged-Ring Compounds; Hallucinations; Humans; Mental Disorders; Piperidines; Psychotic Disorders; Syndrome; Urea

Topics: Hallucinations; Humans; Piperidines; Syndrome