clozapine and Lewy-Body-Disease

Psychosis may be seen with several movement disorders. As pharmacological treatments can sometimes worsen movement disorders, psychosis in these situations can be complex for clinicians to manage. This review covers the management of psychosis in three different movement disorders: Parkinson's disease, dementia with Lewy bodies and Huntington's disease.

Topics: Antipsychotic Agents; Clozapine; Haloperidol; Humans; Huntington Disease; Lewy Body Disease; Parkinson Disease; Patient Education as Topic; Psychotic Disorders; Risperidone

Lewy body dementia and Parkinson disease dementia are frequent causes of degenerative dementia: 20% of the dementias in patients older than 65 years are caused by the former and nearly 80% of patients with advanced Parkinson disease develop the latter. Symptoms of Lewy body dementia include fluctuations of cognitive performance, frontal and visuospatial impairment, visual hallucinations, and parkinsonism. Parkinson disease dementia could be differentiated in two subtypes: a "subcortical" subtype, characterized by frontal impairment with apathy and dullness and a "cortical" subtype with symptoms similar to those of Lewy body dementia. Mastery of potential iatrogenic factors is important: psychotropic drugs must be prescribed at the strict minimum, and L-dopa monotherapy at the minimal dose acceptable for correcting Parkinsonian motor symptoms should be the rule. Acetylcholinesterase inhibitors may be useful in both these types of dementia: rivastigmine is approved for treating Parkinson disease dementia and clozapine for reducing hallucinations.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Dementia; Diagnosis, Differential; Disease Progression; Dopamine Agents; Humans; Iatrogenic Disease; Levodopa; Lewy Body Disease; Neuroprotective Agents; Nootropic Agents; Parkinson Disease; Parkinsonian Disorders; Phenylcarbamates; Psychotropic Drugs; Rivastigmine; Serotonin Antagonists

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

Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders.. A comprehensive literature review.. Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer's disease.. There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

Topics: Aged; Alzheimer Disease; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder; Drug Administration Schedule; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Risperidone

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

Dementia with Lewy bodies (DLB) is characterized by neurocognitive disorders associated with core clinical features including hallucinations. There is currently no cure but a combination of symptomatic treatments: clozapine is commonly used in DLB-related psychosis. Pimavanserin is a serotonin 5HT-2A receptor inverse agonist that has recently been shown to reduce psychosis related to dementia. Trazodone is a serotonin reuptake inhibitor and a 5-HT2 receptor antagonist: it is effective in the treatment of the frontal syndrome and is commonly used in frontotemporal degeneration.. We describe three patients with DLB, hospitalized in the cognitive-behavioral unit of the University Hospitals of Strasbourg, who presented with major visual hallucinations, delusion, and an orbitofrontal syndrome including disinhibition, agitation, and irritability. The 3 patients were intolerant of low-dose Clozapine (neutropenia for one, somnolence for the other and Pisa syndrome and falls for the last one). We evaluated the Neuropsychiatric Inventory (NPI) before and after the introduction of both treatments.. Given their psychotic and frontal symptoms, we used Pimavanserin and Trazodone simultaneously. After 4 to 6 weeks of treatment, a marked improvement was observed in all 3 patients, with a decrease of the NPI scores from a mean of 88 to 38.. To our knowledge, there is no previously described combination of these two treatments in DLB. A clinical trial combining these two molecules against pervasive behavioral disorders in DLB would be interesting in view of these preliminary results.

Topics: Clozapine; Dementia; Drug Inverse Agonism; Hallucinations; Humans; Lewy Body Disease; Trazodone

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

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

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia associated with poor prognosis and high carers' burden. Neuropsychiatric symptoms worsen this prognosis and are a high source of distress for service users and their carers. However, there is currently insufficient evidence to support the pharmacological and non-pharmacological management of these symptoms. Acetylcholinesterase inhibitors are the first-line pharmacological option, but challenging risky behaviours may persist despite their use. Antipsychotic medications are indicated in such clinical scenarios, but there is very limited evidence to support the efficacy and safety of these medications for managing neuropsychiatric symptoms in DLB. Hence, we report an individual with DLB with severe distressing persistent visual hallucinations and agitation. After multiple treatment options had failed, clozapine was successfully initiated with substantial improvement in both clinical and functional outcomes. Further studies are warranted for evaluating the efficacy of clozapine in managing neuropsychiatric symptoms in DLB.

Topics: Aged; Antipsychotic Agents; Clozapine; Hallucinations; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Male; Treatment Outcome

Visual hallucinations (VH) are sometimes difficult to treat in patients with Lewy body dementia (LBD). We describe the concurrent use of clozapine and levodopa for the treatment of persistent VH and parkinsonism in a patient with LBD and severely increased sensitivity to antipsychotics.

Topics: Aged; Antipsychotic Agents; Brain; Clozapine; Comorbidity; Hallucinations; Humans; Levodopa; Lewy Body Disease; Male; Parkinson Disease; Treatment Outcome

Topics: Antiparkinson Agents; Clozapine; Delusions; Drug Therapy, Combination; Humans; Levodopa; Lewy Body Disease; Movement Disorders; Neuroleptic Malignant Syndrome; Severity of Illness Index

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

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