olanzapine and Lewy-Body-Disease

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

The association between Down's syndrome (DS) and Alzheimer's disease is well established. This paper presents a review of the literature, suggesting a possible association between DS and the more recently recognised dementia with Lewy bodies (DLB). Patients with DLB frequently present with changes in affect and behaviour, and in particular with psychotic symptoms. The literature suggests a possible role for atypical neuroleptics in the management of psychosis in DLB.

Topics: Adolescent; Adult; Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Comorbidity; Depressive Disorder; Down Syndrome; Humans; Lewy Body Disease; Middle Aged; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors

This study sought to determine whether patients with dementia with Lewy bodies (DLB) and psychosis responded to treatment with olanzapine.. This was a post hoc analysis of a subgroup of patients with DLB included in a larger double-blind, placebo-controlled, randomized parallel group trial of olanzapine for the treatment of psychosis in patients with Alzheimer's disease. Patients meeting the consensus criteria for DLB and exhibiting parkinsonism and visual hallucinations were selected from the initial study. Psychosis was assessed with the Neuropsychiatric Inventory/Nursing Home (NPI-NH) version and the Brief Psychiatric Rating Scale (BPRS). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale.. Twenty-nine patients met the criteria for DLB; 10 were randomized to placebo, 5 received 5 mg of olanzapine, 7 received 10 mg of olanzapine and 7 received 15 mg of olanzapine. Patients with DLB treated with 5 mg of olanzapine showed significant reductions in delusions and hallucinations. Patients treated with 10 mg showed a significant reduction in the NPI-NH delusion subscale score. No significant differences were found between the 15-mg group and the placebo group. Confirmatory findings emerged from an analysis of the BPRS. Caregivers reported decreased disruptions in their occupational routines for the group receiving 5 or 10 mg of olanzapine. There was no significant exacerbation of parkinsonian symptoms in any study group, no decrement in Mini-Mental State Examination scores in any of the treatment groups, and symptoms suggestive of anticholinergic toxicity did not differ among treatment groups.. This preliminary analysis suggests that olanzapine (5 or 10 mg) reduces psychosis in patients with DLB without worsening parkinsonism.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Behavior; Benzodiazepines; Cognition; Delusions; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hallucinations; Humans; Lewy Body Disease; Male; Olanzapine; Parkinsonian Disorders; Personality Inventory; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders

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

We report the patient of a 53-year-old woman who developed subacute-onset marked tonge protrusion and bite. She was diagnosed as dementia with Lewy bodies (DLB) from the clinical features including progressive cognitive decline, visual hallucinations, parkinsonism, and severe insomnia and depression, and the radiological finding of low dopamine transported uptake in basal ganglia by Dat SCAN and low blood circulation in occipital lobe of cerebrum. The patient received 600 mg doses of levodopa for over a year, followed by rotigotine and ropinirole with a rapid increase of dosage. It is believed that these treatments stimulated and sensitized dopamine D1 receptors, thereby inducing lingual dystonia. Furthermore, the patient demonstrated dyspnea and attacks of apnea caused by the closure of bilateral vocal cords due to laryngeal dyskinesia. After initiation of the neuroleptic, olanzapine, for a short duration, the high dose of levodopa overlapped with neuroleptic sensitivity, suggesting DOPA-induced dystonia and dyskinesia. This interaction can sometimes lead to lethal adverse events, and must be considered very important when treating patients with DLB.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bites and Stings; Drug Interactions; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Indoles; Laryngeal Diseases; Levodopa; Lewy Body Disease; Middle Aged; Olanzapine; Receptors, Dopamine D1; Tetrahydronaphthalenes; Thiophenes; Tongue Diseases

Many patients with Lewy body dementia develop visual hallucinations and other psychiatric symptoms. These patients are hypersensitive to antipsychotic drugs. Although patients tolerate atypical better than typical antipsychotics, both types can cause major extrapyramidal side effects. The anticonvulsant mood stabilizer topiramate, which does not cause parkinsonism, has been used as adjuvant therapy for both the positive and negative symptoms of schizophrenia; these symptoms can resemble those of Lewy body dementia. This report documents a 65-year-old woman with a 3-year history of progressive dementia that over the past 2 years had become complicated by severe extrapyramidal symptoms and agitated hallucinations. Her hallucinations became daily and were disrupting to her family. She was given a clinical diagnosis of Lewy body dementia after imaging and laboratory studies ruled out other etiologies. Treatment with olanzapine relieved her psychotic symptoms but caused severe dystonias, daily myoclonic jerks, and tremors. Stopping the olanzapine and starting topiramate 25 mg daily eliminated the hallucinations and agitation without worsening her extrapyramidal side effects. However, the topiramate was stopped because the patient reportedly developed anorexia and significant weight loss. Her hallucinations returned. When topiramate was reinstated at 12.5 mg a day, her agitation resolved, although her hallucinations continued. After 6 months on this dose, her agitation was still fairly well controlled without serious side effects or worsening of her parkinsonian symptoms.

Topics: Aged; Anticonvulsants; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Fructose; Hallucinations; Humans; Lewy Body Disease; Neuroprotective Agents; Olanzapine; Psychomotor Agitation; Schizophrenia; Topiramate; Treatment Outcome

Topics: Benzodiazepines; Female; Humans; Lewy Body Disease; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine

We present a 72-year-oldpatient with probable diffuse Lewy body disease and visual hallucinations, who developed subacute reversible "dropped head syndrome" and parkinsonian signs after the introduction of olanzapine at a total daily dose of 10 mg. One week after olanzapine was withdrawn, the patient's posture started to improve. Further improvement was achieved after dopaminergic substitution. Clinical and electrophysiological observations might indicate neck extensor myopathy due to axial rigidity or focal neck dystonia, induced by dopamine receptor blockade.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dopamine Antagonists; Female; Hallucinations; Head Movements; Humans; Kyphosis; Lewy Body Disease; Muscular Diseases; Olanzapine

In two patients, men aged 80 and 75 years with cognitive deterioration, hallucinations and parkinsonism, the clinical diagnosis 'dementia with Lewy bodies' was established. Treatment with an atypical antipsychotic, risperidone and olanzapine respectively, resulted in an exacerbation of the parkinsonism. Rivastigmine evidently improved the psychosis, the anxiety and the cognitive, mood and behaviour disorders. Titrated treatment with levodopa improved the mobility without an increase of the psychosis. The treatment of dementia with Lewy bodies is complex. Levodopa can lead to an increase in visual hallucinations. Antipsychotics often cause serious side effects, such as increasing parkinsonism, sedation and cognitive deterioration. Cholinesterase inhibitors such as rivastigmine could possibly provide an alternative treatment for the neuropsychiatric symptoms.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Carbamates; Cholinesterase Inhibitors; Drug Therapy, Combination; Humans; Levodopa; Lewy Body Disease; Male; Neuroprotective Agents; Olanzapine; Phenylcarbamates; Pirenzepine; Risperidone; Rivastigmine; Treatment Outcome

Topics: Aged; Benzodiazepines; Female; Humans; Lewy Body Disease; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors