Antipsychotics for Lewy Body Disease
(CAMELOT Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: The University of Texas Health Science Center at San Antonio
Must be taking: Antipsychotics
Must not be taking: Antipsychotics
Disqualifiers: Caregiver unavailable, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
The primary objective of this study is to determine whether treatment with pimavanserin or quetiapine is associated with a greater improvement in psychosis when used in a routine clinical setting to treat hallucinations and/or delusions due to Parkinson's disease (PD) or dementia with Lewy bodies (DLB) - collectively referred to as Lewy body disease (LBD).
Will I have to stop taking my current medications?
If you are currently taking an antipsychotic medication, you will need to stop before joining this trial.
What evidence supports the effectiveness of the drug Pimavanserin for treating psychosis in Lewy Body Disease?
Is it safe to use antipsychotics like Pimavanserin and Quetiapine for Lewy Body Disease?
Pimavanserin and Quetiapine are considered safer options for treating psychosis in Lewy Body Disease compared to other antipsychotics, as they are less likely to worsen motor symptoms or cause serious side effects like neuroleptic sensitivity. Pimavanserin is FDA-approved for Parkinson's disease psychosis and has shown potential in Lewy Body Disease, while Quetiapine is noted for reducing psychiatric symptoms without increasing the risk of neuroleptic sensitivity.14567
How is the drug Pimavanserin unique in treating Lewy Body Disease?
Pimavanserin is unique because it treats psychosis in Lewy Body Disease without worsening motor symptoms, unlike many other antipsychotics that can cause severe side effects in these patients. It works by targeting serotonin receptors instead of dopamine, making it a safer option for those with neuroleptic sensitivity.14589
Eligibility Criteria
This trial is for individuals with hallucinations or delusions due to Parkinson's disease (PD) or dementia with Lewy bodies (DLB), who need to start antipsychotic treatment. Participants must be seen at the UT Health San Antonio neurology clinic and have a doctor willing to manage both Pimavanserin and Quetiapine treatments.Inclusion Criteria
Clinical equipoise between quetiapine and pimavanserin must exist
My doctor is experienced in prescribing and managing quetiapine and pimavanserin.
Patients seen in the neurology clinic at UT Health San Antonio
See 2 more
Exclusion Criteria
Caregiver unavailable to complete NPI-Q
I cannot take certain medications due to health risks.
My doctor is not willing to manage my medication.
See 1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants are randomized to receive either quetiapine or pimavanserin to treat psychosis in Lewy body disease
6 months
Regular visits as per clinical practice
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Pimavanserin (Atypical Antipsychotic)
- Quetiapine (Atypical Antipsychotic)
Trial OverviewThe study aims to compare the effectiveness of two antipsychotic medications, Pimavanserin and Quetiapine, in improving psychosis symptoms in patients with Lewy body disease over time when used in routine clinical practice.
Participant Groups
2Treatment groups
Active Control
Group I: pimavanserinActive Control1 Intervention
Elderly patients with dementia-related psychosis will be treated with pimavanserin, an atypical antipsychotic indicated for treatment of hallucinations and delusions associated with Parkinson's disease.
Group II: quetiapineActive Control1 Intervention
Elderly patients with dementia-related psychosis will be treated with quetiapine, an atypical antipsychotic indicated for the treeatment of: schizophrenia, bipolar I manic episodes and bipolar depressive episodes.
Pimavanserin is already approved in United States for the following indications:
🇺🇸 Approved in United States as Nuplazid for:
- Hallucinations and delusions associated with Parkinson's disease psychosis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Health SystemSan Antonio, TX
UT Health Science Center - San AntonioSan Antonio, TX
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Who Is Running the Clinical Trial?
The University of Texas Health Science Center at San AntonioLead Sponsor
Alzheimer's AssociationCollaborator
References
Pimavanserin Use in Lewy Body Dementia: A Case Report Demonstrating the Medication's Efficacy. [2023]Pimavanserin is an antipsychotic that is approved for use in Parkinson's disease psychosis. Working as a serotonin 2A inverse agonist, pimavanserin allows patients to improve their psychotic symptoms without worsening the motor symptoms of Parkinson's. This mechanism is mediated via serotonin receptors and may allow for pimavanserin to be considered for use in other disease processes that present with psychosis. Here, the authors describe the case of a 75-year-old man with Lewy Body Dementia (LBD) who was started on pimavanserin. The response of the patient to the medication was measured over a six-week time course using the Scales for the Assessment of Positive Symptoms of Schizophrenia (SAPS). Overall, pimavanserin was shown to be effective in this patient with LBD. The authors also provide a review of the sparse literature attesting to other off-label uses for this unique antipsychotic.
Quetiapine treatment of psychotic symptoms and aggressive behavior in patients with dementia with Lewy bodies: a case series. [2022]The authors describe here the clinical outcomes of quetiapine treatment in nine patients with dementia with Lewy bodies (DLB) who manifested psychotic symptoms and aggressive behavior. Patients who had a score of 3 or higher on any of the three items of the Neuropsychiatric Inventory (NPI), agitation/aggression, hallucinations, and delusions, were given quetiapine 25-75 mg/day. Each patient's clinical status was assessed at baseline and after 4 and 8 weeks of treatment by using the NPI, Mini-Mental State Examination (MMSE), and Simpson-Angus Scale (S-A). Five of nine patients had a positive response with a decline of more than 50% in the sum of scores for three items of the NPI. The other three patients withdrew from quetiapine treatment due to somnolence or orthostatic hypotension. The remaining patient exhibited no clinically significant change in the NPI score. The S-A scale was not affected by quetiapine treatment in any patient. These findings suggest that quetiapine may be effective in treating psychotic symptoms and disruptive behavior in some patients with DLB. Further placebo-controlled, randomized, double-blind trials with this drug are needed to confirm this observation.
Treatment of psychosis in Parkinson's disease and dementia with Lewy Bodies: A review. [2021]There is a considerable overlap between Parkinson's Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB). They present a challenge therapeutically, with regard to morbidity and mortality risk. In particular, symptoms of psychosis in these conditions augur a considerably increased burden. To date, there has been a myriad of prospective, retrospective and case studies examining the use of neuroleptics in the treatment of psychotic symptoms in PDD/DLB. Clozapine has the most robust evidence base however its use is limited by agranulocytosis risk and the associated need for frequent blood count monitoring. Quetiapine is more readily used, however, it has a more equivocal evidence base, in terms of efficacy. Other neuroleptics have thus far demonstrated mixed results with increased risk of extrapyramidal worsening. In addition to the atypical agents, the introduction of pimavanserin has provided another treatment option for Parkinson's Disease Psychosis (PDP), decreasing concern for deterioration in motor function. We await further research to confidently demonstrate its efficacy and safety in DLB psychosis. Cholinesterase inhibitors likely have a limited role in treating milder psychosis symptomatology in DLB and perhaps PDD. After review of the current literature for antipsychotic therapy in both PDD and DLB, we provide a logical framework for addressing psychotic symptoms in each condition.
Neuroleptic Sensitivity in Dementia with Lewy Body and Use of Pimavanserin in an Inpatient Setting: A Case Report. [2022]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.
Lewy body dementia: the litmus test for neuroleptic sensitivity and extrapyramidal symptoms. [2018]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.
[Medication review for dementia patients]. [2012]Due to demographic changes we are faced with several challenges as an increasing prevalence of dementia patients. We report on a medication review of a patient with Alzheimer's disease as well as Lewy body dementia. The intake of risperidone was interrupted instead of a dose reduction which was recommended by the psychiatrist to improve mobility. As an adverse event the patient developed serious psychiatric symptoms which were treated in an acute care facility. We discussed several alternative treatment options (pipamperon, melperon, haloperidol, risperidone, clozapine, olanzapine, aripiprazol, and quetiapin) in a case conference. Due to a short half life period and insignificant anticholinergic effects we decided to choose quetiapin. Despite a small number of taken drugs we identified several potential drug related problems which were solved in a multipartite health care professional team.
Patients treated with pimavanserin or quetiapine for Parkinson's disease psychosis: analysis of health resource utilization patterns among Medicare beneficiaries. [2023]Pimavanserin (PIM) is the only FDA approved atypical antipsychotic (AAP) for the treatment of Parkinson's Disease Psychosis (PDP) while other off-label AAPs like quetiapine (QUE) are also used. Real-world comparative effects of PIM and QUE on health resource utilization (HCRU) may provide insights about their relative benefits.
Pimavanserin Treatment for Psychosis in Patients with Dementia with Lewy Bodies: A Case Series. [2023]BACKGROUND Many patients with dementia with Lewy bodies (DLB) experience cholinesterase inhibitor- and antipsychotic-resistant psychosis. The new second-generation antipsychotic pimavanserin has been used with some success in the treatment of psychosis in other forms of dementia, including Alzheimer disease and Parkinson disease dementia. It is possible that pimavanserin may also be useful in the treatment of psychosis in DLB. We sought to describe the disease course and treatment of psychosis in 4 patients with DLB who were prescribed pimavanserin after other medications failed to reduce the frequency or severity of hallucinations and delusions. CASE REPORT This is a case series of 4 male patients (ages 56 to 74 at the beginning of the reports) who developed DLB and psychosis (eg, visual illusions, visual and olfactory hallucinations, and paranoid delusions). All 4 patients were prescribed cholinesterase inhibitors (eg, donepezil or rivastigmine) prior to pimavanserin, and only 1 patient experienced improved psychosis while on cholinesterase inhibitors. All 3 patients who were prescribed first-generation antipsychotics (eg, haloperidol) or traditional second-generation antipsychotics (eg, olanzapine, risperidone, or quetiapine) experienced initial or lasting side effects with no improvement of psychosis. Conversely, all 4 patients tolerated pimavanserin well, and 3 of the 4 patients experienced significant improvement of psychosis (eg, fewer hallucinations, fewer delusions, reduced paranoia, and/or reduced distress or agitation related to hallucinations and delusions) when prescribed pimavanserin. CONCLUSIONS This case series suggests that pimavanserin is tolerable in older males with DLB and that it may be useful for the reduction of distressful hallucinations, delusions, and paranoia in patients with DLB.
Clozapine use in diffuse Lewy body disease. [2013]Diffuse Lewy body disease, a severely disabling neuropsychiatric disease, presents with progressive dementia, psychotic symptoms, depression, and parkinsonian symptoms. The authors report a case illustrating that clozapine, a novel neuroleptic drug, has special efficacy in treating psychotic symptoms in these patients.