Clive Ballard, MD

“There are a lot of harms [with off-label antipsychotics], such as increased mortality, increased strokes, increase of other embolic events, like pulmonary embolism, but also falls, fractures, and accelerated cognitive decline. We also know that those become even more of a problem with long-term usage of these drugs.”

Data from a recent review of 4 studies of pimavanserin (Nuplazid; Acadia Pharmaceuticals) in patients with neurodegenerative disease (NDD) presented at the 

2021 American Academy of Neurology (AAN) Annual Meeting

, April 17-22, by Clive Ballard, MD, professor, age-related diseases, and pro-vice-chancellor and executive dean, University of Exeter Medical School, suggest that patients 

did not experience negative impacts on cognitive function

 with up to 9 months of treatment compared to placebo.

Ballard and colleagues analyzed 4 studies and found that the Mini-Mental State Examination (MMSE) score least squares mean (LSMO change from baseline to week 12) was –0.25 (standard error [SE], 0.42) in study 019 and 0.0 (SE, 0.57) in study 032, and similar to placebo in both. LSM change from baseline to week 8 was 1.2 (SE, 0.21; n = 132) for pimavanserin and 0.5 (SE, 0.21; n = 128) for placebo in the interim analysis of study 046. The mean change from baseline to week 12 was 1.0 (SE, 0.22; n = 145) in the HARMONY study.

 spoke with Ballard to learn more about pimavanserin’s risk-benefit profile and the current use of off-label antipsychotics for the treatment of dementia-related psychosis (DRP). He discussed advantages to the existence of a safer treatment intended for DRP.

Ballard C, Foff EP, Tariot P, et al. Impact of pimavanserin on cognitive measures in patients with neurodegenerative disease (NDD): results from 4 placebo-controlled clinical studies. Presented at 2021 American Academy of Neurology Annual Meeting; April 17-22. Abstract P1 012

Videos

The dean at the University of Exeter Medical School discussed the questions related to treating dementia-related psychosis and the options available. 

Pimavanserin vs Off-Label Psychotics for Dementia-Related Psychosis: Clive Ballard, MD

"We've been looking in some detail over a period of time, about 20 years, of nursing home care, and I think the disappointing thing is that very little has actually changed."

2019 Alzheimer’s Association International Conference

 in Los Angeles, California, Clive Ballard, MD, professor of age-related diseases and Dean of the University of Exeter Medical School spoke with 

in an interview to discuss the state of nursing home care in dementia.

Ballard explained that despite a plethora of policy initiatives over the last 20 years, nothing has changed, and recommends proper staff training in order to improve patients’ quality of life, reduce their psychiatric symptoms, use of drugs, and potentially reduce mortality by increasing positive engagement.

One of the challenges Ballard mentions is how to actually monitor the quality of care in nursing homes. In a detailed evaluation of 24 care homes, Ballard and colleagues reported that 22 of the homes, which were rated as adequate or good, were in need of radical improvement. This is in part because the evaluation of nursing homes focuses on whether an individual’s physical health needs are being met, and while this is important, it doesn’t necessarily capture the real experience the person with dementia living in a care home endures. Ballard concludes that this process of evaluation needs to reflect the social and emotional needs as well as the patients' physical care needs.

The professor of age-related diseases and Dean of the University of Exeter Medical School spoke about the need for proper training of nursing home staff in order to improve quality of life in patients with dementia.

Clive Ballard, MD: The State of Nursing Home Care in Dementia

“If pimavanserin does turn out to be a more effective and safer alternative, that would be a great step forward in treating these distressing symptoms.”

Clive Ballard, MD, professor of age-related diseases and Dean of the University of Exeter Medical School, sat down with 

at the 2018 Alzheimer’s Association International Conference to discuss pimavanserin in subjects with dementia-related psychosis.

At the meeting held in Chicago, Illinois, Ballard presented data on the phase II double-blind, placebo-controlled, trial, Study ACP-103-019, that was designed to evaluate the safety and efficacy of pimavanserin in those with Alzheimer disease psychosis—a more severe population.

On the primary endpoint, the mean change from baseline in the Neuropsychiatric Inventory-Nursing Home Version-Psychosis Score (NPI-NH-PS) at week 6, the study concluded that pimavanserin had a 3.76-point improvement in psychosis versus a 1.93-point improvement in placebo (delta = -1.84, Cohen’s 

= 0.0451). Following the 6-week efficacy evaluation, investigators continued pimavanserin therapy for another 6 weeks to test safety.  

Treatment response ≥30% was observed in 55.2% vs. 37.4% (

= .0159) and for a ≥50% improvement 50.6% vs. 34.1% (

= .0240) for pimavanserin and placebo, respectively. In the post-hoc analysis of those with NPI-NH-PS≥12, a ≥30% improvement was observed in 88.9% vs. 43.3% (

= .0004) and for a ≥50% improvement 77.8% vs. 43.3% (

= .0084) for pimavanserin and placebo, respectively.

Compared with placebo, pimavanserin demonstrated significant benefit in subjects with Alzheimer disease psychosis at the primary endpoint and was found to have an acceptable tolerability profile, and no negative effect on cognition measured by the Mini-Mental State Examination (MMSE).

Pimavanserin has been granted breakthrough therapy designation by the FDA for dementia-related psychosis and researchers are currently conducting HARMONY, a phase III randomized, double-blind, placebo-controlled study, to evaluate the safety and efficacy of pimavanserin for treatment of hallucinations and delusions associated with dementia-related psychosis.

Efficacy was demonstrated in this patient population at the primary endpoint of 6 weeks, especially in those with more severe baseline NPI-NH-PS.

Clive Ballard, MD

Articles

Pimavanserin vs Off-Label Psychotics for Dementia-Related Psychosis: Clive Ballard, MD

Clive Ballard, MD: The State of Nursing Home Care in Dementia

Clive Ballard, MD: Pimavanserin In Patients With Dementia-Related Psychosis