Mixed Results with PD Drug in Alzheimer's Psychosis (CME/CE) | IUK Med Online
Tuesday, August 21, 2018
Home Medical News Mixed Results with PD Drug in Alzheimer's Psychosis (CME/CE)

Mixed Results with PD Drug in Alzheimer's Psychosis (CME/CE)

14
0
SHARE


Medpage Today

Mixed Results with PD Drug in Alzheimer’s Psychosis

Six-week improvement with pimavanserin didn’t endure at 12 weeks

MedpageToday

  • register today

    Earn Free CME Credits by reading the latest medical news in your specialty.

    sign up

  • by Staff Writer, MedPage Today

Action Points

  • Note that this phase II clinical trial found a transient, but short-lived effect of pimavanserin compared with placebo in Alzheimer’s psychosis.
  • By 12 weeks of treatment, no benefit remained in the treated group.

Oral pimavanserin (Nuplazid) demonstrated some efficacy in Alzheimer’s disease psychosis, but only in the short term, according to results of a phase II trial.

The selective 5-HT2A receptor inverse agonist and antagonist met it’s primary efficacy endpoint of reducing psychosis score after 6 weeks of treatment versus placebo (-3.76 points versus -1.93 placebo, 95% CI -3.64 to -0.04, P=0.045), reported Clive Ballard, MD, of Exeter University in England, and colleagues.

However, there was no significant treatment difference found between the groups after 12 weeks of treatment (-0.51, 95% CI -2.23 to 1.21, P=0.561), they wrote in the Lancet Neurology.

In an accompanying commentary, Lon S. Schneider, MD, of the Keck School of Medicine at the University of Southern California in Los Angeles, stated that the findings of this trial “cannot be considered to be positive or clinically meaningful.” He suggested that the “significance of the primary outcome was driven by a worsening of the placebo-treated group at 6 weeks that was not observed at 4 weeks of treatment or at 9 and 12 weeks of treatment.”

Pimavanserin was FDA approved in 2016 for the treatment of delusions and hallucinations caused by psychosis in patients with Parkinson’s disease. Currently, there are no approved treatments specifically for psychosis in people with Alzheimer’s disease, although antipsychotics are often prescribed.

“The occurrence and presence of psychosis in Alzheimer’s disease is associated with more rapid cognitive and functional decline, greater caregiver burden and depression, earlier institutionalisation, and greater treatment-related mortality than having no psychotic symptoms,” Ballard’s group wrote.

They added that use of antipsychotics in Alzheimer’s patients has been tied to adverse side effects, including a faster cognitive decline, and increased risk for stroke, pulmonary embolism, bronchopneumonia, and short-term mortality.

The single-center trial included 181 adults, ages ≥50, recruited from over 100 nursing homes in the U.K. All patients had possible or probable Alzheimer’s disease paired with symptoms of psychosis, including auditory and/or visual hallucinations, and/or delusions.

A total of 90 individuals were assigned to receive two tablets of 17-mg pimavanserin daily and compared with 91 patients who received two tablets of placebo. Exclusion criteria included used of antipsychotics, use of centrally acting anticholinergic treatments, mianserin, cyproheptadine, fluvoxamine, nefazodone, or treatments that prolong the QT interval.

Level of psychosis was measured using the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) psychosis scale. At baseline, roughly a third of both study groups reported severe psychosis, with score of ≥12.

The authors reported no significant differences between treatment groups for the trial’s secondary endpoints — Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change, Cohen-Mansfield Agitation Inventory-Short Form score, NPI-NH agitation/aggression score, and NPI-NH sleep and nighttime behavioral disorder score.

In a subgroup analysis of those with the most severe psychosis, defined as an NPI-NH score of 12+, similar results to the overall group were reported. After 6 weeks of treatment, there were notable improvements seen in the psychosis score for those receiving pimavanserin, although there was no significant advantage seen after 12 weeks.

There were no treatment-related adverse events seen with pimavanserin. The most common adverse events reported among the overall cohort included falls, urinary tract infections, and agitation, which were similar between groups.

“The designation of a primary efficacy outcome at 6 weeks while continuing double-blind treatment for 12 weeks allowed assessment for a continuing effect over 12 weeks, and is a unique feature of this trial,” Schneider commented.

“If the primary outcome had been specified for 12 weeks, typical of previous trials with antipsychotics, then pimavanserin would have been considered as not effective,” he argued, adding that it is “unfortunate” that drugs are often moved along to larger phase III trials despite not showing enough evidence of efficacy in their phase II trials.

Drug developer Acadia Pharmaceuticals is currently recruiting for a phase III clinical trial to assess the efficacy and prevention of the relapse of dementia-related psychotic symptoms.

The study was funded by Acadia Pharmaceuticals.

Ballard disclosed relevant relationships with Acadia Pharmaceuticals, Lundbeck, Heptares, Roche, Lilly, Otsuka, Orion, GlaxoSmithKline, and Pfizer.

Schneider disclosed relevant relationships with the National Institute on Aging, the state of California, Eli Lilly, Lundbeck, Novartis, Biogen, Merck, Roche/Genentech, TauRX, AC Immune, Avraham, Boehringer Ingelheim, Cerespir, Cognition, Neurim, Stemedica, Takeda, vTv, Toyama/FujiFilm, Heptares, Allergan, Axovant, and Impel NeuroPharma.

  • Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
2018-02-13T18:30:00-0500
Take Posttest Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

Mixed Results with PD Drug in Alzheimer's Psychosis

Six-week improvement with pimavanserin didn't endure at 12 weeks

MedpageToday

  • register today

    Earn Free CME Credits by reading the latest medical news in your specialty.

    sign up

  • by Staff Writer, MedPage Today

Action Points

  • Note that this phase II clinical trial found a transient, but short-lived effect of pimavanserin compared with placebo in Alzheimer's psychosis.
  • By 12 weeks of treatment, no benefit remained in the treated group.

Oral pimavanserin (Nuplazid) demonstrated some efficacy in Alzheimer's disease psychosis, but only in the short term, according to results of a phase II trial.

The selective 5-HT2A receptor inverse agonist and antagonist met it's primary efficacy endpoint of reducing psychosis score after 6 weeks of treatment versus placebo (-3.76 points versus -1.93 placebo, 95% CI -3.64 to -0.04, P=0.045), reported Clive Ballard, MD, of Exeter University in England, and colleagues.

However, there was no significant treatment difference found between the groups after 12 weeks of treatment (-0.51, 95% CI -2.23 to 1.21, P=0.561), they wrote in the Lancet Neurology.

In an accompanying commentary, Lon S. Schneider, MD, of the Keck School of Medicine at the University of Southern California in Los Angeles, stated that the findings of this trial "cannot be considered to be positive or clinically meaningful." He suggested that the "significance of the primary outcome was driven by a worsening of the placebo-treated group at 6 weeks that was not observed at 4 weeks of treatment or at 9 and 12 weeks of treatment."

Pimavanserin was FDA approved in 2016 for the treatment of delusions and hallucinations caused by psychosis in patients with Parkinson's disease. Currently, there are no approved treatments specifically for psychosis in people with Alzheimer's disease, although antipsychotics are often prescribed.

"The occurrence and presence of psychosis in Alzheimer's disease is associated with more rapid cognitive and functional decline, greater caregiver burden and depression, earlier institutionalisation, and greater treatment-related mortality than having no psychotic symptoms," Ballard's group wrote.

They added that use of antipsychotics in Alzheimer's patients has been tied to adverse side effects, including a faster cognitive decline, and increased risk for stroke, pulmonary embolism, bronchopneumonia, and short-term mortality.

The single-center trial included 181 adults, ages ≥50, recruited from over 100 nursing homes in the U.K. All patients had possible or probable Alzheimer's disease paired with symptoms of psychosis, including auditory and/or visual hallucinations, and/or delusions.

A total of 90 individuals were assigned to receive two tablets of 17-mg pimavanserin daily and compared with 91 patients who received two tablets of placebo. Exclusion criteria included used of antipsychotics, use of centrally acting anticholinergic treatments, mianserin, cyproheptadine, fluvoxamine, nefazodone, or treatments that prolong the QT interval.

Level of psychosis was measured using the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) psychosis scale. At baseline, roughly a third of both study groups reported severe psychosis, with score of ≥12.

The authors reported no significant differences between treatment groups for the trial's secondary endpoints -- Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change, Cohen-Mansfield Agitation Inventory-Short Form score, NPI-NH agitation/aggression score, and NPI-NH sleep and nighttime behavioral disorder score.

In a subgroup analysis of those with the most severe psychosis, defined as an NPI-NH score of 12+, similar results to the overall group were reported. After 6 weeks of treatment, there were notable improvements seen in the psychosis score for those receiving pimavanserin, although there was no significant advantage seen after 12 weeks.

There were no treatment-related adverse events seen with pimavanserin. The most common adverse events reported among the overall cohort included falls, urinary tract infections, and agitation, which were similar between groups.

"The designation of a primary efficacy outcome at 6 weeks while continuing double-blind treatment for 12 weeks allowed assessment for a continuing effect over 12 weeks, and is a unique feature of this trial," Schneider commented.

"If the primary outcome had been specified for 12 weeks, typical of previous trials with antipsychotics, then pimavanserin would have been considered as not effective," he argued, adding that it is "unfortunate" that drugs are often moved along to larger phase III trials despite not showing enough evidence of efficacy in their phase II trials.

Drug developer Acadia Pharmaceuticals is currently recruiting for a phase III clinical trial to assess the efficacy and prevention of the relapse of dementia-related psychotic symptoms.

The study was funded by Acadia Pharmaceuticals.

Ballard disclosed relevant relationships with Acadia Pharmaceuticals, Lundbeck, Heptares, Roche, Lilly, Otsuka, Orion, GlaxoSmithKline, and Pfizer.

Schneider disclosed relevant relationships with the National Institute on Aging, the state of California, Eli Lilly, Lundbeck, Novartis, Biogen, Merck, Roche/Genentech, TauRX, AC Immune, Avraham, Boehringer Ingelheim, Cerespir, Cognition, Neurim, Stemedica, Takeda, vTv, Toyama/FujiFilm, Heptares, Allergan, Axovant, and Impel NeuroPharma.

  • Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
2018-02-13T18:30:00-0500
Take Posttest Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



Source link

LEAVE A REPLY

Please enter your comment!
Please enter your name here