Pimavanserin in Alzheimer's Disease Psychosis: Efficacy in Patients with More Pronounced Psychotic Symptoms.

BACKGROUND: Pimavanserin is a 5-HT2A receptor inverse agonist/antagonist and is approved in the United States for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. OBJECTIVE: Evaluate the efficacy of pimavanserin on symptoms of psychosis in patients with Alzheimer's disease (AD). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Nursing home residents. PARTICIPANTS: Patients with AD psychosis. INTERVENTIONS: Pimavanserin 34 mg or placebo daily for 12 weeks. MEASUREMENTS: The primary endpoint was mean change from baseline at Week 6 on the Neuropsychiatric Inventory-Nursing Home Version psychosis score (NPI-NH-PS). In the prespecified subgroup analysis, the mean change in NPI-NH-PS and the responder rates among those with baseline NPI-NH-PS ≥12 were evaluated. RESULTS: Of 181 patients randomized (n=90 pimavanserin; n=91 placebo), 57 had baseline NPI-NH-PS ≥12 (n=27 pimavanserin; n=30 placebo). In this severe subgroup, large treatment effects were observed (delta=-4.43, Cohen's d=-0.73, p=0.011), and ≥30% improvement was 88.9% vs. 43.3% (p<0.001) and ≥50% improvement was 77.8% vs. 43.3% (p=0.008) for pimavanserin and placebo, respectively. The rate of adverse events (AEs) in the severe subgroup was similar between treatment groups, and urinary tract infection, fall, and agitation were most frequent. Serious AEs was similar with pimavanserin (17.9%) and placebo (16.7%) with fewer discontinuations due to AEs with pimavanserin (7.1%) compared to placebo (10.0%). Minimal change from baseline occurred for the mean MMSE score over 12 weeks. CONCLUSIONS: Pimavanserin demonstrated significant efficacy in AD psychosis in patients with higher baseline severity of psychotic symptoms (NPI-NH-PS ≥12). Treatment with pimavanserin showed an acceptable tolerability profile.

Efficacy of laser-assisted uvulopalatoplasty in obstructive sleep apnea.

Laser-assisted uvulopalatoplasty (LAUP) enlarges the oropharyngeal airway by reshaping the uvula, soft palate, and tonsillar pillars. In contrast to a uvulopalatopharyngoplasty performed in the operating room, LAUP is staged over several office visits, is less costly, is bloodless, and is not associated with velopharyngeal insufficiency or stenosis. Previous studies have documented the efficacy of LAUP in the treatment of snoring. We explore the efficacy of LAUP in the treatment of obstructive sleep apnea. Forty-eight patients comprised the study group. Each patient snored, exhibited >50% palatal collapse on Müller's maneuver, and had nocturnal polysomnography showing a respiratory disturbance index (RDI) >10. Each patient underwent LAUP until he or she reported that snoring had ceased. Of the 29 patients who underwent post-LAUP nocturnal polysomnography, 7 had RDIs <10, oxygen saturation >86%, and no cardiac arrhythmias. LAUP reduced RDI to <10 in patients with pre-LAUP apnea indexes <3 (P = 0.05) or pre-LAUP RDIs <30 (P = 0.01). The following variables did not correlate with the success of LAUP in treating obstructive sleep apnea: age, sex, pre-LAUP weight, pre-LAUP body mass index, perioperative weight change, perioperative body mass index change, pre-LAUP snoring, and post-LAUP snoring. We conclude that LAUP is an effective means of treating patients with RDIs <30.

A normative study of the maintenance of wakefulness test (MWT).

The maintenance of wakefulness test (MWT) is a daytime polysomnographic procedure which quantifies wake tendency by measuring the ability to remain awake during soporific circumstances. We present normative data based on 64 healthy subjects (27 males and 37 females) who adhered to uniform MWT procedural conditions including polysomnographic montage, illuminance level, seating position, room temperature, meal timing, and subject instructions. When allowed a maximum trial duration of 40 min, subjects' mean sleep latency to the first epoch of sustained sleep was 35.2 +/- 7.9 min. The lower normal limit, defined as two standard deviations below the mean, was 19.4 min. Calculation of data on the basis of a maximum trial duration of 20 min and sleep latency to the first appearance of brief sleep (a microsleep episode or one epoch of any stage of sleep) yielded a mean sleep latency of 18.1 +/- 3.6 min and a lower normal limit of 10.9 min. Sleep latency scores were significantly higher than those previously reported in patients with disorders of excessive somnolence. Therefore, the MWT appears to be a useful procedure in differentiating groups with normal daytime wake tendency from those with impaired wake tendency and in identifying individuals with pathologic inability to remain awake under soporific circumstances.