American Academy of Neurology (AAN) 65th Annual Meeting

March 16-23, 2013; San Diego, CA

Post-hoc Analysis Shows Extended-Release Memantine Improves Behavioral Symptoms Across Alzheimer’s Disease Severities

Behavioral symptoms are common among persons with Alzheimer’s disease (AD) and become more prevalent and pronounced as the disease progresses. These symptoms can be distressing for patients, caregivers, and other residents if the patient resides in a long-term care facility. Antipsychotics are often prescribed to manage behavioral symptoms in patients with AD, and although these drugs are generally effective, their use is associated with increased safety risks, leading physicians to look for safer strategies to effectively manage these symptoms. Antidementia drugs are one class of agents that are increasingly being investigated as one such strategy. During an abstract session at the AAN annual meeting, Michael Tocco, PhD, associate director, Medical Affairs, Forest Research Institute, Jersey City, NJ, and colleagues reported that the new extended-release (ER) formulation for the antidementia agent memantine could significantly improve behavioral symptoms across a wide range of baseline AD severities, from moderate to severe disease.

Tocco and colleagues’ findings came from a post-hoc analysis of their 24-week, randomized, placebo-controlled trial (NCT00322153) that evaluated the safety, tolerability, and efficacy of memantine compared with placebo in outpatients with moderate to severe AD who were on stable acetylcholinesterase inhibitor therapy. In the trial, patients had been randomly assigned to receive a placebo (n=335) or memantine ER 28 mg once daily (n=342) in addition to their acetylcholinesterase inhibitor. The severity of their baseline dementia had been established using the Mini-Mental State Examination (MMSE). The post-hoc analysis included 540 patients (memantine n=268; placebo n=272) who had available data on the Neuropsychiatric Inventory (NPI) at week 24.  A mixed model repeated measures analysis was performed to assess baseline-to-endpoint changes on the NPI for each treatment group based on their individual baseline MMSE scores, which ranged from 4 to 17.

At week 24, the study’s end point, memantine ER was associated with mean improvement on the NPI compared with placebo across all baseline MMSE scores, but reached statistical significance (P<.05) for those with scores ranging from 7 to 14. The researchers reported that mean between-group differences ranged from 2.7 to 3.1 points, and that outlying score ranges were limited by small n values (ie, low statistical power).

“This study adds to the body of literature indicating that antidementia agents, particularly memantine, offer a safe and effective treatment option that may help benefit behavioral symptoms in patients with moderate to severe Alzheimer’s disease,” noted Tocco in an interview with Annals of Long-Term Care.^®—Christina T. Loguidice

This study was supported by Forest Laboratories, Inc.

Lacosamide Well Tolerated for the Long-Term Treatment of Partial-Onset Seizures in Older Adults

The active epilepsy prevalence rate among persons 65 years and older is approximately 1.5%, which is about twice the rate encountered among younger adults. In older adults, partial-onset seizures are the most common form of epilepsy, but although epilepsy is more prevalent in this population than in other patient populations, little is known about how epilepsy treatments, including those for partial-onset seizures, affect these patients, who tend to have a high rate of comorbidities and polypharmacy. During the AAN annual meeting, William E. Rosenfeld, MD, neurologist/epileptologist, The Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, and colleagues presented the results of their study, which assessed whether the antiepileptic agent lacosamide is an appropriate long-term treatment for elders with partial-onset seizures.

“After reviewing data from three OLE [open-label extension] trials, we found that long-term lacosamide treatment of up to 8 years was generally well tolerated by patients aged 65 years and older,” said Rosenfeld in an interview with Annals of Long-Term Care.^® “These elderly patients experienced fewer seizures and lacosamide maintained efficacy over the long term similar to the overall OLE patient pool,” he noted.

Rosenfeld and colleagues pooled data from OLE trials NCT00522275, NCT00552305, and NCT00515619, which cumulatively included 1054 adults with partial-onset seizures who completed a lead-in trial of adjunctive lacosamide, and they evaluated the outcomes for the subset of patients who were 65 years and older. This included 33 (3.1%) patients who were at least 65 years of age by the end of the OLE studies.

Of these 33 patients, 21 (63.6%) completed the OLE trials, 18 (85.7%) of who continued on to receive commercial lacosamide treatment. The mean and maximum lacosamide treatment durations were 1563.2 and 2790.0 days, respectively, with a median modal dose of 400-mg daily. All patients had an opportunity to receive at least 3 years (and up to 8 years) of open-label lacosamide treatment, and after 1, 3, and 5 years of this treatment, 90.9%, 75.8%, and 42.4% of elderly patients remained in the trial, respectively.

Patients who discontinued treatment did so primarily because of adverse events (n=4; 12.1%), lack of efficacy (n=3; 9.1%), and consent withdrawal (n=2; 6.1%). The median percent reduction in seizure frequency from baseline was 62.5%, 58.2%, and 66.6% after 1, 3, and 5 years, respectively. Reported adverse effects included dizziness (n=12; 36.4%); falls (n=9; 27.3%); contusion or sinusitis (n=7 each; 21.2%); cognitive disorder, tremor, headache, depression, or cough (n=6 each; 18.2%); and urinary tract infection, nausea, diplopia, blurred vision, convulsion, balance disorder, or extremity pain (n=5 each; 15.2%).

“In this small subset of elderly patients, lacosamide appears to be well tolerated and efficacious. Lacosamide could be of potential benefit to the elderly in general as well as for those patients in long-term care facilities,” noted Rosenfeld. —Christina T. Loguidice

The three OLE studies and this analysis were supported by UCB Pharma.