Open label, multicenter, 28-week extension study of the safety and tolerability of memantine in patients with mild to moderate Alzheimer's disease.

BACKGROUND: Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be safe and to have beneficial effects on cognition, function, behavior, and global patient status in patients with Alzheimer's disease (AD) in studies lasting 3-6 months. It is approved in the U.S. and Europe for the treatment of moderate to severe AD and is currently under investigation for mild to moderate AD. OBJECTIVE: To evaluate the long-term safety of memantine in patients with mild to moderate AD and to investigate the tolerability of once-daily dose administration. METHODS: This 28-week study enrolled 314 patients with mild to moderate AD who had completed a 24-week, double-blind, placebo-controlled lead-in clinical trial of memantine in AD. Following an 8-week double-blind dose titration phase (used to assess the tolerability of different dosing regimens), subjects were assigned to continuous open label memantine (10 mg, bi.d.) treatment for 20 weeks. Safety outcome measures included treatment-emergent adverse events (AEs), deaths, vital signs, electrocardiograms, and laboratory parameters. RESULTS: During the 28-week study (Phase A+Phase B), the most common AEs were falls and other injuries (both 10.8%). AEs resulted in treatment discontinuation in 6.7% of patients. Discontinuations due to AEs were similar in the once-daily dosing groups compared to the twice-daily dosing groups. During dose titration, completion rates were greater than 90% for both groups. Conversion to once-daily dosing in patients already receiving twice-daily doses of memantine was also well tolerated. CONCLUSIONS: Memantine monotherapy in patients with mild to moderate AD is safe and well tolerated for at least one year. Once-daily dosing during titration and short-term maintenance therapy is safe and well tolerated.

Effect of divalproex sodium on behavioural and cognitive problems in elderly dementia.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) occur in up to 90% of individuals with dementia at some point in their illness. BPSD reduce patient quality of life, cause great distress to caregivers and are the most common reason for institutionalisation. In nursing homes, pharmacological measures (usually antipsychotics or benzodiazepines) are often required to control agitation and aggression in patients with dementia. However, no medications have been approved by the US Food and Drug Administration for this indication as yet. The antiepileptic agent divalproex sodium may have advantages in this setting because of lower rates of drug interactions and adverse effects in this patient population. OBJECTIVE: The aim of the study was to assess the impact of treatment with divalproex sodium on behavioural, mood and cognitive measures in a population of elderly nursing home residents with a history of behaviour problems associated with dementia. MATERIALS AND METHODS: The study was a retrospective analysis of a long-term care database which allowed assessment of the impact of divalproex sodium therapy on behavioural, mood and cognitive measures in elderly nursing home residents with a history of dementia-related behaviour problems. Minimum Data Set items relating to problems of behaviour, cognition and mood were collected prior to and after divalproex sodium treatment over a 1-year period. Two-phase generalised linear regression, with fixed intersections at the time of divalproex sodium initiation, was used to estimate trends in each measure prior to and after divalproex sodium initiation. Monotherapy, combination therapy with benzodiazepines and antipsychotics, and dose comparisons of divalproex sodium were studied. RESULTS: In all three situations (i.e. as monotherapy, in combination with benzodiazepines and antipsychotics, and at both higher and lower doses), divalproex sodium therapy was shown to have multiple beneficial effects on various behavioural, mood and cognition indicators in elderly nursing home residents. In general, the data seemed to support more favourable results for the higher divalproex sodium dose group. CONCLUSIONS: These data support the use of divalproex sodium in elderly nursing home residents with a history of dementia and behaviour problems and warrant conduct of prospective, randomised trials of the drug in this setting.

Retrospective cohort study of venlafaxine, fluoxetine or sertraline in long-term care.

OBJECTIVE: To describe the effects of venlafaxine, fluoxetine and sertraline treatment on mood and behaviour patterns, physical functioning, and tolerability issues in a long-term care environment. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort analysis of 257 elderly residents of three long-term care facilities in the US who used venlafaxine, fluoxetine or sertraline during a 3-month period. MAIN OUTCOME MEASURES: Indicators of depression, anxiety and sad mood, physical functioning, antidepressant-related adverse events, and the global impression of efficacy. RESULTS: The average age of the participants was 80.6 years. At the 3-month follow-up, more than 85% of the residents recorded no change in indicators of depression, anxiety and sad mood or physical functioning, and there were no statistically significant differences among the three antidepressant drug groups. A marginal improvement in the social interaction indicator was observed among residents who received venlafaxine (11%) compared with those receiving fluox-etine (3%) or sertraline (2%). Antidepressant-related adverse events were infrequent and similar in incidence across the three drug groups. CONCLUSIONS: Indicators of mood and functioning of most residents were stable over the 3-month period and similar among the venlafaxine, fluoxetine and sertraline groups, and no significant differences in the safety profiles of the three drugs were recorded.