The safety and tolerability of aripiprazole once-monthly as maintenance treatment for bipolar I disorder: A double-blind, placebo-controlled, randomized withdrawal study.

BACKGROUND: Aripiprazole once-monthly 400 mg (AOM 400), an atypical long-acting injectable antipsychotic, has demonstrated efficacy and safety in maintenance treatment of bipolar I disorder (BP-I). We further assess safety and tolerability and characterize adverse events (AEs) across the duration of aripiprazole exposure. METHODS: Patients with BP-I were stabilized on oral aripiprazole (2-8 weeks), AOM 400 (12-28 weeks), followed by 1:1 randomization of patients meeting stability criteria to a 52-week, double-blind, placebo-controlled withdrawal phase. Treatment-emergent AEs (TEAEs) were collected across study phases. AEs were counted in a phase if they were drug-related and continued from the baseline of that phase. A separate analysis on new-onset akathisia was conducted. RESULTS: Among TEAEs occurring in ≥10% of patients during all study phases were akathisia (23.3%) and weight increased (10.6%). Median time to akathisia onset was 20 days after starting oral aripiprazole; median duration was 29 days for the first occurrence; 21/168 patients (12.5%) reporting akathisia experienced >1 episode. Episodes of new-onset akathisia decreased over time, with few events reported in the randomized phase. Weight gain was minimal with oral aripiprazole, generally starting within 3 months after the first AOM 400 injection, and appearing to plateau at 36 weeks. The mean weight gain within any study phase was ≤1.0 kg. Potentially clinically significant changes in metabolic parameters were uncommon. LIMITATIONS: Patients on placebo had AOM 400 exposure before randomization. CONCLUSION: These findings suggest that AEs with AOM 400 treatment were time-limited and support AOM 400 as a well-tolerated maintenance treatment of BP-I.

Digital technologies as biomarkers, clinical outcomes assessment, and recruitment tools in Alzheimer's disease clinical trials.

Digital technology is transforming the development of drugs for Alzheimer's disease and was the topic of the Alzheimer's Association's Research Roundtable on its May 23-24, 2017 meeting. Research indicates that wearable devices and unobtrusive passive sensors that enable the collection of frequent or continuous, objective, and multidimensional data during daily activities may capture subtle changes in cognition and functional capacity long before the onset of dementia. The potential to exploit these technologies to improve clinical trials as both recruitment and retention tools as well as for potential end points was discussed. The implications for the collection and use of large amounts of data, lessons learned from other related disease areas, ethical concerns raised by these new technologies, and regulatory issues were also covered in the meeting. Finally, the challenges and opportunities of these new technologies for future use were discussed.

Aripiprazole once-monthly as maintenance treatment for bipolar I disorder: a 52-week, multicenter, open-label study.

BACKGROUND: The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. METHODS: This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. RESULTS: Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (< 10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. CONCLUSION: AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.

Symptoms and functioning with aripiprazole once-monthly injection as maintenance treatment for bipolar I disorder.

BACKGROUND: Effects of maintenance treatment with aripiprazole once-monthly 400mg (AOM 400) on symptoms and functioning were assessed in adults with bipolar I disorder (BP-I) after a manic episode. METHODS: Patients were stabilized on oral aripiprazole, cross-titrated to AOM 400, then randomized in a 52-week, double-blind, placebo-controlled, withdrawal phase. Prespecified secondary outcomes are reported: time to hospitalization for mood episode, Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression-Bipolar scale, Functioning Assessment Short Test (FAST), and Brief Quality of Life in Bipolar Disorder questionnaire. Time to hospitalization for mood episode was analyzed using log-rank test and changes from baseline using mixed model for repeated measures or analysis of covariance. RESULTS: AOM 400 significantly increased time to hospitalization for any mood episode versus placebo (P=0.0002). YMRS total scores decreased with oral aripiprazole; improvements were maintained with AOM 400. After randomization, YMRS scores changed little with AOM 400 but worsened with placebo (P=0.0016), and MADRS scores, already low at trial initiation, did not differ between groups. FAST score improvements were maintained with AOM 400 but not placebo (P=0.0287). LIMITATIONS: Results are generalizable to patients with BP-I stabilized on aripiprazole following a manic episode. CONCLUSIONS: Patients with BP-I experiencing an acute manic episode exhibited symptomatic and functional improvements during stabilization with oral aripiprazole and AOM 400 that were maintained with continued AOM 400 treatment but not placebo. AOM 400 is the first once-monthly long-acting injectable antipsychotic to demonstrate efficacy in maintenance treatment of the manic phase of BP-I.

Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment paradigms.

Neuropsychiatric symptoms (NPSs) are hallmarks of Alzheimer's disease (AD), causing substantial distress for both people with dementia and their caregivers, and contributing to early institutionalization. They are among the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, yet are under-recognized and often challenging to treat. With this in mind, the Alzheimer's Association convened a Research Roundtable in May 2016, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of NPSs and review the development of therapeutics and biomarkers of NPSs in AD. This review will explore the neurobiology of NPSs in AD and specific symptoms common in AD such as psychosis, agitation, apathy, depression, and sleep disturbances. In addition, clinical trial designs for NPSs in AD and regulatory considerations will be discussed.

Efficacy and Safety of Aripiprazole Once-Monthly in the Maintenance Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled, 52-Week Randomized Withdrawal Study.

OBJECTIVE: To evaluate efficacy, safety, and tolerability of long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) as maintenance treatment for bipolar I disorder (BP-I). METHODS: In a double-blind, placebo-controlled, 52-week randomized withdrawal study conducted from August 2012 to April 2016, patients with a DSM-IV-TR diagnosis of BP-I currently experiencing a manic episode were stabilized sequentially on oral aripiprazole and AOM 400 and then randomized to AOM 400 or placebo. The primary end point was time from randomization to recurrence of any mood episode. Other end points included proportion of patients with recurrence of any mood episode and recurrence by mood episode type. RESULTS: Of 266 randomized patients, 64 (48.1%) of 133 in the AOM 400 group and 38 (28.6%) of 133 in the placebo group completed the study. AOM 400 significantly delayed the time to recurrence of any mood episode compared with placebo (hazard ratio: 0.45; 95% CI, 0.30 to 0.68; P < .0001). Significantly fewer patients (P < .0001) experienced recurrence of any mood episode with AOM 400 (35/132; 26.5%) compared with placebo (68/133; 51.1%), with the effects observed predominantly on manic episodes (P < .0001). Patients were not depressed at study entry, and between-group differences in depressive episodes were not significant (P < .864). The treatment-emergent adverse events (incidence > 5%) that were reported at higher rates with AOM 400 than placebo were weight increase, akathisia, insomnia, and anxiety. CONCLUSIONS: AOM 400 delayed the time to and reduced the rate of recurrence of mood episodes and was generally safe and well tolerated. These findings support the use of AOM 400 for maintenance treatment of BP-I. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01567527.

A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder.

OBJECTIVE: To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients. METHOD: This multicenter, double-blind, randomized, placebo-controlled, relapse-prevention trial enrolled patients (6-17 years) who met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DMS-IV-TR) criteria for autistic disorder and who also had serious behavioral problems (ie, tantrums, aggression, self-injurious behavior, or a combination of these behavioral problems) between March 2011 and June 2012. In phase 1, single-blind aripiprazole was flexibly dosed (2-15 mg/d) for 13-26 weeks. Patients with a stable response (≥ 25% decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of "much improved" or "very much improved" on the Clinical Global Impressions-Improvement scale) for 12 consecutive weeks were randomized into phase 2 to continue aripiprazole or switch to placebo. Treatment was continued until relapse or up to 16 weeks. The primary end point was time from randomization to relapse. RESULTS: Eighty-five patients were randomized in phase 2. The difference in time to relapse between aripiprazole and placebo was not statistically significant (P = .097). Kaplan-Meier relapse rates at week 16 were 35% for aripiprazole and 52% for placebo (hazard ratio [HR] = 0.57; number needed to treat [NNT] = 6). The most common adverse events during phase 1 were weight increase (25.2%), somnolence (14.8%), and vomiting (14.2%); and, during phase 2 (aripiprazole vs placebo), they were upper respiratory tract infection (10.3% vs 2.3%), constipation (5.1% vs 0%), and movement disorder (5.1% vs 0%). CONCLUSIONS: In this study, there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy. However, the HR and NNT suggest some patients will benefit from maintenance treatment. Patients receiving aripiprazole should be periodically reassessed to determine the continued need for treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01227668.

Safety of paliperidone extended-release in patients with schizophrenia or schizoaffective disorder and hepatic disease.

BACKGROUND/PURPOSE: Patients with schizophrenia often suffer from comorbid hepatic disease. This multicenter, open-label, single-arm, crossover study evaluated the safety and efficacy of paliperidone extended-release (ER) in patients with schizophrenia or schizoaffective disorder and hepatic disease. METHODS: The study comprised a screening period, followed by 9 weeks' open-label treatment, divided into 2 phases. Phase 1 (4 weeks) was a continuation of usual antipsychotic treatment (UAT); phase 2 (5 weeks) consisted of a 1-week cross-titration from UAT to flexibly dosed paliperidone ER (3-12 mg/d), followed by 4 weeks of paliperidone ER alone. Treatment-emergent adverse events (TEAEs), including those considered more relevant to antipsychotic treatment (prespecified adverse events [AEs]), were analyzed. RESULTS: Although more subjects reported TEAEs during the paliperidone ER alone period than during the UAT period, no significant differences occurred in prespecified AE rates. No new safety signals were detected, and minimal shifts in liver function test values were observed. Improvements in psychiatric symptoms and functioning were observed after 4 weeks' paliperidone ER treatment. CONCLUSIONS: This study suggests that paliperidone ER is well tolerated in patients with schizophrenia or schizoaffective disorder and hepatic disease. To the best of our knowledge, this is the largest prospective study to date in this population.

Neuropsychiatric symptoms in Alzheimer's disease.

Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these symptoms are currently known to manifest commonly in very early disease and in prodromal phases, such as mild cognitive impairment. Despite decades of research, reliable treatments for dementia-associated NPS have not been found, and those that are in widespread use present notable risks for people using these medications. An Alzheimer's Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer's disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics.

Paliperidone extended-release tablets in patients with recently diagnosed schizophrenia.

AIM: Effective early and persistent antipsychotic treatment in recently diagnosed schizophrenia may positively impact long-term outcomes. Paliperidone extended-release (ER) was assessed in this population. METHODS: Post hoc analysis of pooled data from three 6-week, double-blind (DB), placebo-controlled, and three 1-year open-label (OL) studies of paliperidone ER in schizophrenia patients. Data stratified by time since diagnosis (< or =3 vs. >3 years). RESULTS: At DB (n = 1193) and OL baselines (n = 744), 259 (21.9%) and 188 (25.3%) patients were diagnosed < or =3 years. At DB end point, both populations improved with paliperidone ER versus placebo on Positive and Negative Syndrome Scale (PANSS) total, Clinical Global Impressions-Severity and Personal and Social Performance (PSP) scale scores (all P < 0.05). At OL end point, there were significant improvements from DB baseline in both populations on these scales (P < 0.0001), with greater improvement in the < or =3-year population on PANSS total (P < 0.001) and PSP (P < 0.001) scores. During DB treatment, only the < or =3-year population reported adverse events (AEs) in > or =5% (placebo-adjusted rate) of subjects receiving paliperidone ER: akathisia, extrapyramidal disorder not otherwise specified and somnolence. During OL treatment, akathisia and somnolence occurred more frequently (> or =5%) in the < or =3- versus >3-year population. OL study completion rates were 51.1% in < or =3-year, and 48.2% in >3-year subjects. CONCLUSIONS: Paliperidone ER significantly improved symptoms and functioning in schizophrenia patients, regardless of time since diagnosis. Recently diagnosed patients who continued treatment exhibited greater symptom reduction and functional benefit over the long term. Results also suggest that these patients may be more susceptible to certain AEs.

Seizures in Alzheimer disease: who, when, and how common?

BACKGROUND: Transient symptoms in Alzheimer disease (AD) are frequent and include seizures, syncope, and episodes of inattention or confusion. The incidence of seizures in AD and predictors of which patients with AD might be more predisposed to them is based primarily on retrospective studies and is not well established. OBJECTIVE: To determine the incidence and predictors of new-onset unprovoked seizures. DESIGN: Prospective cohort study. SETTING: Three academic centers. Patients Four hundred fifty-three patients with probable AD observed prospectively from mild disease stages since 1992. Main Outcome Measure Informant interviews every 6 months included questions about whether the patient had a seizure (convulsion, fainting, or "funny" spell) and whether diagnosis or treatment for epilepsy or seizure was made. Two epileptologists independently retrospectively reviewed all available medical records for 52 patients with positive responses to either of these questions, and using a specific checklist form, events were diagnosed as to whether they were unprovoked seizures (intrarater concordance, kappa = 0.67). Diagnosis of unprovoked seizures constituted the event in survival analyses. Potential predictors included sex, age, race/ethnicity, educational achievement, duration of illness, baseline cognition and function, depression, medical comorbidities, and time-dependent use of cholinesterase inhibitors and neuroleptic agents, apolipoprotein E genotype, and previous electroencephalographic findings. RESULTS: Over the course of 3518 visit-assessments (per patient: mean, 7.8; maximum, 27), 7 patients (1.5%) developed seizures. Younger age was associated with higher risk (hazard ratio, 1.23; 95% confidence interval, 1.08-1.41; P = .003 for each additional year of age) of seizure incidence. No other predictor was significant. The overall incidence of seizures was low (418 per 100 000 person-years of observation) although significantly higher than expected for idiopathic unprovoked seizures in similar age ranges of the general population (hazard ratio, 8.06; 95% confidence interval, 3.23-16.61). CONCLUSIONS: Unprovoked seizures are uncommon in AD, but they do occur more frequently than in the general population. Younger age is a risk factor for seizures in AD.

Scales as outcome measures for Alzheimer's disease.

The assessment of patient outcomes in clinical trials of new therapeutics for Alzheimer's disease (AD) continues to evolve. In addition to assessing drugs for symptomatic relief, an increasing number of trials are focusing on potential disease-modifying agents. Moreover, participants with AD are being studied earlier in their course of disease. As a result, the limitations of current outcome measures have become more apparent, as has the need for better instruments. In recognition of the need to review and possibly revise current assessment measures, the Alzheimer's Association, in cooperation with industry leaders and academic investigators, convened a Research Roundtable meeting devoted to scales as outcome measures for AD clinical trials. The meeting included a discussion of methodological issues in the use of scales in AD clinical trials, including cross-cultural issues. Specific topics related to the use of cognitive, functional, global, and neuropsychiatric scales were also presented. Speakers also addressed academic and industry initiatives for pooling data from untreated and placebo-treated patients in clinical trials. A number of regulatory topics were also discussed with agency representatives. Panel discussions highlighted areas of controversy, in an effort to gain consensus on various topics.

One-week dose titration of extended release galantamine in patients with Alzheimer's disease.

BACKGROUND: Our purpose was to assess the safety and tolerability of extended-release galantamine (GAL-ER), using a 1-week dose titration in Alzheimer's patients. METHODS: An open-label, 12-week, multicenter study was performed (n = 82). Results were compared with findings from a placebo-controlled trial using a 4-week titration of GAL-ER and immediate-release galantamine. The primary analysis compared incidences of adverse events (AEs). RESULTS: Although not statistically significant, more patients in the 1-week titration study experienced an AE. More patients with a 1-week titration had at least one prespecified gastrointestinal (GI) AE. These findings correlated with a higher baseline incidence of GI disturbances. Four patients experienced serious AEs; no deaths occurred. Mean Mini-Mental State Examination scores improved by 1.8 and 1.9 points at weeks 4 and 12, respectively. CONCLUSIONS: A 1-week titration of GAL-ER was generally safe and well tolerated, with a potential risk of more GI side effects. A 1-week titration may permit dosing flexibility and promote increased adherence to medication regimens.

Effects of galantamine on measures of attention: results from 2 clinical trials in Alzheimer disease patients with comparisons to donepezil.

Deficits in attention are present early in the course of Alzheimer disease (AD). Acetylcholine receptors are appealing molecular targets for intervention as cholinergic pathways are involved in the neurobiology of attention. For this reason, measures of attention were included in 2 independent, multicenter, randomized, parallel, controlled trials in subjects with AD comparing the effects of galantamine, an acetylcholinesterase inhibitor and postulated nicotinic receptor modulator, and donepezil, an acetylcholinesterase inhibitor. The attention battery of the Cognitive Drug Research computerized assessment system was used in both trials. Small magnitude, positive signals were observed for simple and choice reaction times for both compounds. Attention task performance tended to improve early for galantamine-treated subjects. A consistent temporal pattern of improvement was not observed in donepezil-treated subjects. Quantitative findings appeared more pronounced in subjects with moderate AD. Galantamine's proposed action as a nicotinic receptor modulator may bear on these findings. Improved attention may have positive effects on cognitive and functional outcomes for AD patients, although this hypothesis requires further study and validation.

Beyond in vitro data: a review of in vivo evidence regarding the allosteric potentiating effect of galantamine on nicotinic acetylcholine receptors in Alzheimer's neuropathology.

Galantamine is an approved treatment for mild to moderate Alzheimer's disease, with demonstrated benefits for cognition and functional ability in human studies. The mechanism of action that is most generally recognized as underlying the clinical benefits of galantamine is inhibition of brain acetylcholinesterase (AChE). However, an increasing body of evidence suggests that an additional mechanism, most likely allosteric modulation of nicotinic acetylcholine receptors (nAChRs), may contribute to the therapeutic effects of galantamine. This review summarizes the research on this additional mechanism, with emphasis on data derived from in vivo animal studies and open-label hypothesis-generating studies in humans. In general, these studies provide evidence of effects beyond those of AChE inhibition alone, most notably in comparisons with other AChE inhibitors, in which galantamine produced similar or greater effects at doses that provided lower levels of brain AChE inhibition. The use of nAChR agonists and antagonists in some of these studies lends support to the proposed allosteric potentiating ligand activity of galantamine at nAChRs. This dual action of galantamine may account for its therapeutic profile.

Effects of statins on cognitive function in patients with Alzheimer's disease in galantamine clinical trials.

BACKGROUND AND OBJECTIVE: A number of reports have been published on the possible involvement of changes in brain cholesterol metabolism in the origin of Alzheimer's disease (AD) and the potential for influencing these changes by administration of HMG-CoA reductase inhibitors ('statins'). The aim of this study was to evaluate a potential association between use of statins and maintenance of cognitive function in patients with AD in galantamine clinical trials. METHOD: A post hoc analysis was conducted on data pooled from three double-blind, placebo-controlled, clinical trials of galantamine in patients with AD. Patients were divided into four treatment groups: statin plus galantamine (n = 42), statin alone (n = 50), galantamine alone (n = 614) or neither galantamine nor statin (n = 619). RESULTS: Galantamine was associated with a significant beneficial effect on cognitive status (p < 0.001). The association of use of statins with changes in cognitive status was not significant (p = 0.083). There was no significant interaction between the effects on cognition of statins and galantamine (p = 0.183) and no statistically significant changes in adverse effect rates were observed. CONCLUSION: These findings suggest the need for larger long-term trials to confirm or refute possible effects of statins on cognitive function and the potential interaction of statins with acetylcholinesterase inhibitors in the treatment of AD.

Incidence and predictors of seizures in patients with Alzheimer's disease.

PURPOSE: To determine cumulative incidence and predictors of new-onset seizures in mild Alzheimer's disease (AD) with a cohort followed prospectively. Limited information is available on the incidence of seizures, and no reports exist of seizure predictors in AD patients. METHODS: Mild AD patients were prospectively followed at 6-month intervals to estimate incidence of unprovoked seizures, compare age-specific risk of unprovoked seizures with population norms, and identify characteristics at baseline (demographics, duration and severity of AD, physical and diagnostic test findings, and comorbid medical and psychiatric conditions) influencing unprovoked seizure risk. Review of study charts and medical records supplemented coded end-point data. RESULTS: The cumulative incidence of unprovoked seizures at 7 years was nearly 8%. In all age groups, risk was increased compared with a standard population, with an 87-fold increase in the youngest group (age 50-59 years) and more than a threefold increase in the oldest group (age 85+ years). In multivariate modeling, independent predictors of unprovoked seizures were younger age [relative risk (RR), 0.89 per year increase in age; 95% confidence interval (CI), 0.82-0.97], African-American ethnic background (RR, 7.35; 95% CI, 1.42-37.98), more-severe dementia (RR, 4.15; 95% CI, 1.06-16.27), and focal epileptiform findings on electroencephalogram (EEG) (RR, 73.36; 95% CI, 1.75-3075.25). CONCLUSIONS: Seizure incidence is increased in people starting with mild-to-moderate AD. Younger individuals, African Americans, and those with more-severe disease or focal epileptiform findings on EEG were more likely to have unprovoked seizures.

Effects of galantamine versus donepezil on sleep in patients with mild to moderate Alzheimer disease and their caregivers: a double-blind, head-to-head, randomized pilot study.

OBJECTIVE: To examine the effects of galantamine and donepezil on patient and caregiver sleep. METHODS: In this randomized, 8-week, double-blind, parallel-group, multicenter, pilot comparison of galantamine and donepezil, safety and efficacy data were collected. Objective and subjective changes in sleep of patients (N = 63) and their caregivers were measured. Clinicians assessed changes in patient global function. As this was a pilot study, only descriptive statistics are presented. RESULTS: In general, neither galantamine nor donepezil, at stable doses, were associated with decrements in actigraphy sleep measurements. However, mean scores in all measures of sleep showed a tendency for minimal improvements in galantamine-treated patients and minimal decrements in the donepezil-treated patients. The same tendencies were present in caregiver sleep measures. Global function either improved or remained stable in a higher percentage of patients treated with galantamine than with donepezil. Galantamine and donepezil were both well tolerated and safe. CONCLUSIONS: This pilot study was the first to compare the effects of these drugs on sleep in patients or caregivers. Both drugs were safe and well tolerated. Neither galantamine nor donepezil negatively affected sleep; however, on every measure, there were suggestions of slightly more benefit associated with galantamine treatment. Although these results are suggestive of a differential effect of the drugs on sleep, further research is needed to confirm the clinical significance.

Undertreatment of patients with Alzheimer's disease in an elderly United States population.

BACKGROUND: The aim of this study was to assess the undertreatment of elderly mild to moderate Alzheimer's disease (AD) patients in the United States utilizing baseline data from a community-based trial that has established comparability to national survey samples on demographic characteristics. METHODS: Baseline data were used from an open-label, 12-week, postapproval study of compliance with galantamine, an AChEI and nicotinic receptor modulator, and vitamin E. A total of 2,114 patients from 406 community-based US practices in which physicians had previously treated patients with acetylcholinesterase inhibitors (AChEIs) were included in the study. This population reflects a large, ethnically diverse patient pool consistent with the demographics of the elderly population in the United States, atypical of those enrolled in most AD trials. RESULTS: The majority of patients (64.5%) were described by either themselves or their caregivers as not having received prior AChEI treatment. Positive associations were found between past AChEI treatment and longer time since diagnosis, white race, higher education, medical care by a neurologist, and older caregivers. The likelihood of having received previous AChEI treatment was higher among white patients (61.9%) than among those from other ethnic groups combined (25.8%). CONCLUSIONS: The similarity of patient demographic characteristics to the 2000 US Census figures for the population aged >65 years makes this data set a potentially powerful tool for planning public health initiatives. Findings suggest that patients with mild to moderate AD are undertreated and that specialist and nonspecialist organizations should discuss and implement ways to optimize management of this disease.

Tools for diagnosing migraine and measuring its severity.

Migraine remains substantially underdiagnosed and undertreated in the United States. Tools to screen for migraine and to measure headache-related disability can help address barriers to effective diagnosis and treatment. In this article, public health criteria for screening programs for any medical condition are first reviewed. Modifications of these criteria for migraine and other chronic/episodic disorders are then proposed. Migraine is assessed to determine how well it meets criteria for screening and the steps that are necessary before firm public policy recommendations for screening for migraine are possible.