Joan Mackell

Obesity as a risk factor for antipsychotic noncompliance

Abstract Objective: Weight gain is a common side effect of antipsychotic medications and is of particular concern with most of the newer “atypical” antipsychotics. It is, therefore, increasingly important to understand the impact of obesity and perceived weight problems on compliance with these medications. Methods: A survey of treatment and health issues was mailed to local chapters of the National Alliance for the Mentally Ill (NAMI) and National Mental Health Association (NMHA), who distributed them to people with schizophrenia. Noncompliance was defined as a self-report of missing any antipsychotic medication in the previous month. The primary independent variables were (1) body mass index (BMI; weight [kg]/height [m2])—categorized as normal ( 30, n=100)—and (2) subjective distress over weight gain. Other independent variables included demographics, medication attitudes, and treatment satisfaction. Result: BMI status and subjective distress from weight gain were predictors of noncompliance. Obese individuals were more than twice as likely as those with a normal BMI to report missing their medication (OR=2.5; CI 1.1–5.5). A comprehensive model suggested that the primary mediator of noncompliance was distress over weight gain. Conclusions: There appears to be a significant, positive association between obesity and subjective distress from weight gain and medication noncompliance, even when accounting for other possible confounding factors.

The Severe Impairment Battery: Concurrent Validity and the Assessment of Longitudinal Change in Alzheimer's Disease

Measurement of cognitive dysfunction in the early stages of Alzheimers disease (AD) has been well studied and there are many objective tests in use for this purpose. However, with the exception of clinical rating scales, such as the Clinical Dementia Rating Scale, Global Deterioration Scale, and Functional Assessment Staging, there are few objective measures of cognition in the more advanced stages of AD. Given a renewed interest in potential AD therapies, objective measures of mental functioning are needed to adequately assess change in more advanced AD patients. As part of an effort by the NIA-Alzheimers Disease Cooperative Study to evaluate new measures of efficacy for their utility in treatment studies, the Severe Impairment Battery (SIB) was examined in a 1-year evaluation of change across a wide range of AD severity. The data suggest that the SIB is a reliable and valid measure of progression, particularly in persons with moderate to severe AD. The SIB may therefore be a useful outcome measure in clinical trials that include patients with more advanced stages of AD.

The Economic Impact of Migraine: An Analysis of Direct and Indirect Costs

Objective.—This study examined whether individuals with migraine incurred greater direct and indirect costs than a matched group free of migraines.

Bodyweight gain associated with atypical antipsychotics: epidemiology and therapeutic implications.

Atypical antipsychotic medications are associated with different adverse effects and efficacy profiles compared with conventional antipsychotics (i.e. less extrapyramidal symptoms, improved efficacy against negative symptoms and cognitive deficits, and most often a greater ability to improve patients’ quality of life). However, the atypical antipsychotics may be associated with clinically significant bodyweight gain, increasing the risk of medical comorbidity, including diabetes mellitus, hypertension, cardiovascular disease and hyperlipidaemia.This literature review assesses the various bodyweight gain liabilities associated with atypical antipsychotics, as well as the effects of bodyweight gain on quality of life. The issue of prevention and management of this often neglected adverse effect is also examined.Most studies reviewed indicate that clozapine and olanzapine are associated with more bodyweight gain than the other atypical antipsychotics. There are potential factors that place certain patients at greater risk for bodyweight gain, including low pretreatment body mass index, young age and being of female gender. Furthermore, bodyweight gain associated with the use of atypical anti-psychotics has been reported to be associated with clinical improvement, although this has not been substantiated widely. It is unclear whether increased medical comorbidity, including diabetes mellitus, coronary artery disease and/or elevated triglyceride levels, is secondary to the bodyweight gain associated with atypical antipsychotics, or the result of the agents themselves.A patient’s quality of life may be greatly affected by excessive bodyweight gain; either by increased comorbid medical illness, an increased relapse rate associated with noncompliance, or the social stigma associated with being obese. However, most studies reveal that treatment with atypical antipsychotic medications is associated with improved quality of life compared with that achieved with conventional antipsychotic medications.Because bodyweight is an important health risk associated with atypical antipsychotics, prevention and effective management of bodyweight are paramount in preventing comorbid medical illness, relapse and possible noncompliance.

Behavioral effects of current Alzheimer's disease treatments: A descriptive review

Behavioral abnormalities and neuropsychiatric symptoms are common manifestations of Alzheimers disease (AD). Many clinical trials of cholinesterase inhibitors (ChE‐Is) and memantine have included behavioral measures as primary or secondary outcomes, and most have observed behavioral benefits in conjunction with treatment. The purpose of this review was to determine the frequency of positive behavioral outcomes in AD clinical trials and clinical reports, to determine the symptoms most responsive to antidementia agents, and to explore factors that correlate with negative outcomes in clinical trials of antidementia agents with regard to behavioral measures.

A multicenter evaluation of new treatment efficacy instruments for Alzheimer's disease clinical trials : Overview and general results

Evaluating treatment efficacy in Alzheimers disease (AD) clinical trials requires optimal assessment methods to determine the extent and clinical meaningful-ness of potential therapeutic effects of pharmacologic agents. Development of improved outcome measures for AD clinical trials is a major objective of the Alzheimers Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS Instrument Development Project evaluated the sensitivity, reliability and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. A total of 306 English-speaking subjects were enrolled in the study, including AD patients stratified by disease severity and cognitively normal, age-matched elderly subjects. Half were retested at 1 month and 2 months after baseline, and all received 6-and 12-month follow-up assessments. Spanish versions of these new measures are currently being evaluated. The development of this multisite study, the common methods and procedures, and a detailed description of the cohort are provided in this overview article. This multisite project demonstrates the feasibility of a consortium approach to instrument development. We were able to develop new instruments and efficiently evaluate their reliability and sensitivity to longitudinal change by capitalizing on the experience and patient resources of the participating ADCS research sites.

A longitudinal study of behavioral pathology across five levels of dementia severity in Alzheimer's disease: The CERAD behavior rating scale for dementia

As part of the Alzheimers Disease Cooperative Study (ADCS) Instrument Development Project, the CERAD Behavior Rating Scale for Dementia (BRSD) was examined for its sensitivity to degree of cognitive impairment, its test-retest reliability, and its sensitivity to longitudinal change. Sixty-four normal elderly participants and 261 patients with AD stratified into severity groups based on Mini-Mental State Exam (MMSE) scores were rated on the BRSD at baseline and 12-month follow-up visits. A subset of subjects was evaluated at a 1-month follow-up visit. Baseline BRSD Total Score discriminated the normal group from each AD group, and mean Total Score significantly increased with increasing dementia severity. Test-retest reliability between baseline and 1-month Total Scores was satisfactory for all AD groups. Longitudinal change was evaluated by 12-month change scores, which were significant in only the normal and in one AD group. From the results, we argue that the value of behavioral pathology assessment in clinical trials would be enhanced if additive scores were based on groups of correlated items rather than on a broad array of behaviors, some of which may increase and others may decrease in frequency as AD progresses.

Effect of donepezil on emergence of apathy in mild to moderate Alzheimer's disease

To determine whether donepezil treatment (10 mg/day over 24 weeks) is associated with delayed emergence of apathy in patients with mild to moderate Alzheimers disease (AD) and to explore relationships between donepezils effects on apathy and other Neuropsychiatric Inventory (NPI)–measured behavioural symptoms.

Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain

Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

Efficacy and safety of donepezil 23 mg versus donepezil 10 mg for moderate-to-severe Alzheimer's disease: a subgroup analysis in patients already taking or not taking concomitant memantine.

Background/Aims: A large multicenter trial of donepezil 23 mg/day versus donepezil 10 mg/day for moderate-to-severe Alzheimer’s disease allowed patients taking concomitant memantine. We evaluated the efficacy/safety of donepezil 23 and 10 mg/day in this trial, with respect to concomitant memantine use. Methods: Prespecified analysis of data from a 24-week, randomized, double-blind trial. Patients were randomized to donepezil doses (23 vs. 10 mg/day) and stratified by concomitant memantine use (yes or no). Efficacy and safety were assessed for each donepezil dose in subgroups taking or not taking concomitant memantine. Results: At week 24, donepezil 23 mg/day provided significant cognitive benefits over 10 mg/day (p < 0.01) on the Severe Impairment Battery, with or without concomitant memantine (ANCOVA adjusted for baseline score, country and treatment). The higher dose showed no benefit on the global function, Mini-Mental State Examination or activities of daily living measures in either memantine subgroup. Rates of treatment-emergent adverse events (AEs) were higher for donepezil 23 mg/day with memantine (80.7%) than 23 mg/day without memantine (69.7%) or 10 mg/day with/without memantine (66.7/62.0%); across all treatment groups, most events were mild/moderate in severity. Individual rates of serious AEs were low (<1.0%), regardless of concomitant memantine use. Conclusion: In this population, concomitant memantine use did not alter the response profile of donepezil 23 vs. 10 mg/day. Donepezil 23 mg was generally safe and well tolerated among patients receiving donepezil alone and among patients receiving a combination of donepezil and memantine therapy.