The misuse and abuse of these forms of restraint were major antecedents for the sweeping nursing home reform enacted in 1987. The Omnibus Budget Reconciliation Act’s (OBRA) Nursing Home Reform Act led to federal regulations requiring preadmission screening for mental disorders, prohibiting the inappropriate (eg, for discipline) use of restraints, and creating specific indications and guidelines for the use of antipsychotics.13-15 In general, studies have shown that the OBRA regulations had the intended effect on antipsychotic medication use: a substantial decrease in use without a signif-icant concomitant increase in the use of other medications.13,16
Antipsychotics for neuropsychiatric symptoms of dementia?
It was long believed that atypical antipsychotics were the drugs of choice for the treatment of behavioral disturbances in dementia. Thus, clinicians faced with patients with difficult behavioral problems and no FDA-approved treatments often used these medications as first-line treatment.
In aggregate, atypical antipsychotics appear to have moderate efficacy in treating the neuropsychiatric symptoms of Alzheimer dementia, although several studies have not found their effects to be significantly different from those of placebo.17-19 In a meta-analysis of 15 randomized controlled trials of atypical antipsychotics in which psychosis and/or agitation in dementia were outcome measures, global assessments of neuropsychiatric symptom status improved only in a pooled analysis for risperidone(Drug information on risperidone) and aripiprazole(Drug information on aripiprazole).17 Scores specifically related to psychosis improved only in trials using risperidone.17 Full interpretation of these data is difficult, because these trials were done in a variety of settings using a variety of outcomes measures.
The recent Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer Disease (CATIE-AD) attempted to assess the effectiveness of atypical antipsychotics for the treatment of psychosis or agitation in dementia, with a seemingly more relevant outcome in the initial phase of the trial: time to discontinuation for any reason. Patients were randomized to olanzapine(Drug information on olanzapine), quetiapine(Drug information on quetiapine), risperidone, or placebo. Interestingly, the atypical antipsychotics did not prove to be superior to placebo on the primary (time to discontinuation for any reason) or secondary (Clinical Global Impression scale) outcome measure at 12 weeks.20
Although the trial was designed to answer the question of efficacy, there are a number of interesting issues. For example, patients in the placebo arm most often switched because of lack of efficacy, whereas those in the various treatment arms had higher switching rates because of adverse effects. However, the drugs that patients were switched to and often continued had similar rates of adverse effects. This suggests that there are some medications that do show efficacy for some patients, and that for them, adverse effects were considered tolerable in light of efficacy. In addition, the primary outcome measure was time to discontinuation (including switching drugs), and clinicians knew that only the first phase of the trial included a placebo arm. Thus, in the first phase, the rate of switching drugs may have been higher than that of adjusting the dosage.
Results of studies suggest a differential pattern of response to antipsychotics. Schneider and colleagues17found a better global neuropsychiatric response in patients without psychosis, which suggests that atypical antipsychotics may be more efficacious in patients with agitation alone. Although some randomized controlled trials seemed to show a modest effect in treating aggressive behavior and agitation, others did not. The atypical antipsychotics that were reported to have some efficacy included risperidone, olanzapine, and aripiprazole.17
Although the adverse-effect profile of older, conventional (typical) antipsychotics has discouraged many clinicians from using them, they remain widely used in elderly patients with dementia. However, when typical antipsychotics were compared with atypical antipsychotics in 4 randomized controlled trials, there was no evidence to suggest that conventional agents were better at treating psychotic or behavioral symptoms in Alzheimer disease.21-24 Three of these studies compared risperidone with haloperidol(Drug information on haloperidol), and 1 study compared quetiapine with haloperidol. While there is no proven advantage in efficacy for atypicals, conventional antipsychotics are well known to carry greater risk of extrapyramidal symptoms, such as tremor and rigidity, akathisia, and tardive dyskinesia, particularly in elderly populations.