Antipsychotic Agents in Patients with Dementia (original) (raw)
Related papers
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2007
Dementia is a neuropsychiatric disorder characterized by cognitive impairment and behavioral and psychological symptoms. The efficacy and tolerability of risperidone for treating dementia-associated psychological and behavioral disturbances were evaluated in a study of 135 patients aged 60-85 years with DSM-IV diagnoses of Alzheimer's disease. All were treated with risperidone at a starting dose of 0.5 mg once daily at bedtime. After the first 3 days of therapy the dosage was increased to 1 mg in 2 doses (morning and evening), then a further 0.5 mg was added (alternatively in the morning and in the evening) every three days until attenuation of the psychiatric symptoms. The response to treatment was evaluated for a period of 12 weeks by the Neuropsychiatric Inventory (NPI) and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Both NPI and BEHAVE-AD were administered at the baseline visit, and after 4 and 12 weeks of therapy. Tolerability was assessed by the incidence of clinically evident side effects. The mean dose at endpoint was 1 mg/day of risperidone. The mean NPI score was 28.80+/-13.92 at start, 15.55+/-11.25 after 4 weeks and 8.30+/-7.00 at endpoint. The reduction in mean scores at 4 and 12 weeks was statistically significant in most of the Neuropsychiatric Inventory items, except for appetite disorders (p<0.0001). The mean BEHAVE-AD score was 20.44+/-3.92 at start, 13.50+/-11.39 after 4 weeks and 8.03+/-7.80 at endpoint. All the items showed a statistically significant improvement after 4 and 12 weeks (p<0.0001). The results were better at 12 than at 4 weeks. In our elderly patients with dementia low-dose risperidone was well tolerated and associated with reductions in BPSD, in particular agitation, aggression, irritability, delusions, sleep disorders, anxiety and phobias.
Journal of the American Geriatrics Society, 2000
, the Coronary Drug Project 1 showed that, in patients assigned to placebo, those that took the lactose pill 80% or more of the time had half the death rate of those who took the placebo less faithfully. The authors made no claim about the benefit of the placebo. Rather they emphasized the basic scientific observation that compliant patients are different from noncompliant ones. Recently, Geldmacher et al. 2 published similar findings. They showed that patients with Alzheimer's disease (AD) who took a pill of donepezil 80% or more of the time had a longer interval before nursing home placement (NHP) than those who took the donepezil less faithfully. These authors interpret their data differently from the Coronary Drug Project authors. They assert that, ''Use of donepezil by AD patients resulted in significant delays in NHP.'' Their claim is particularly implausible because of the enormous difference between caregivers who keep patients compliantly enrolled for years and those who do not. This difference in caregiver dedication and capacity will surely account for most, if not all, of the difference seen in rates of NHP. A placebo-controlled trial would, of course, be necessary to determine whether donepezil actually has any benefit whatsoever regarding NHP. The authors feel that such a study would be unethical though, ''Given that treatment with cholinesterase inhibitor (ChEI) is currently recommended as the standard of care for AD patients.'' As reference for this ethics claim, they cite the American Academy of Neurology Practice Parameter on Management of Dementia, but in doing so, they are regrettably misleading. Here is what the relevant guideline actually says, in its entirety: ''Pharmacologic treatment of AD. ChEI should be considered in patients with mild to moderate AD (Standard), although studies suggest a small average degree of benefit.'' 3 The authors conclude with the suggestion that we should think of treating AD with donepezil (yes, donepezil) in the same way we think of treating hypertension; ''years of treatment'' will be needed. In summary, this article, produced ''under the direction of, and with funding from Eisai Inc., and Pfizer Inc.,'' uses flimsy data to make an unjustifiable claim of ''results'' from donepezil. It misrepresents a key Practice Parameter to claim that generating useful data would be unethical. It recommends long-term use of the specific product, for many years of which, as with hypertension, no treatment benefit would be seen.
Efficacy of risperidone for treating patients with behavioral and psychological symptoms of dementia
International Psychogeriatrics, 2004
Background: Large randomized controlled trials have shown that risperidone reduces the frequency and severity of behavioral and psychological symptoms of dementia (BPSD) in patients with dementia. Since such trials are obliged to use very strict inclusion and exclusion criteria, their information about the efficacy is limited by the criteria used. Thus, the aim of the present study was to investigate the efficacy of risperidone on BPSD in a sample of patients routinely treated by their primary care physicians.Methods: A total of 938 elderly patients in Austria suffering from BPSD and routinely treated by their primary care physicians were included in this open-label prospective study. Patients received a flexible dose of risperidone, starting with 0.5 mg daily, for at least 6 weeks. Questionnaires were filled in before the start and after 6 weeks of treatment.Results: Before starting treatment with risperidone, BPSD were severe in 36.6% of the patients, moderate in 49.3%, and mild i...
Archives of Gerontology and Geriatrics, 2004
This double-blind study evaluated the efficacy and safety of risperidone or olanzapine vs. promazine in the treatment of behavioral and psychological symptoms in dementia (BPSD). Patients were required to be 65 years or older, to have DSM-IV diagnoses of Alzheimer's disease (AD), vascular dementia (VD) or a combination of both. A brain computerized tomography (CT) was performed for all the patients; 60 demented patients, 27 men (45 %) and 33 women (55 %) were selected for this study. The University of California Los Angeles neuropsychiatric inventory (NPI) was administered at baseline, then after 4 and 8 weeks. Patients had at least a score of 24 or more. The Hoehn and Yahr scale was used for evaluating parkinsonism. The scales were administered by an examinator who was not aware of the kind of treatment of the patients. After a wash-out period of 10 days, 20 patients, 9 men and 11 women, mean age 76.6 ± 6.0 years, were randomly assigned to risperidone 1 mg daily in divided doses (morning and bedtime) (Group A); 20 patients, 9 men and 11 women, mean age 82.5 ± 9.3 years were randomly assigned to olanzapine 5 mg at bedtime (Group B), and 20 patients, 9 men and 11 women, mean age 77.6 ± 4.6 years, were randomly assigned to promazine 50 mg daily (morning and bedtime) (Group C). In case of lack of clinical response, after 4 weeks, the dose could be increased to 2 mg/day of risperidone, 10 mg/day of olanzapine, and to 100 mg/day of promazine in the respective groups. Repeated measures ANOVA was used for the statistical analysis of rating scales over time (baseline, 4 and 8 weeks). At the end of the 8th week, a global improvement was obtained in 80% of patients treated with risperidone and olanzapine, vs. 65 % of patients treated with promazine (p < 0.01). The results show that risperidone in doses of 1-2 mg/day and olanzapine in doses of 5-10 mg/day are effective and safe in the treatment of BPSD. Risperidone presents a major and dose-dependent antidopaminergic action and seems to be preferable when hallucinations and delusions are prevailing symptoms, even if it gives good results on aggression and wandering. Olanzapine seems to be faster in its sedative effect, probably for H 1 receptor blockade. Moreover, 5-HT 6 antagonism may favor acethylcholine release and this explains why these patients have not presented a cognitive worsening. However, both drugs are comparable or even superior to promazine, with significantly fewer side effects of both anticholinergic and extrapyramidal character.
European Neuropsychopharmacology, 1997
Data on the clinical safety of risperidone from randomized clinical trials and postmarketing observations were reviewed. The most commonly reported non-extrapyramidal adverse events in 1,085 patients treated with risperidone in the clinical trials were insomnia (11.2%; in 6.3% of placebo controls), anxiety (8.9%; in 1.4% of placebo controls), and headache (5.6%; in 9.2% of placebo controls). All other adverse events occurred with an incidence of less than 5%. Information from postmarketing observations includes data on overall mortality, suicide, QTc prolongation, hematologic abnormalities, neuroleptic malignant syndrome, abnormal liver function test results, and overdose (defined as >32 mg). The incidence of these adverse events in patients treated with risperidone was less than the incidence found in epidemiological studies (when available). Worldwide experience with risperidone amounts to nearly 3.5 million patients, covering more than 1 million patient-years. Thus it is likely that all serious adverse events induced by risperidone that occur with an incidence of at least 1 in 1 million patients have been observed at least once. The observed adverse events during the 4-year postmarketing period are in line with the labelling for risperidone. It can be concluded that risperidone has an acceptable benefit/risk balance.
Use and safety of antipsychotics in behavioral disorders in elderly people with dementia
Journal of Clinical Psychopharmacology, 2014
In recent years, the use of antipsychotics has been widely debated for reasons concerning their safety in elderly patients affected with dementia. To update the use of antipsychotics in elderly demented people, a MEDLINE search was conducted using the following terms: elderly, conventional and atypical antipsychotics, adverse events, dementia, and behavioral and psychotic symptoms in dementia (BPSD). Owing to the large amounts of studies on antipsychotics, we mostly restricted the field of research to the last 10 years.
Use of atypical antipsychotic drugs in patients with dementia
American Family Physician, 2003
Typical antipsychotic drugs, such as haloperidol (Haldol), traditionally have been used to control psychotic and behavior disturbances in elderly patients, but these drugs have troubling side effects. Extrapyramidal symptoms can cause stiffness, immobility, and falls and are associated with significant mor-M ost family physicians are comfortable prescribing antidepressants, but antipsychotic medications are less commonly prescribed and therefore less familiar. Antipsychotic drugs effectively treat psychosis caused by a variety of conditions (Table 1). Psychotic symptoms are classified as either positive or negative. Positive symptoms include hallucinations, delusions, thought disorders (manifested by marked incoherence, derailment, tangentiality), and bizarre or disorganized behavior. Negative symptoms include anhedonia, flattened affect, apathy, and social withdrawal. 1 Psychotic symptoms in elderly patients always should be investigated thoroughly, and underlying medical conditions should be identified and treated. Although a family physician is less likely to manage schizophrenia in elderly patients, it is quite common for family physicians to treat patients who have Alzheimer's disease and Parkinson's disease. These patients frequently have psychotic symptoms that are treated without a specialist's aid. Increasingly, atypical antipsychotic drugs are prescribed for elderly patients with symptoms of psychosis and behavioral disturbances. These symptoms often occur in patients with Alzheimer's disease, other dementias, or Parkinson's disease. As the average age of Americans increases, the prevalence of Alzheimer's disease and Parkinson's disease will rise accordingly. Although nonpharmacologic treatments for behavioral disturbances should be tried first, medications often are needed to enable the patient to be adequately cared for. Current guidelines recommend using risperidone and olanzapine to treat psychosis in patients with Alzheimer's dementia. Quetiapine and clozapine are recommended for treatment of psychosis in patients with Parkinson's disease. Additional research is needed for a recently approved agent, ziprasidone. To minimize side effects, these medications should be started at low dosages that are increased incrementally. Drug interactions, especially those involving the cytochrome P450 system, must be considered. Clozapine's potentially lethal side effects limit its use in the primary care setting. Informed use of atypical antipsychotic drugs allows family physicians to greatly improve quality of life in elderly patients with dementia and behavior disturbances.
BMJ, 2004
Objective To review the role of oral atypical antipsychotic drugs in the management of the behavioural and psychological symptoms of dementia (BPSD). Data sources Medline, Embase, and the Cochrane Library. Reference lists were reviewed and experts were contacted to identify additional trials. Study selection Double blind randomised controlled trials that evaluated the four oral atypical antipsychotic therapies for BPSD. Review methods Two reviewers assessed trial validity independently. Data extraction Demographics of patients, study duration, dose of antipsychotic, primary end points, adverse events. Results 77 abstracts were reviewed. Five randomised trials (1570 patients) evaluating risperidone and olanzapine were identified. The quality of trials was generally good. Most participants were in an institution (> 96%), elderly (weighted mean 82.3 years), and had Alzheimer's disease (76.3%). Trials lasted 6-12 weeks. Treatment with atypical antipsychotic drugs was superior to placebo for the primary end point in three of the five trials. Two trials comparing risperidone with haloperidol did not find any differences in the primary measures of efficacy. Adverse events were common and included extrapyramidal symptoms, somnolence, and abnormal gait. Conclusions Although atypical antipsychotic drugs are being used with increasing frequency, few randomised trials have evaluated their use for BPSD. Limited evidence supports the perception of improved efficacy and adverse event profiles compared with typical antipsychotic drugs.
ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia
Neuropsychopharmacology, 2008
In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a metaanalysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6−1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a 'black box' warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.