olanzapine and Cerebrovascular-Disorders

The objective of the present study is to systematically review the supporting evidence for the use of antipsychotics in the treatment of behavioral and psychological symptoms in patients with dementia, as well as the controversies and limitations of this prescription. We discuss the available evidence in the light of the high prevalence of behavioral and psychological symptoms of dementia in this population, along with the greater susceptibility of elderly patients to adverse events.. Systematic literature review of the use of typical and atypical antipsychotics in patients with dementia was carried out in the databases PubMed/Medline, Embase and SciELO. The search was limited to clinical trials and meta-analysis of the literature published from 1986 to 2007.. Evidence drawn from randomized, double-blind, placebo controlled trials support the use of both typical and atypical antipsychotics in the treatment of behavioral symptoms of dementia, especially psychotic symptoms and abnormal psychomotor activity. Nevertheless, the use of these drugs in demented patients is not devoid of important adverse events. Although the induction of extrapyramidal symptoms is not as frequent or severe with atypical antipsychotics as it is with first-generation neuroleptics, the former drugs may particularly increase the risk of cerebrovascular events and death.. Although effective, antipsychotic drugs must be prescribed cautiously in patients with dementia. Dose regimens, duration of treatment and a cautious assessment of risk-benefit must be established for each patient.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cerebrovascular Disorders; Dementia; Dementia, Vascular; Dibenzothiazepines; Double-Blind Method; Evidence-Based Medicine; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

To examine whether cerebrovascular risk, executive function, and processing speed are associated with acute treatment outcome of psychotic depression in older adults.. The authors analyzed data from 142 persons aged 60 years or older with major depression with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo. The independent variables were baseline cerebrovascular risk (Framingham Stroke Risk Score), baseline executive function (Stroop interference score and the initiation/perseveration subscale of the Mattis Dementia Rating Scale), and baseline processing speed (color and word reading components of the Stroop). The outcome variable was change in severity of depression, measured by the 17-item Hamilton Depression Rating Scale total score, during the course of the RCT.. Greater baseline cerebrovascular risk was significantly associated with less improvement in depression severity over time, after controlling for pertinent covariates. Neither executive function nor processing speed predicted outcome.. This study suggests an association of cerebrovascular risk, but not executive function or processing speed, with treatment outcome of major depression with psychotic features in older adults.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cognition; Cognition Disorders; Depressive Disorder, Major; Double-Blind Method; Executive Function; Humans; Mental Processes; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Reaction Time; Risk; Sertraline; Severity of Illness Index; Stroop Test; Treatment Outcome; Young Adult

In March 2004, the UK Committee of Safety of Medicines (CSM) informed clinicians that risperidone and olanzapine should not be used to treat behavioural and psychological symptoms of dementia (BPSD) because of increased risk of strokes with both drugs and increased risk of mortality with olanzapine. An audit to examine the implications of the implementation of the CSM guidance was undertaken.. All patients receiving these two drugs, in one psychogeriatric service, at the time of CSM guidance were identified and reviewed. Data on clinical and demographic features, patient and carer involvement in the review and clinical outcome of the efficacy of the overall treatment package at 6 month follow-up was ascertained from the case-notes.. The main findings were: (i) all patients receiving risperidone or olanzapine were identified and reviewed at a median interval of 8 days after the CSM guidance; (ii) most patients and carers were involved in the initial review; (iii) risperidone and olanzapine were discontinued in 22 and 12 of the patients respectively, and in 19 of these patients another neuroleptic was substituted; (iv) there was no relationship between discontinuation of these two drugs and presence of cerebrovascular and cardiovascular risk factors; and, (v) there was no relationship between the clinical outcome of efficacy at six months and discontinuation of these two drugs.. This study illustrates that it is possible to identify, review and follow-up patients on these two drugs and involve the patient and carer in the review, and clinical outcome of efficacy of the overall treatment package is not adversely affected by continuation or discontinuation of these two drugs.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Cerebrovascular Disorders; Dementia; Drug Administration Schedule; Female; Humans; Male; Medical Audit; Olanzapine; Practice Guidelines as Topic; Risk Factors; Risperidone; Treatment Outcome; Withholding Treatment

As clinicians we talk about "the best interests of our patients". How can a treatment which doubles the rate of cognitive decline, triples the rate of stroke, doubles mortality, substantially increases falls and fractures and reduces quality of life be beneficial, especially, as in real life, once neuroleptics are started they are rarely discontinued with cumulative adverse effects? As there is clearly no rational reason for prescribing, we need to consider other explanations. We would suggest the following: Therapeutic impotence: Doctors, especially specialists feel they need to do something, and prescribing a familiar drug is the easiest option. Ignorance: Doctors are either unaware of the substantial evidence of harm with neuroleptics or are swayed by slick marketing information, portraying atypical neuroleptics in an "over-safe" light that does not reflect the actual data. Placebo effect: If neuroleptics are prescribed, the majority of patients experience an improvement in BPSD symptoms. This reinforces the apparent value of this practice, as we like to take the credit for any improvements that occur. The reality is that the majority of people would have experienced a comparable improvement with monitoring. Bowing to pressure: Sometimes the pressure to respond can be great, and a prescription is an easy way to relieve the pressure. This is understandable, and reflects a similar phenomenon to that of general practioners prescribing antibiotics for sore throats. In neither situation does it represent good practice. Lack of skills to implement non-pharmacological alternatives: The main evidence for alternative treatment options are for therapies that by and large are not a core part of the physician or psychiatrist's skill-base, such as psychological interventions. Doctors therefore feel uncomfortable pursuing these options. Why for example is so little time spent on the nonpharmacological interventions that everyone agrees should be the first line of treatment for BPSD in people with dementia? It is largely assumed that the "enlightened clinician has already appropriately assessed and diagnosed the patient and exhausted all the possible environmental and behavioral interventions before resorting to the prescription pad." Accumulating evidence clearly indicates that the need for psychotropic medication is substantially reduced by proactive services or interventions which can provide training and promote psychological, social and environmental and sensory

Topics: Accidental Falls; Aged; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cognition; Dementia; Humans; Mental Disorders; Olanzapine; Quality of Life; Risperidone

Concern exists about a possible increased risk of cerebrovascular events (CVEs) among elderly patients receiving risperidone or olanzapine. We estimated the effect of atypical and conventional antipsychotics on the risk of CVEs among elderly nursing home patients with dementia.. We conducted a case-control study on residents of nursing homes in 6 U.S. states by using the Systematic Assessment of Geriatric drug use via Epidemiology database, which includes data from the Minimum Data Set linked to Medicare inpatient claims. Participants were diagnosed with Alzheimer's disease or other forms of dementia on the basis of clinical criteria and medical history (including medical records and neuroradiologic documentation). Cases included patients hospitalized for stroke or transient ischemic attack between June 30, 1998, and December 27, 1999. For each case, we identified up to 5 controls hospitalized for septicemia or urinary tract infection residing in the same facility during the same time period. The sample consisted of 1130 cases and 3658 controls.. After controlling for potential confounders, the odds ratio of being hospitalized for CVEs was 0.87 (95% CI = 0.67 to 1.12) for risperidone users, 1.32 (95% CI = 0.83 to 2.11) for olanzapine users, 1.57 (95% CI = 0.65 to 3.82) for users of other atypical agents, and 1.24 (95% CI = 0.95 to 1.63) for conventional antipsychotic users compared to nonusers of antipsychotics. A history of CVEs appeared to modify the effect of atypical antipsychotics other than risperidone on the risk of new events.. Overall, no increased risk of CVEs seems to be conferred by atypical or conventional antipsychotics. Preexisting cerebrovascular risk factors might interact with some atypical antipsychotics to increase the risk of events. These results should be interpreted in light of the limitations of the study and need to be confirmed.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cerebrovascular Disorders; Clozapine; Comorbidity; Dementia; Female; Geriatric Assessment; Hospitalization; Humans; Ischemic Attack, Transient; Male; Medical Records Systems, Computerized; Nursing Homes; Odds Ratio; Olanzapine; Risk Factors; Stroke; United States

The possibility that low-dose antipsychotic treatment is associated with increased risk of cerebrovascular events (CVEs) in elderly patients with dementia has been raised. The objective was to determine whether risperidone is associated with an increased risk of CVEs relative to other commonly considered alternative treatments.. An analysis of Medicaid data from 1999 to 2002, representing approximately 8 million enrollees from multiple states, was conducted. The primary outcome was the incidence of acute inpatient admission for a CVE within 3 months following initiation of treatment with atypical antipsychotics (risperidone, olanzapine, quetiapine, or ziprasidone), haloperidol, or benzo-diazepines.. Descriptive analyses found similar rates of incident CVEs across evaluated agents. Multivariate analyses found no differences in comparisons of risperidone with olanzapine or quetiapine. Risperidone and other antipsychotics as a group were also not associated with a higher odds ratio (OR) of incident CVE than either haloperidol or benzodiazepines. With risperidone as the reference group: olanzapine, OR = 1.05, 95% CI 0.63-1.73; quetiapine, OR = 0.66, 95% CI 0.23-1.87; haloperidol, OR = 1.91, 95% CI 1.02-3.60; benzodiazepines, OR = 1.97, 95% CI 1.30-2.98. With benzodiazepines as the reference group, the OR of incident CVE for all antipsychotics as a class was 0.49, 95%CI 0.35-0.69.. This study found no significant difference in the incidence of CVEs between patients taking risperidone and those taking other atypical antipsychotics. Risperidone and all atypical antipsychotics were not associated with higher risk than two common treatment alternatives (haloperidol and benzodiazepines). These findings do not support the conclusion that risperidone is associated with a higher risk of CVE than other available treatment alternatives. The data also suggest that patient characteristics other than antipsychotic use are more significant predictors of CVEs. Given the relatively low rates of incident CVEs, a larger sample of patients with groups closely balanced on a wide spectrum of potential risk factors could provide a more precise assessment of risk.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cohort Studies; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Haloperidol; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Patient Admission; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Thiazoles

Topics: Adverse Drug Reaction Reporting Systems; Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Clinical Trials as Topic; Contraindications; Humans; Olanzapine; Product Surveillance, Postmarketing