olanzapine and Stroke

 To evaluate the frequency, validity, and relevance of statistically significant (P<0.05) sex-treatment interactions in randomized controlled trials in Cochrane meta-analyses..  Meta-epidemiological study..  Cochrane Database of Systematic Reviews (CDSR) and PubMed..  Reviews published in the CDSR with sex-treatment subgroup analyses in the forest plots, using data from randomized controlled trials..  Information on the study design and sex subgroup data were extracted from reviews and forest plots that met inclusion criteria. For each statistically significant sex-treatment interaction, the potential for biological plausibility and clinical significance was considered..  Among the 41 reviews with relevant data, there were 109 separate treatment-outcome analyses ("topics"). Among the 109 topics, eight (7%) had a statistically significant sex-treatment interaction. The 109 topics included 311 randomized controlled trials (162 with both sexes, 46 with males only, 103 with females only). Of the 162 individual randomized controlled trials that included both sexes, 15 (9%) had a statistically significant sex-treatment interaction. Of four topics where the first published randomized controlled trial had a statistically significant sex-treatment interaction, no meta-analyses that included other randomized controlled trials retained the statistical significance and no meta-analyses showed statistical significance when data from the first published randomized controlled trial were excluded. Of the eight statistically significant sex-treatment interactions from the overall analyses, only three were discussed by the CDSR reviewers for a potential impact on different clinical management for males compared with females. None of these topics had a sex-treatment interaction that influenced treatment recommendations in recent guidelines. UpToDate, an online physician-authored clinical decision support resource, suggested differential management of men and women for one of these sex-treatment interactions..  Statistically significant sex-treatment interactions are only slightly more frequent than what would be expected by chance and there is little evidence of subsequent corroboration or clinical relevance of sex-treatment interactions.

Topics: Benzodiazepines; Bias; Carotid Stenosis; Endarterectomy, Carotid; Female; Humans; Hyperprolactinemia; Incidence; Lung Neoplasms; Male; Olanzapine; Outcome Assessment, Health Care; Prolactin; Randomized Controlled Trials as Topic; Risperidone; Sex Factors; Stroke

Post hoc analyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients.

Topics: Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Dementia; Humans; MEDLINE; Olanzapine; Randomized Controlled Trials as Topic; Risk Factors; Risperidone; Stroke; Treatment Outcome

Post-hoc analysis by the pharmaceutical company Eli Lilly of 5 randomised clinical trials concerning the efficacy ofolanzapine in patients with dementia, has shown that patients taking olanzapine have a risk of experiencing a cerebrovascular accident which is 3 times higher than patients taking placebo. This increased risk has also been found in patients with dementia who take risperidone. Details concerning this relationship cannot be obtained from the sparse information supplied by the producers of risperidone and olanzapine. The pathophysiological mechanisms by which atypical antipsychotics may lead to cerebrovascular accidents are not well understood. Atypical antipsychotics are often prescribed for conditions in which evidence of the efficacy of this group of medications is lacking. This association between antipsychotics and cerebrovascular accidents emphasises the need for a stricter and evidence-based prescription policy for antipsychotics. In cases of adverse drug reaction, more openness on the part of pharmaceutical companies is desirable.

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Randomized Controlled Trials as Topic; Risk Factors; Risperidone; Stroke

Strong concerns have been raised about whether the risk of ischemic stroke differs between conventional antipsychotics (CAPs) and atypical antipsychotics (AAPs). This study compared the risk of ischemic stroke in elderly patients taking CAPs and AAPs.. We conducted a retrospective cohort study of 71,584 elderly patients who were newly prescribed the CAPs (haloperidol or chlorpromazine) and those prescribed the AAPs (risperidone, quetiapine, or olanzapine). We used the National Claims Database from the Health Insurance Review and Assessment Service (HIRA) from January 1, 2006 to December 31, 2009. Incident cases for ischemic stroke (ICD-10, I63) were identified. The hazard ratios (HR) for AAPs, CAPs, and for each antipsychotic were calculated using multivariable Cox regression models, with risperidone as a reference.. Among a total of 71,584 patients, 24,668 patients were on risperidone, 15,860 patients on quetiapine, 3,888 patients on olanzapine, 19,564 patients on haloperidol, and 7,604 patients on chlorpromazine. A substantially higher risk was observed with chlorpromazine (HR = 3.47, 95% CI, 1.97-5.38), which was followed by haloperidol (HR = 2.43, 95% CI, 1.18-3.14), quetiapine (HR = 1.23, 95% CI, 0.78-2.12), and olanzapine (HR = 1.12, 95% CI, 0.59-2.75). Patients who were prescribed chlorpromazine for longer than 150 days showed a higher risk (HR = 3.60, 95% CI, 1.83-6.02) than those who took it for a shorter period of time.. A much greater risk of ischemic stroke was observed in patients who used chlorpromazine and haloperidol compared to risperidone. The evidence suggested that there is a strong need to exercise caution while prescribing these agents to the elderly in light of severe adverse events with atypical antipsychotics.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Cohort Studies; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; Male; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Republic of Korea; Retrospective Studies; Risk; Stroke; Time Factors

We conducted a case-crossover study to evaluate the comparative risk of ischemic stroke associated with the use of risperidone, quetiapine and olanzapine in geriatric patients using the Korean Health Insurance Review and Assessment Service database. Cases included elderly patients >64 years old who had experienced their first ischemic stroke (International Classification of Disease, Tenth Revision (ICD-10), I63) hospitalization from July 2005 to June 2006 and who had been without prior cerebrovascular diseases (ICD-10, I60-I69), or transient ischemic attack (ICD-10, G45). Exposures to risperidone, quetiapine and olanzapine were assessed during the 30 days prior to the stroke episode. We set two control periods with lengths which were the same as the hazard periods. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated by conditional logistic regression. A total of 1601 cases of ischemic stroke with a mean age of 75.6 (±6.7) years were identified, among which 933 (58.3%) were female. An increased risk of ischemic stroke was associated with the use of risperidone (aOR=3.5, 95% CI 3.3-4.6) and quetiapine (aOR=2.7, 95% CI 2.0-3.6) during the 30 days prior to stroke: however, no significant risk was observed with olanzapine (aOR=1.2, 95% CI 0.7-2.0). The increased stroke risk in demented patients, assessed within 30 days after exposure, was also observed with olanzapine. However, the sample of olanzapine users was small and underpowered.

Topics: Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Confidence Intervals; Cross-Over Studies; Dibenzothiazepines; Humans; Middle Aged; Odds Ratio; Olanzapine; Quetiapine Fumarate; Risk; Risperidone; Stroke

Antipsychotic medication is often prescribed to persons with dementia exhibiting behavioural and psychological symptoms (BPSD). Use of atypical antipsychotics in elderly persons with dementia is associated with an increased risk of serious cerebrovascular adverse events and increased mortality. Based on a review of available literature, we conclude that atypical antipsychotics have a modest effect on BPSD and potentially serious side effects and that conventional antipsychotics appear to have even less favourable effects and adverse event profiles. Antipsychotic medication in patients with dementia exhibiting BPSD should only be prescribed for short-term treatment of severe symptoms associated with considerable distress or serious risk. Non-pharmacological interventions should be the first-line treatment approach in most cases.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dementia; Haloperidol; Humans; Methotrimeprazine; Middle Aged; Olanzapine; Risk Factors; Risperidone; Stroke

Topics: Administration, Oral; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Clozapine; Databases, Factual; Dementia; Dibenzothiazepines; Drug Utilization Review; Health Services for the Aged; Humans; Olanzapine; Pharmaceutical Services; Piperazines; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Stroke; Thiazoles; Treatment Outcome

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cause of Death; Controlled Clinical Trials as Topic; Dementia, Vascular; Humans; Olanzapine; Psychotic Disorders; Risk; Risperidone; Statistics as Topic; Stroke; Survival Analysis

Hemiballismus is a rare movement disorder characterized by involuntary, large amplitude movements of the limbs of 1 side of the body. We describe the case of a man in his late sixties with slurred speech, agitation, and right-sided hemiballismus resulting from a left thalamic hemorrhagic stroke. Treatment with haloperidol was unsuccessful, but both the hemiballismus and agitation diminished significantly after initiation of olanzapine (Zyprexa). The improvement in the hemiballismus was quantified by recording the number of hemiballistic movements that occurred while the patient performed standardized 30-minute sessions (daily for 5d). With the first task (reaching within the base of support while seated), the average number of hemiballismic movements per session decreased from a baseline of 23.5 to 3.0 in the upper extremity and from 20.5 to 7.0 in the lower extremity. With the second task (catching a ball while seated), the abnormal movements decreased from 52 to 6.3 in the upper extremity and from 34.5 to 2.7 in the lower extremity. This case suggests that olanzapine may be a valuable pharmacologic alternative for patients with hemiballismus.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dyskinesias; Humans; Male; Olanzapine; Stroke; Stroke Rehabilitation

Behavioral problems produce excess disability, potentially devastating in cognitively impaired patients. These behavioral symptoms can be a major cause of stress, anxiety and concern for caregivers. While psychotropic drugs are frequently used to control these symptoms, they have the potential for significant side effects, which include sedation, disinhibition, depression, falls, incontinence, parkinsonism and akathisia. We followed up (for 12 months) a group of 346 consecutive outpatients, with a diagnosis of subcortical vascular dementia or multi-infarctual dementia. Patients eligible for this open-label study were required to have behavioral problems (BPSD). Patients were divided into two groups, Group A received olanzapine 2.5-7.5 mg/day while Group B received typical antipsychotics. Patients in both groups were allowed to continue any previous therapy. Patients in both groups were significantly improved in their BPSD. Our patients had a host of medical conditions and received numerous concomitant medications. Given the potential complications associated with these therapeutic agents, these patients tolerated olanzapine quite well. On examination of consequences of adverse events, particularly somnolence, postural instability, and postural hypotension, it appeared that cerebrovascular events were not present. Moreover, no anticholinergic effect was recorded. These findings suggest that olanzapine could be a safe and effective treatment even for elderly population in suitable doses and receiving the adequate follow-up.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Dementia, Vascular; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Olanzapine; Randomized Controlled Trials as Topic; Risk Factors; Selective Serotonin Reuptake Inhibitors; Stroke; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Risk Factors; Risperidone; Stroke

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Risk Factors; Risperidone; Stroke

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Geriatric Psychiatry; Humans; Ischemic Attack, Transient; Mental Disorders; Olanzapine; Risperidone; Stroke; United States

Concern has been recently raised for risperidone and olanzapine, possibly associated with cerebrovascular events in placebo-controlled trials conducted in elderly subjects with dementia. We investigated the relationship between exposure to second-generation antipsychotics (SGAs) and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 or older with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 or older who received antipsychotic prescriptions during 2001. The 2 databases were linked anonymously using the individual patient code. The proportions of cerebrovascular accidents were 3.31% (95% confidence interval, 2.95-3.69) in elderly subjects exclusively exposed to SGAs and 2.37% (95% confidence interval, 2.19-2.57) in elderly subjects exclusively exposed to first-generation antipsychotics. After background group differences were controlled for, exposure to SGAs significantly increased the risk of accidents. The analysis of cerebrovascular events in elderly subjects exposed to each individual SGA, in comparison with exposure to haloperidol, showed a significantly increased risk for risperidone only (adjusted odds ratio, 1.43; 95% confidence interval, 1.12-1.93). These data provide preliminary epidemiological evidence that exposure to SGAs, in comparison with exposure to first-generation antipsychotics, significantly increased the risk of cerebrovascular accidents in the elderly.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Female; Haloperidol; Humans; Male; Odds Ratio; Olanzapine; Risperidone; Stroke

Following changes in the safety information on the use of risperidone and olanzapine in elderly patients with dementia, data from prescription-event monitoring (PEM) studies of risperidone, quetiapine and olanzapine were examined. The aim was to compare incidence rates for events reported as cerebrovascular accident (CVA) and transient ischaemic attack (TIA) during the first 180 days of treatment in patients prescribed atypical antipsychotics for dementia or other indications, because of the possible association between dementia and stroke in users of atypical antipsychotics. A retrospective analysis of data from the three observational studies was conducted using Poisson regression modelling and survival analysis. Within the risperidone, quetiapine and olanzapine cohorts, 23 (0.30%), 6 (0.35%) and 10 (0.11%) patients respectively, were reported to have had a CVA/TIA event. Age, sex and indication (dementia or other) were identified as important confounding variables; age being the most important. The crude rate ratios (RRs) for CVA/TIA for risperidone or quetiapine vs. olanzapine indicated an approximate threefold relative difference in rate during the first six months but after adjustment for age, sex and indication, the RRs were non-significant (1.2 (95% CI 0.5,3.0) and 2.1 (95% CI 0.6,7.7), respectively). For risperidone vs. quetiapine, crude and adjusted RRs were not significantly different. Of the three drugs, the time to event was shortest for risperidone and also shortest for risperidone or quetiapine users where the indication was dementia. The age and sex adjusted RR of CVA/TIA in patients prescribed risperidone for dementia vs. other indications was 6.7 (95% CI 2.4,18.9). The adjusted RRs for quetiapine, according to indication, could not be calculated due to missing information on age and sex. There were no cases of CVA/TIA with dementia for olanzapine, thus the RRs and time to event curves according to indication could not be examined. This study revealed no significant difference in the adjusted RR of CVA/TIA events in the first 180 days of treatment in patients prescribed risperidone or quetiapine when compared with olanzapine. However, dementia appears to be an important risk factor. These results should be considered alongside other pharmacoepidemiological studies on this topic.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Data Interpretation, Statistical; Dementia; Dibenzothiazepines; England; Family Practice; Female; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Olanzapine; Product Surveillance, Postmarketing; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Stroke; Survival Analysis; Time Factors; Treatment Outcome

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

Topics: Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Risk Factors; Risperidone; Stroke

Randomized controlled trials have suggested that at least one atypical antipsychotic may be associated with an increased risk of stroke in older people with dementia. This study examined the association between atypical antipsychotic use and stroke in the elderly.. The authors conducted a retrospective population-based cohort study of patients over the age of 66 by linking administrative health care databases. Three cohorts-users of typical antipsychotics, risperidone, and olanzapine-were identified and compared.. Subjects treated with typical antipsychotics (N=1,015) were compared with those given risperidone (N=6,964) and olanzapine (N=3,421). Model-based estimates adjusted for covariates hypothesized to be associated with stroke risk revealed relative risk estimates of 1.1 (95% CI=0.5-2.3) for olanzapine and 1.4 (95% CI=0.7-2.8) for risperidone.. Olanzapine and risperidone use were not associated with a statistically significant increased risk of stroke compared with typical antipsychotic use.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Comorbidity; Dementia; Female; Geriatric Assessment; Humans; Male; Olanzapine; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Risperidone; Stroke

Topics: Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dementia; Humans; Olanzapine; Risperidone; Stroke; Treatment Outcome; United Kingdom; United States