Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study

Gill, Sudeep S.; Rochon, Paula A.; Herrmann, Nathan; Lee, Philip E.; Sykora, Kathy; Gunraj, Nadia; Normand, Sharon‐Lise T.; Gurwitz, Jerry H.; Marras, Connie; Wodchis, Walter P.; Mamdani, Muhammad

doi:10.1136/bmj.38330.470486.8f

Cited by 325 publications

(188 citation statements)

References 27 publications

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“…In 2004 the NMA warned against prescription of risperidone and olanzepine for elderly patients with dementia as published data showed a three-fold increase in cerebrovascular incidents in patients prescribed risperidone and olanzepine (Schneider et al, 2005;Brodaty et al, 2003). Later, a similar increased risk of cerebrovascular incidence has been demonstrated in typical antipsychotics as in atypical antipsychotics (Gill et al, 2005;Gill et al, 2007).…”

Section: Discontinuation Of Antipsychotic Medication and Npsmentioning

confidence: 73%

“…Newer atypical antipsychotics are believed to have fewer EPS than old typical antipsychotics, but atypical antipsychotics have been found to increase the risk of death and cerebrovascular disease in patients with dementia (Schneider et al, 2005;Ballard et al, 2011a). Cohort studies published thereafter indicated that typical antipsychotics might have even higher mortality rates than atypical antipsychotics (O'Brien, 2008;Gill et al, 2005;Gill et al, 2007). There are some indications of an association between agitation, aggression and psychosis in patients with dementia, which may have encouraged the use of antipsychotic medication for other NPS than psychosis in dementia (Rapoport et al, 2001).…”

Section: Antipsychotic Medicationmentioning

confidence: 99%

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Reliability and validity of the Norwegian version of the Severe Impairment Battery (SIB)

Bergh

Selbæk

Engedal

2008

Int J Geriat Psychiatry

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ObjectiveThe Severe Impairment Battery (SIB) is developed to test cognitive function in patients with dementia of moderate to severe degree. We have conducted a study to assess the inter‐rater reliability and the validity of the Norwegian version of SIB.MethodsThe reliability study comprised 30 patients, and the validity study 59 patients in nursing homes. We assessed Cronbach's alpha coefficient of the scale and the inter‐rater reliability for the total SIB score and its nine sub scores between two testers by means of the Spearman's correlation coefficients. In the validity study we compared the SIB scores with the scores on the Clinical Dementia Rating Scale.ResultsThe mean SIB score was 72.10 (SD 25.37). The Cronbach's alpha was 0.97, and the inter‐rater reliability of total SIB score was Spearman's rho 0.85, and ranged from 0.46 to 0.76 for the nine sub‐scores. The mean SIB score for patients with a CDR score < 2 was 84.2(13.4), whereas total scores for patients with CDR 2 and 3 were 74 (18.9) and 48.4 (33.3), respectively. A cut‐off point of 80.5 points gave the highest accuracy in discriminating between patients with CDR 2 and CDR 3, while a cut‐off point of 87.5 best discriminated between CDR < 2 and CDR 3.ConclusionThe study indicates that the Norwegian version of SIB is a reliable and valid test with which to evaluate the cognition in patients with dementia of moderate to severe degree. Copyright © 2008 John Wiley & Sons, Ltd.

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Section: Discontinuation Of Antipsychotic Medication and Npsmentioning

confidence: 73%

Section: Antipsychotic Medicationmentioning

confidence: 99%

Reliability and validity of the Norwegian version of the Severe Impairment Battery (SIB)

Bergh

Selbæk

Engedal

2008

Int J Geriat Psychiatry

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“…It is thus possible that some of the actual events could have been characterized as non-'cerebrovascular' in origin, although this does not mitigate concern about their seriousness. (c) Typical vs atypical antipsychotics: Gill et al (2005) in a retrospective cohort study reported that, after adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in the risk of ischemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.0, 95% CI 0.8, 1.3). This finding was consistent in subgroup analyses of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the total sample.…”

Section: Cerebrovascular Adverse Eventsmentioning

confidence: 99%

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

Jeste

Blazer

Casey

et al. 2007

Neuropsychopharmacol

329

273

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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 meta-analysis 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.

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“…The lack of placebo-controlled data with specific older conven-tional antipsychotics in patients with dementia cannot be interpreted as indicating that they are without similar risks. Three cohort studies have compared the risk of death or stoke in elderly patients (>65 years) treated with conventional antipsychotic versus atypical antipsychotics (Gill et al, 2005;Herrmann et al, 2004;Wang et al, 2005). Two studies found no significant difference in risk of stroke between the two groups (Gill et al, 2005;Herrmann et al, 2004) while the third found that conventional antipsychotics were associated with a significantly higher adjusted risk of death (Wang et al, 2005).…”

Section: Cerebrovascular Eventsmentioning

confidence: 99%

Neurological complications of psychiatric drugs: clinical features and management

Haddad

Dursun

2007

Hum. Psychopharmacol. Clin. Exp.

190

106

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This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyperreflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders.

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Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study

Abstract: Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics.

Cited by 325 publications

References 27 publications

Reliability and validity of the Norwegian version of the Severe Impairment Battery (SIB)

Reliability and validity of the Norwegian version of the Severe Impairment Battery (SIB)

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

Neurological complications of psychiatric drugs: clinical features and management

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