FCM Evidence-based Medicine Journal Club : Antipsychotic Therapy and Short-term Serious Events in Older Adults with Dem

1. FCM Evidence-based Medicine Journal Club :�Antipsychotic Therapy and Short-term Serious Events in Older Adults with Dementia� Anika Russell, MD July 8, 2009

2. A Case Study: Ms. Bea Haveur is an 88 year old woman with a diagnosis of dementia who is brought to your office by her adult son and daughter-in law. They express concerns that lately she has become hostile, even violent at times. They are worried about her safety around their 2 young children. They wonder if there is some sort of medication that might help with this problem�.

3. The Paper:

4. Background and Significance: Aggression, agitation, delusions, and neuropsychiatric symptoms are common complications of dementia in elders. Along with environmental and behavioral interventions, antipsychotic drugs are frequently used to treat these behaviors. However, recently, a number of studies have raised important concerns about the safety of antipsychotic medications in the treatment of dementia in elderly patients.

5. Background and Significance, continued� Recent studies have suggested that elderly patients treated with antipsychotic medications may be at an increased risk of serious adverse events including: falls hip fractures CVA EPS, and death April 2005- FDA public health advisory warning: the use of atypical antipsychotic agents nearly doubled the risk of death in persons with dementia.

6. The Study Question: What is the short-term risk of any serious adverse event associated with the use of antipsychotic drugs in a population- based cohort of elderly adults with dementia? Antipsychotic meds often given in outpatient practice for treatment of agitation and in institutional settings, frequently around the time of admission. Given frequency of short term use of these agents, need to evaluate risk of short-term adverse outcomes.Antipsychotic meds often given in outpatient practice for treatment of agitation and in institutional settings, frequently around the time of admission. Given frequency of short term use of these agents, need to evaluate risk of short-term adverse outcomes.

7. Study Design and Data Sources: Population-based, retrospective cohort study Used linked administrative health care data from Ontario, Canada between April 1st, 1997 and March 31st, 2004

8. Study Population: Adults, ages 66 and older, residing in Ontario, Canada, with a diagnosis of dementia and a new rx for an antipsychotic medication during a 7 year period, plus a matched group of adults with dementia receiving at least 1 new rx for a non-antipsychotic medication during the same period.

9. Exclusion Criteria: Schizophrenia tics Huntington�s dz Dialysis hx of parkinsonism EPS during past 5 yrs hx of brain tumor Epilepsy Trauma pathological fractures or hip fractures individuals receiving palliative care

10. Subgroups for Analysis: 2 major subgroups: Community dwelling group: residing in community Nursing home group: if index rx submitted from a nursing home

11. Subgroups for Analysis, continued: Within subgroups, separated patients receiving antipsychotics into: Atypical (e.g. olanzapine, quetiapine, risperidone), and Conventional (e.g. haloperidol, loxapine, and thioridazine) Patients receiving antipsychotics were compared to a group of adults with dementia receiving at least 1 new rx for a non-antipsychotic medication during the same period (�None� or control group) Propensity matched

12. Subgroups for analysis:

13. Outcomes: Primary outcome: any serious event within 30 days Defined as hospitalization or death within 30 days of cohort entry For conventional antipsychotic vs. non-antipsychotic and for atypical antipsychotic vs. non-antipsychotic Community dwelling and institutionalized adults analyzed separately Secondary outcomes: Death, hospitalization due to any of several conditions previously associated with the use of antipsychotics (i.e. EPS, hip fractures, falls, and CVAs), and hospitalization for other reasons Comparison of excess event rates between conventional and atypical antipsychotics

14. The Analysis: Conditional logistic regression model adjusted by propensity-based matching �No exposure� group used as reference Also performed covariate analysis to identify predictors of serious events: Community model: types of agents used, # of physician visits, # of hospital admissions, etc. Nursing home model: # of drugs used in previous year, # of visits to a psychiatrist, etc.

15. The Results: Community dwelling group: 3 propensity matched groups of 6894 individuals Nursing home group: 3 propensity matched groups of 6853 individuals. Most frequently prescribed atypical antipsychotic: risperidone> olanzapine> quetiapine Most frequently prescribed conventional antipsychotic: haloperidol >loxapine >thioridazine

16. The Results, cont�d:Risk of Any Serious Eventwithin 30 days of Starting Therapy