Antipsychotics and mortality: adjusting for mortality risk scores to address confounding by terminal illness.
OBJECTIVE
To determine whether adjustment for prognostic indices specifically developed for nursing home (NH) populations affect the magnitude of previously observed associations between mortality and conventional and atypical antipsychotics.


METHODS
Cohort study.


METHODS
A merged data set of Medicaid, Medicare, Minimum Data Set (MDS), Online Survey Certification and Reporting system, and National Death Index for 2001 to 2005.


METHODS
Dual-eligible individuals aged 65 and older who initiated antipsychotic treatment in a NH (N=75,445).


METHODS
Three mortality risk scores (Mortality Risk Index Score, Revised MDS Mortality Risk Index, Advanced Dementia Prognostic Tool) were derived for each participant using baseline MDS data, and their performance was assessed using c-statistics and goodness-of-fit tests. The effect of adjusting for these indices in addition to propensity scores (PSs) on the association between antipsychotic medication and mortality was evaluated using Cox models with and without adjustment for risk scores.


RESULTS
Each risk score showed moderate discrimination for 6-month mortality, with c-statistics ranging from 0.61 to 0.63. There was no evidence of lack of fit. Imbalances in risk scores between conventional and atypical antipsychotic users, suggesting potential confounding, were much lower within PS deciles than the imbalances in the full cohort. Accounting for each score in the Cox model did not change the relative risk estimates: 2.24 with PS-only adjustment versus 2.20, 2.20, and 2.22 after further adjustment for the three risk scores.


CONCLUSIONS
Although causality cannot be proven based on nonrandomized studies, this study adds to the body of evidence rejecting explanations other than causality for the greater mortality risk associated with conventional antipsychotics than with atypical antipsychotics.
Department of Epidemiology, School of Public Health, Harvard University, Boston, Massachusetts; Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, School of Medicine, Harvard University, Boston, Massachusetts.
Yoonyoung
Y
Park
Jessica M
JM
Franklin
Sebastian
S
Schneeweiss
Raisa
R
Levin
Stephen
S
Crystal
Tobias
T
Gerhard
Krista F
KF
Huybrechts
D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D003704:Dementia / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D009735:Nursing Homes; D011379:Prognosis; D020379:Risk Adjustment; D019452:Terminally Ill
D014150:Antipsychotic Agents
antipsychotics; confounding; mortality; nursing homes; pharmacoepidemiology