Comparative mortality risks of antipsychotic medications in community-dwelling older adults.
BACKGROUND
All antipsychotic medications carry warnings of increased mortality for older adults, but little is known about comparative mortality risks between individual agents.


OBJECTIVE
To estimate the comparative mortality risks of commonly prescribed antipsychotic agents in older people living in the community.


METHODS
A retrospective, claims-based cohort study was conducted of people over 65 years old living in the community who had been newly prescribed risperidone, olanzapine, quetiapine, haloperidol, aripiprazole or ziprasidone (n = 136 393). Propensity score-adjusted Cox proportional hazards models assessed the 180-day mortality risk of each antipsychotic compared with risperidone.


RESULTS
Risperidone, olanzapine and haloperidol showed a dose-response relation in mortality risk. After controlling for propensity score and dose, mortality risk was found to be increased for haloperidol (hazard ratio (HR) = 1.18, 95% CI 1.06-1.33) and decreased for quetiapine (HR = 0.81, 95% CI 0.73-0.89) and olanzapine (HR = 0.82, 95% CI 0.74-0.90).


CONCLUSIONS
Significant variation in mortality risk across commonly prescribed antipsychotics suggests that antipsychotic selection and dosing may affect survival of older people living in the community.
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
T
T
Gerhard
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
K
K
Huybrechts
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
M
M
Olfson
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
S
S
Schneeweiss
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
W V
WV
Bobo
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
P M
PM
Doraiswamy
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
D P
DP
Devanand
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
J A
JA
Lucas
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
C
C
Huang
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
E S
ES
Malka
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
R
R
Levin
Tobias Gerhard, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, and Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Krista Huybrechts, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Mark Olfson, MD MPH, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Sebastian Schneeweiss, MD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; William V. Bobo, MD, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee; P. Murali Doraiswamy, MD, Department of Psychiatry, Duke University Medical Center, Durham, North Carolina; D. P. Devanand, MD, Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and the New York State Psychiatric Institute, New York, New York; Judith A. Lucas, EdD RN, Cecilia Huang, PhD, Edmond S. Malka, PhD, MPH, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey; Raisa Levin, MS, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Stephen Crystal, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, New Jersey, USA.
S
S
Crystal
D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D009026:Mortality; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000401:mortality*; D012111:Residence Characteristics; D012189:Retrospective Studies; D012306:Risk
D014150:Antipsychotic Agents