HHS Public Access Author manuscript Author Manuscript
J Am Geriatr Soc. Author manuscript; available in PMC 2017 November 01. Published in final edited form as: J Am Geriatr Soc. 2016 November ; 64(11): 2400. doi:10.1111/jgs.14506.
Reply to Antipsychotics: Mortality risk factor itself? Shoshana J. Herzig, MDa,b and Edward R. Marcantonio, MD, SMa,b,c aDivision
of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston,
MA
Author Manuscript
bHarvard
Medical School, Boston, MA
cDivision
of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA We are aware of several large observational studies that have demonstrated increased risk of mortality for new users of both typical and atypical antipsychotic medications.1–5 Additionally, Schneider et al performed a meta-analysis of data from 15 randomized controlled trials that demonstrated a hazard ratio for mortality of 1.54 (95% confidence intervals 1.06–2.23) for atypical antipsychotics compared to placebo.6 Nonetheless, we agree with Mayoral et al.7 that the association between antipsychotics and mortality in this large hospitalized patient population would be interesting as an additional investigation,
Author Manuscript
Corresponding author: Shoshana J. Herzig, MD, Address: Beth Israel Deaconess Medical Center, 1309 Beacon Street, Brookline, MA 02446 | Phone: (617) 510-1020 | [email protected]. Alternate corresponding author: Edward R. Marcantonio, MD, Address: Beth Israel Deaconess Medical Center, 1309 Beacon Street, #216, Brookline, MA 02446 | Phone: (617) 754-1405 | [email protected]. Conflict of Interest Checklist: Elements of Financial/Personal Conflicts
Herzig Yes
No
Marcantonio Yes
No
Author Manuscript
Employment or Affiliation
X
X
Grants/Funds
X
X
Honoraria
X
X
Speaker Forum
X
X
Consultant
X
X
Stocks
X
X
Royalties
X
X
Expert Testimony
X
X
Board Member
X
X
Patents
X
X
Personal Relationship
X
X
Herzig and Marcantonio
Page 2
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particularly given that the increased risk demonstrated in these prior community-based analyses has been greatest in the first 30 days of use,2, 5 and in short-term users.3 We found that in our cohort of 17,775 non-psychiatric hospitalizations,8 the unadjusted mortality rate was 2.1% among those unexposed to antipsychotic medications, and 7.5% among those exposed to antipsychotic medications. However, as noted by Mayoral et al., the increased mortality seen in the exposed group is likely to be at least partially explained by things like severity of illness, comorbidities, in-hospital complications, and inpatient palliative care, among others. To rigorously examine this association would require extensive statistical modeling and sensitivity analyses beyond the scope of what can be provided in this reply. We thank Drs. Mayoral et.al. for this excellent suggestion, and plan to further address this question in subsequent analyses.
Author Manuscript
Acknowledgments Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Marcantonio was funded by grant number K24AG035075 from the National Institute on Aging. The funding organizations had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
References
Author Manuscript
1. Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009; 360:225–235. [PubMed: 19144938] 2. Rossom RC, Rector TS, Lederle FA, Dysken MW. Are all commonly prescribed antipsychotics associated with greater mortality in elderly male veterans with dementia? J Am Geriatr Soc. 2010; 58:1027–1034. [PubMed: 20487081] 3. Straus SM, Bleumink GS, Dieleman JP, et al. Antipsychotics and the risk of sudden cardiac death. Arch Intern Med. 2004; 164:1293–1297. [PubMed: 15226162] 4. Trifiro G, Verhamme KM, Ziere G, Caputi AP, Ch Stricker BH, Sturkenboom MC. All-cause mortality associated with atypical and typical antipsychotics in demented outpatients. Pharmacoepidemiol Drug Saf. 2007; 16:538–544. [PubMed: 17036366] 5. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med. 2005; 353:2335–2341. [PubMed: 16319382] 6. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005; 294:1934–1943. [PubMed: 16234500] 7. Mayoral V, Villas Boas P, Jacinto A. Antipsychotics: Mortality risk factor itself? J Am Geriatr Soc. 2016 8. Herzig SJ, Rothberg MB, Guess JR, et al. Antipsychotic Use in Hospitalized Adults: Rates, Indications, and Predictors. J Am Geriatr Soc. 2016; 64:299–305. [PubMed: 26889839]
Author Manuscript J Am Geriatr Soc. Author manuscript; available in PMC 2017 November 01.
J Am Geriatr Soc. Author manuscript; available in PMC 2017 November 01. Published in final edited form as: J Am Geriatr Soc. 2016 November ; 64(11): 2400. doi:10.1111/jgs.14506.
Reply to Antipsychotics: Mortality risk factor itself? Shoshana J. Herzig, MDa,b and Edward R. Marcantonio, MD, SMa,b,c aDivision
of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston,
MA
Author Manuscript
bHarvard
Medical School, Boston, MA
cDivision
of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA We are aware of several large observational studies that have demonstrated increased risk of mortality for new users of both typical and atypical antipsychotic medications.1–5 Additionally, Schneider et al performed a meta-analysis of data from 15 randomized controlled trials that demonstrated a hazard ratio for mortality of 1.54 (95% confidence intervals 1.06–2.23) for atypical antipsychotics compared to placebo.6 Nonetheless, we agree with Mayoral et al.7 that the association between antipsychotics and mortality in this large hospitalized patient population would be interesting as an additional investigation,
Author Manuscript
Corresponding author: Shoshana J. Herzig, MD, Address: Beth Israel Deaconess Medical Center, 1309 Beacon Street, Brookline, MA 02446 | Phone: (617) 510-1020 | [email protected]. Alternate corresponding author: Edward R. Marcantonio, MD, Address: Beth Israel Deaconess Medical Center, 1309 Beacon Street, #216, Brookline, MA 02446 | Phone: (617) 754-1405 | [email protected]. Conflict of Interest Checklist: Elements of Financial/Personal Conflicts
Herzig Yes
No
Marcantonio Yes
No
Author Manuscript
Employment or Affiliation
X
X
Grants/Funds
X
X
Honoraria
X
X
Speaker Forum
X
X
Consultant
X
X
Stocks
X
X
Royalties
X
X
Expert Testimony
X
X
Board Member
X
X
Patents
X
X
Personal Relationship
X
X
Herzig and Marcantonio
Page 2
Author Manuscript
particularly given that the increased risk demonstrated in these prior community-based analyses has been greatest in the first 30 days of use,2, 5 and in short-term users.3 We found that in our cohort of 17,775 non-psychiatric hospitalizations,8 the unadjusted mortality rate was 2.1% among those unexposed to antipsychotic medications, and 7.5% among those exposed to antipsychotic medications. However, as noted by Mayoral et al., the increased mortality seen in the exposed group is likely to be at least partially explained by things like severity of illness, comorbidities, in-hospital complications, and inpatient palliative care, among others. To rigorously examine this association would require extensive statistical modeling and sensitivity analyses beyond the scope of what can be provided in this reply. We thank Drs. Mayoral et.al. for this excellent suggestion, and plan to further address this question in subsequent analyses.
Author Manuscript
Acknowledgments Dr. Herzig was funded by grant number K23AG042459 from the National Institute on Aging. Dr. Marcantonio was funded by grant number K24AG035075 from the National Institute on Aging. The funding organizations had no involvement in any aspect of the study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
References
Author Manuscript
1. Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009; 360:225–235. [PubMed: 19144938] 2. Rossom RC, Rector TS, Lederle FA, Dysken MW. Are all commonly prescribed antipsychotics associated with greater mortality in elderly male veterans with dementia? J Am Geriatr Soc. 2010; 58:1027–1034. [PubMed: 20487081] 3. Straus SM, Bleumink GS, Dieleman JP, et al. Antipsychotics and the risk of sudden cardiac death. Arch Intern Med. 2004; 164:1293–1297. [PubMed: 15226162] 4. Trifiro G, Verhamme KM, Ziere G, Caputi AP, Ch Stricker BH, Sturkenboom MC. All-cause mortality associated with atypical and typical antipsychotics in demented outpatients. Pharmacoepidemiol Drug Saf. 2007; 16:538–544. [PubMed: 17036366] 5. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med. 2005; 353:2335–2341. [PubMed: 16319382] 6. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005; 294:1934–1943. [PubMed: 16234500] 7. Mayoral V, Villas Boas P, Jacinto A. Antipsychotics: Mortality risk factor itself? J Am Geriatr Soc. 2016 8. Herzig SJ, Rothberg MB, Guess JR, et al. Antipsychotic Use in Hospitalized Adults: Rates, Indications, and Predictors. J Am Geriatr Soc. 2016; 64:299–305. [PubMed: 26889839]
Author Manuscript J Am Geriatr Soc. Author manuscript; available in PMC 2017 November 01.
