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Comparative mortality risks of antipsychotic medications in community-dwelling older adults

  • T. Gerhard (a1), K. Huybrechts (a2), M. Olfson (a3), S. Schneeweiss (a2), W. V. Bobo (a4), P. M. Doraiswamy (a5), D. P. Devanand (a3), J. A. Lucas (a6), C. Huang (a6), E. S. Malka (a6), R. Levin (a2) and S. Crystal (a7)...
Abstract
Background

All antipsychotic medications carry warnings of increased mortality for older adults, but little is known about comparative mortality risks between individual agents.

 Aims

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

 Method

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.
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Copyright
COPYRIGHT: © Royal College of Psychiatrists, 2014 
Corresponding author
Professor Tobias Gerhard, Ernest Mario School of Pharmacy, Rutgers University, 112 Paterson Street, New Brunswick, NJ 08901, USA. Email: tgerhard@rci.rutgers.edu
Footnotes
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∗

Parts of this paper were presented on 17 August 2011 at the 27th International Conference of the International Society for Pharmacoepidemiology in Chicago, Illinois, USA.

†

See editorial, pp. 4–5, this issue.

This work was supported by Agency for Healthcare Research and Quality/Food and Drug Administration (AHRQ/FDA) award HS017918 and AHRQ award HS016097.

Declaration of interest

P.M.D. has received research grants and advisory/speaking fees from several pharmaceutical companies, including antipsychotic manufacturers, for other research. He owns stock in AdverseEvents Inc. which was not involved in this project. D.P.D. has received research support from Novartis AG and Eli Lilly and has served as a consultant to Bristol-Myers Squibb.

Footnotes
References
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  • Cited by 25
  • Cited by
    Crossref Citations
    Crossref logo
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Maxwell, Colleen J. Campitelli, Michael A. Hogan, David B. Diong, Christina Austin, Peter C. Amuah, Joseph E. Lapane, Kate Seitz, Dallas P. Gill, Sudeep S. Gruneir, Andrea Wodchis, Walter P. and Bronskill, Susan E. 2018. Relevance of frailty to mortality associated with the use of antipsychotics among community-residing older adults with impaired cognition. Pharmacoepidemiology and Drug Safety,

    Silwanowicz, Ryan M. Maust, Donovan T. Seyfried, Lisa S. Chiang, Claire Stano, Claire and Kales, Helen C. 2017. Management of older adults with dementia who present to emergency services with neuropsychiatric symptoms. International Journal of Geriatric Psychiatry, Vol. 32, Issue. 12, p. 1233.

    Arnold, Inken Straube, Kati Himmel, Wolfgang Heinemann, Stephanie Weiss, Vivien Heyden, Laura Hummers-Pradier, Eva and Nau, Roland 2017. High prevalence of prescription of psychotropic drugs for older patients in a general hospital. BMC Pharmacology and Toxicology, Vol. 18, Issue. 1,

    Dennis, Michael Shine, Laura John, Ann Marchant, Amanda McGregor, Joanna Lyons, Ronan A. and Brophy, Sinead 2017. Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study. Neurology and Therapy, Vol. 6, Issue. 1, p. 57.

    Koponen, Marjaana Taipale, Heidi Lavikainen, Piia Tanskanen, Antti Tiihonen, Jari Tolppanen, Anna-Maija Ahonen, Riitta Hartikainen, Sirpa and Christensen, Ane N∅rgaard 2017. Risk of Mortality Associated with Antipsychotic Monotherapy and Polypharmacy Among Community-Dwelling Persons with Alzheimer’s Disease. Journal of Alzheimer's Disease, Vol. 56, Issue. 1, p. 107.

    Lohse, Martin J. and Müller-Oerlinghausen, Bruno 2017. Arzneiverordnungs-Report 2017. p. 681.

    Aftab, Awais and Shah, Asim A. 2017. Behavioral Emergencies. Psychiatric Clinics of North America, Vol. 40, Issue. 3, p. 449.

    El-Saifi, N. Moyle, W. Jones, C. and Tuffaha, H. 2016. Quetiapine safety in older adults: a systematic literature review. Journal of Clinical Pharmacy and Therapeutics, Vol. 41, Issue. 1, p. 7.

    Luijendijk, Hendrika J. de Bruin, Niels C. Hulshof, Tessa A. and Koolman, Xander 2016. Terminal illness and the increased mortality risk of conventional antipsychotics in observational studies: a systematic review. Pharmacoepidemiology and Drug Safety, Vol. 25, Issue. 2, p. 113.

    Hui, Thng Shu Wong, Agnes and Wijesinghe, Ruki 2016. A review on mortality risks associated with antipsychotic use in behavioral and psychologic symptoms of dementia (BPSD). Mental Health Clinician, Vol. 6, Issue. 5, p. 215.

    Hall, Ryan C. W. and Soliman, Sherif 2016. Comprehensive Guide to Post-Traumatic Stress Disorders. p. 1445.
    Lohse, Martin J. and Müller-Oerlinghausen, Bruno 2016. Arzneiverordnungs-Report 2016. p. 663.

    Wang, Liang-Jen Lee, Sheng-Yu Yuan, Shin-Sheng Yang, Kang-Chung Yang, Chun-Ju Lee, Tung-Liang and Shyu, Yu-Chiau 2016. Risk of Mortality Among Patients Treated With Antipsychotic Medications. Journal of Clinical Psychopharmacology, Vol. 36, Issue. 1, p. 9.

    Howard, Robert Costafreda, Sergi G. Karcher, Keith Coppola, Danielle Berlin, Jesse A. and Hough, David 2016. Baseline characteristics and treatment-emergent risk factors associated with cerebrovascular event and death with risperidone in dementia patients. British Journal of Psychiatry, Vol. 209, Issue. 05, p. 378.

    Shah, Asim A. and Aftab, Awais 2016. Should Physicians Prescribe Antipsychotics in Dementia?. Psychiatric Annals, Vol. 46, Issue. 2, p. 97.

    Schmedt, Niklas Kollhorst, Bianca Enders, Dirk Jobski, Kathrin Krappweis, Jutta Garbe, Edeltraut and Schink, Tania 2016. Comparative risk of death in older adults treated with antipsychotics: A population-based cohort study. European Neuropsychopharmacology, Vol. 26, Issue. 9, p. 1390.

    Selbæk, Geir Aarsland, Dag Ballard, Clive Engedal, Knut Langballe, Ellen Melbye Benth, Jūratė Šaltytė and Bergh, Sverre 2016. Antipsychotic Drug Use Is Not Associated With Long-Term Mortality Risk in Norwegian Nursing Home Patients. Journal of the American Medical Directors Association, Vol. 17, Issue. 5, p. 464.e1.

    Kuronen, Marja Kautiainen, Hannu Karppi, Pertti Hartikainen, Sirpa and Koponen, Hannu 2016. Antipsychotic drug use and associations with neuropsychiatric symptoms in persons with impaired cognition: a cross-sectional study. Nordic Journal of Psychiatry, Vol. 70, Issue. 8, p. 621.

    Frölich, L. and Hausner, L. 2015. Therapie mit Antipsychotika und Antidepressiva bei Demenzen. Der Nervenarzt, Vol. 86, Issue. 4, p. 461.

    Peisah, Carmelle Strukovski, Julie-Anne Wijeratne, Chanaka Mulholland, Rosalind Luscombe, Georgina and Brodaty, Henry 2015. The development and testing of the quality use of medications in dementia (QUM-D): a tool for quality prescribing for behavioral and psychological symptoms of dementia (BPSD). International Psychogeriatrics, Vol. 27, Issue. 08, p. 1313.

    Download full list
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  • Access

Comparative mortality risks of antipsychotic medications in community-dwelling older adults

  • T. Gerhard (a1), K. Huybrechts (a2), M. Olfson (a3), S. Schneeweiss (a2), W. V. Bobo (a4), P. M. Doraiswamy (a5), D. P. Devanand (a3), J. A. Lucas (a6), C. Huang (a6), E. S. Malka (a6), R. Levin (a2) and S. Crystal (a7)...
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eLetters

Do antipsychotics have a role in reducing mortality risk?

Natalie M. Da Silva, CT1 Doctor
12 August 2014

We found Gerhard et al's article (1) highly relevant to our practise and the study cohort of 136,393 patients with new antipsychotic treatment episodes gives it considerable weight.

We would like to draw the reader's attention to Ray et al.'s paper (2) which compared cohort arms of more than 40,000 patients each. It does not focus on the mortality effect in the dementia or even older populationbut does suggest that typical and atypical antipsychotic drugs have a similar dose-related increased risk of sudden cardiac death in patients with psychosis and bipolar affective disorder. This is higher than non-users of antipsychotic drugs. Further in support of this is ZYPADHERA's summary of product characteristics (3) which documents the incidence of death to be higher in olanzapine versus the placebo group, independent of risk factors such as age > 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions or concomitant use of benzodiazepines.

However, Tiihonen's 11-year follow-up of mortality in patients with schizophrenia (4), concludes that long-term treatment with antipsychotic drugs is associated with lower mortality compared with no antipsychotic use.

We wonder what trends one would observe were we to look at the same for antipsychotic use for behavioural problems versus licensed indications. Clearly the risks will be higher in patients with behaviouraldisturbances and to do nothing is unacceptable.

In the article, we do appreciate that the dose-response findings are consistent with an increased absolute mortality risk associated with antipsychotic medications but that is not controlled for by other medication or pre-existing cardiac status. Moreover, exclusion of patientson antipsychotic and antidepressant combinations is stated yet haloperidolwas selectively used in patients not suffering from depression! The SPC for haloperidol has a requirement of pre-treatment ECG and we wonder if this had been carried out whether it would have eliminated one of the confounding factors.

Gerhard's paper again clearly identified that only a third of patients had dementia and, as raised by the authors, that there was no inclusion of an untreated comparison group. Hence this leaves the findingsdifficult to apply on a day- to-day basis.

We wonder whether the conclusions drawn by the authors are perhaps too wide due to factors such as uncertainty of diagnosis, co-prescription and severity of behavioural disturbance, which has not been controlled for. Perhaps to have a more meaningful outcome it would be interesting to further analyse data in the third of patients with dementia and look at the dose-response relationship when co-prescribing is controlled for. We would welcome that information particularly if it included a comparison group of patients suffering from dementia (with behavioural problems) who were not treated with antipsychotic medication.

REFERENCES1. Gerhard T, Huybrechts K, Olfson M, Schneeweiss S, Bobo WV, Doraiswamy PM,Devanand DP, Lucas JA, Huang C, Malka ES, Levin R, Crystal S. Comparative mortality risks of antipsychotic medications in community-dwelling older adults. Br J Psychiatry. 2014 Jul;205(1):44-51

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Conflict of interest: None declared

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