Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-26T03:38:48.492Z Has data issue: false hasContentIssue false
  • English
  • Français

Viewpoint: do antipsychotics protect against early death? A critical view

Published online by Cambridge University Press:  14 October 2020

Robert Whitaker Open the ORCID record for Robert Whitaker [Opens in a new window]
Robert Whitaker*
Affiliation:
Mad in America Foundation, 02139Cambridge, MA, USA
*
Author for correspondence: Robert Whitaker, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

In the past 15 years, researchers utilizing prescription databases to assess medication usage have concluded that antipsychotics reduce mortality in patients diagnosed with schizophrenia and other psychotic disorders. These findings stand in contrast to studies in non-psychiatric patients that have found that antipsychotics, because of their adverse effects on physical health, increase the risk of early death. A critical review of the evidence reveals that the worry remains. There is reason to conclude that antipsychotics contribute to the ‘mortality gap’ between the seriously mentally ill and the general population and that the database studies are plagued with methodological and reporting issues. Most importantly, the database studies tell of mortality rates within a drug-centered paradigm of care, which confounds any comparison of mortality risks when patients are on or off antipsychotics.

Keywords

Antipsychoticsmortalityschizophreniaseriously mentally ill
Type
Invited Review
Information
Psychological Medicine , Volume 50 , Issue 16 , December 2020 , pp. 2643 - 2652
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Albert, N., Randers, L., Allott, K., Jensen, H. D., Melau, M., Hjorthøj, C., & Nordentoft, M. (2019). Cognitive functioning following discontinuation of antipsychotic medication. A naturalistic sub-group analysis from the OPUS II trial. Psychological Medicine, 49(7), 1138–1147. doi:10.1017/S0033291718001836.CrossRefGoogle ScholarPubMed
Atbaşoglu, E. C., Schultz, S. K., & Andreasen, N. C. (2001). The relationship of akathisia with suicidality and depersonalization among patients with schizophrenia. Journal of Neuropsychiatry and Clinical Neurosciences, 13(3), 336–341. doi:10.1176/jnp.13.3.336.CrossRefGoogle Scholar
Basciotta, M., Zhou, W., Ngo, L., Donnino, M., Marcantanio, E. R., & Herzig, S. J. (2020). Antipsychotics and the risk of morality or cardiopulmonary arrest in hospitalized adults. Journal of the American Geriatrics Society, 68(3), 544–550. doi:10.1111/jgs.16246.CrossRefGoogle ScholarPubMed
Bergström, T., Seikkula, J., Alakare, B., Mäki, P., Köngäs-Saviaro, P., Taskila, J. J., … Aaltonen, J. (2018). The family-oriented open dialogue approach in the treatment of first-episode psychosis: Nineteen-year outcomes. Psychiatry Research, 270, 168–175. doi:10.1016/j.psychres.2018.09.039.CrossRefGoogle ScholarPubMed
Calsolaro, V., Antognoli, R., Okoye, C., & Monzani, F. (2019). The use of antipsychotic drugs for treating behavioral symptoms in Alzheimer's disease. Frontiers in Pharmacology Dec 6, 10, 1465. doi:10.3389/fphar.2019.01465.CrossRefGoogle ScholarPubMed
Carlborg, A., Winnerbäck, K., Jönsson, E. G., Jokinen, J., & Nordström, P. (2010). Suicide in schizophrenia. Expert Review of Neurotherapeutics, 10(7), 1153–1164. doi:10.1586/ern.10.82.CrossRefGoogle Scholar
Correll, C. U., Detraux, J., De Lepeleire, J., & De Hert, M. (2015). Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry, 14(2), 119–136. doi: 10.1002/wps.20204.CrossRefGoogle ScholarPubMed
Cullen, B. A., McGinty, E., Zhang, Y., dosReis, S. C., Steinwachs, D. M., Guallar, E., & Daumit, G. L. (2013). Guideline-concordant antipsychotic use and mortality in schizophrenia. Schizophenia Bulletin, 39(5), 1159–1168. doi:10.1093/schbul/sbs097.CrossRefGoogle Scholar
De Hert, M., Correll, C. U., & Cohen, D. (2010). Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of the FIN-11 study. Schizophrenia Research, 117(1), 68–74. doi:10.1016/j.schres.2009.12.029.CrossRefGoogle ScholarPubMed
Farberow, N., Ganzler, S., & Cuttler, F. (1978). Status of suicides in veterans administrations hospitals. Reports 2–4. Los Angeles, CA: Central Research Unit, V.A. Wadsworth Hospital Center.Google Scholar
Gardos, G., Cole, J. O., & Tarsy, D. (1978). Withdrawal syndromes associated with antipsychotic drugs. American Journal of Psychiatry, 135(11), 1321. doi:10.1176/ajp.135.11.1321.Google ScholarPubMed
Goff, D. C., Falkai, P., Fleischhacker, W. W., Girgis, R. R., Kahn, R. M., Uchida, H., … Lieberman, J. A. (2017). The long-term effects of antipsychotic medication on clinical course in schizophrenia. American Journal of Psychiatry, 174(9), 840–849. doi:10.1176/appi.ajp.2017.16091016.CrossRefGoogle Scholar
Harrison, S. L., Sluggett, J. K., Lang, C., Whitehead, C., Crotty, M., Corlis, M., … Inacio, M. C. (2020). Initiation of antipsychotics after moving to residential aged care facilities and mortality: A national cohort study. Aging Clinical and Experimental Research March 11. Online ahead of print. doi: 10.1007/s40520-020-01518-y.CrossRefGoogle ScholarPubMed
Harrow, M., & Jobe, T. H. (2007). Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: A 15-year multifollow-up study. Journal of Nervous and Mental Disease, 195(5), 406–414. doi:10.1097/01.nmd.0000253783.32338.6e.CrossRefGoogle Scholar
Hayes, J., Marston, L., Walters, K., King, M. B., & Osborn, D. P. J. (2017). Mortality gap for people with bipolar disorder and schizophrenia: UK-based cohort study 2000–2014. British Journal of Psychiatry, 211(3), 175–181. doi:10.1192/bjp.bp.117.202606.CrossRefGoogle ScholarPubMed
Healy, D., Harris, M., Tranter, R., Gutting, P., Austin, R., Jones-Edwards, G., & Roberts, A. P. (2006). Lifetime suicide rates in treated schizophrenia: 1875–1924 and 1994–1998 cohorts compared. British Journal of Psychiatry, 188, 223–228. doi:10.1192/bjp.188.3.223.CrossRefGoogle ScholarPubMed
Herings, R., & Erkens, J. (2003). Increased suicide attempt rate among patients interrupting use of atypical antipsychotics. Pharmacoepidemology and Drug Safety, 12(5), 423–424. doi:10.1002/pds.837.CrossRefGoogle ScholarPubMed
Hoang, U., Stewart, R., & Goldacre, M. (2011). Mortality after hospital discharge for people with schizophrenia or bipolar disorder: Retrospective study of linked English hospital episode statistics, 1999–2006. BMJ, 343, d5422. doi:10.1136/bmj.d5422.CrossRefGoogle ScholarPubMed
Hor, K., & Taylor, M. (2010). Suicide and schizophrenia: A systematic review of rates and risk factors. Journal of Psychopharmacology, 24(4 Suppl), 81–90. doi:10.1177/1359786810385490.CrossRefGoogle ScholarPubMed
Hussar, A. E. (1962). Effect of tranquilizers on medical morbidity and mortality in a mental hospital. JAMA, 179, 682–686. doi:10.1001/jama.1962.03050090010002.CrossRefGoogle Scholar
Jayatilleke, N., Hayes, R. D., Chang, C.-K., & Stewart, R. (2018). Acute general hospital admissions in people with serious mental illness. Psychological Medicine, 48(16), 2676–2683. doi:10.1017/S0033291718000284.CrossRefGoogle ScholarPubMed
Jennum, P., Baandrup, L., Ibsen, R., & Kjellberg, J. (2015). Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: A population-based register study. European College of Neuropsychopharmacology, 25(11), 1906–1913. doi:10.1016/j.euroneuro.2015.08.014.CrossRefGoogle ScholarPubMed
Johns Hopkins Medicine (2012) Use of antipsychotic drugs improves life expectancy for individuals with schizophrenia. Science Daily. 1, November 2012. https://www.sciencedaily.com/releases/2012/11/121101073152.htm.Google Scholar
Joukamaa, M., Heliövaara, M., Knekt, P., Aromaa, A., Raitasalo, R., & Lehtinen, V. (2006). Schizophrenia, neuroleptic medication and mortality. British Journal of Psychiatry Feb, 188, 122–127. doi:10.1192/bjp.188.2.122.CrossRefGoogle ScholarPubMed
Kasckow, J., Felmet, K., & Zisook, S. (2011). Managing suicide risk in patients with schizophrenia. CNS Drugs, 25(2), 129–143. doi:10.2165/11586450-000000000-00000CrossRefGoogle ScholarPubMed
Khan, A., Faucett, J., Morrison, S., & Brown, W. A. (2013). Comparative mortality risk in adult patients with schizophrenia, depression, bipolar disorder, anxiety disorders, and attention-deficit/hyperactivity disorder participating in psychopharmacology clinical trials. JAMA Psychiatry, 70(10), 1091–10999. doi:10.1001/jamapsychiatry.2013.149.CrossRefGoogle ScholarPubMed
Kiviniemi, M. (2014). Mortality, disability, psychiatric treatment and medication in first-onset schizophrenia in Finland: the register linkage study. Doctoral dissertation, University of Oulo, Finland. Accessed on May 28, 2020: http://jultika.oulu.fi/files/isbn9789526206325.pdf.Google Scholar
Larsen-Barr, M. (2016). Experiencing antipsychotic medication: from first prescriptions to attempted discontinuation. Ph.D. thesis, University of Auckland. Accessed on August 7, 2020: https://www.researchgate.net/publication/309485009_Experiencing_Antipsychotic_Medication_From_First_Prescriptions_to_Attempted_Discontinuation.Google Scholar
Larsen-Barr, M., Seymour, F., Read, J., & Gibson, K. (2018). Attempting to stop antipsychotic medication: Success, supports, and efforts to cope. Social Psychiatry and Psychiatric Epidemiology, 53(7), 745–756. doi:10.1007/s00127-018-1518-x.CrossRefGoogle Scholar
Lawrence, D., Kisely, S., & Pais, J. (2010). The epidemiology of excess mortality in people with mental illness. Canadian Journal of Psychiatry, 55(12), 752–760. doi:10.1177/070674371005501202.CrossRefGoogle ScholarPubMed
Maust, D. T., Kim, H. M., Seyfried, L. S., Chiang, C., Kavanagh, J., Schneider, L. S., & Kales, H. C. (2015). Antipsychotics, other psychotropics, and the risk of death in patients with dementia, number needed to harm. JAMA Psychiatry, 72(5), 438–445. doi:10.1001/jamapsychiatry.2014.3018.CrossRefGoogle Scholar
Moncrieff, J. (2006). Why is it so difficult to stop psychiatric drug treatment? It may be nothing to do with the original problem. Medical Hypotheses, 67(3), 517–523. doi:10.1016/j.mehy.2006.03.009.CrossRefGoogle Scholar
Moncrieff, J., Cohen, D., & Porter, S. (2013). The psychoactive effects of psychiatric medication: The elephant in the room. Journal of Psychoactive Drugs, 45(5), 409–415. doi:10.1080/02791072.2013.845328.CrossRefGoogle ScholarPubMed
Mortensen, P. B., & Juel, K. (1993). Mortality and causes of death in first admitted schizophrenic patients. British Journal of Psychiatry, 163, 183–189. doi:10.1192/bjp.163.2.183.CrossRefGoogle ScholarPubMed
Moser, D. J., Reese, R. L., Schultz, S. K., Benjamin, M. L., Arndt, S., Fleming, F. W., & Andreasen, N. C. (2005). Informed consent in medication-free schizophrenia research. American Journal of Psychiatry, 162(6), 1209–1211. doi:10.1176/appi.ajp.162.6.1209.CrossRefGoogle ScholarPubMed
Murray-Thomas, T., Jones, M. E., Patel, D., Brunner, E., Shatapathy, C. C., Motsko, S., … Van Staa, T. P. (2013). Risk of mortality (including sudden cardiac death) and major cardiovascular events in atypical and typical antipsychotic users: A study with the General Practice Research Database. Cardiovascular Psychiatry and Neurology, published online December 26, 2013:247486. doi: 10.1155/2013/247486.CrossRefGoogle ScholarPubMed
Murray, R. M. (2017). Mistakes I have made in my research career. Schizophrenia Bulletin, 43(2), 253–256. doi:10.1093/schbul/sbw165.Google Scholar
Olfson, M., Gerhard, T., Huang, C., Crystal, S., & Stroup, T. S. (2015). Premature mortality among adults with schizophrenia in the United States. JAMA Psychiatry, 72(12), 1172–1181. doi:10.1001/jamapsychiatry.2015.1737.CrossRefGoogle ScholarPubMed
Parks, J., Svendsen, D., Singer, P., & Foti, M. E. (2006). Morbidity and mortality in people with serious mental illness. Alexandria, VA: National Association of State Mental Health Program Directors. Retrieved from: https://www.nasmhpd.org/sites/default/files/Mortality%20and%20Morbidity%20Final%20Report%208.18.08_0.pdf.Google Scholar
Ralph, S. J., & Espinet, A. J. (2018). Increased all-cause mortality by antipsychotic drugs: Updated review and meta-analysis in dementia and general mental health care. Journal of Alzheimer's Disease Reports, 2(1), 1–26. doi:10.3233/ADR-170042.CrossRefGoogle ScholarPubMed
Ray, W. A., Chung, C. P., Murray, K. T., Hall, K., & Stein, C. M. (2009). Atypical antipsychotic drugs and the risk of sudden cardiac death. NEJM, 360(3), 225–235. doi:10.1056/NEJMoa0806994.CrossRefGoogle ScholarPubMed
Ray, W. A., Stein, C. M., Murray, K. T., Fuchs, D. C., Patrick, S. W., Daugherty, J., … Cooper, W. O. (2019). Association of antipsychotic treatment with risk of unexpected death among children and youths. JAMA Psychiatry, 76(2), 162–171. doi:10.1001/jamapsychiatry.2018.3421.CrossRefGoogle ScholarPubMed
Read, J., & Williams, J. (2019). Positive and negative effects of antipsychotic medication: An international online survey of 832 recipients. Current Drug Safety, 14(3), 173–181. doi:10.2174/1574886314666190301152734CrossRefGoogle ScholarPubMed
Saha, S., Chant, D., & McGrath, J. (2007). A systematic review of mortality in schizophrenia: Is the differential mortality gap worsening over time? Archives of General Psychiatry, 64(10), 1123–1131. doi:10.1001/archpsyc.64.10.1123.CrossRefGoogle ScholarPubMed
Salem, H., Nagpal, C., PIgott, T., & Texeira, A. L. (2017). Revisiting antipsychotic-induced akathisia: Current issues and prospective challenges. Current Neuropharmacology, 15(5), 789–798. doi:10.2174/1570159X14666161208153644.CrossRefGoogle ScholarPubMed
SANE Australia (2002). Schizophrenia: Costs. An analysis of the burden of schizophrenia and related suicide in Australia. Australia: Author. Retrieved from: https://www.madinamerica.com/wp-content/uploads/2020/04/Schizophrenia-suicideaustralia.pdf.Google Scholar
Schoenbaum, M., Sutherland, J. M., Chappel, A., Azrin, S., Goldstein, A. B., Rupp, A., & Heinssen, R. K. (2017). Twelve-month health care use and mortality in commercially insured young people with incident psychosis in the United States. Schizophrenia Bulletin, 43(6), 1262–1272. doi:10.1093/schbul/sbx009.CrossRefGoogle ScholarPubMed
Sher, L., & Kahn, R. (2019). Suicide in schizophrenia: An educational overview. Medicina (Kaunas), 55(7), 361. doi:10.3390/medicina55070361CrossRefGoogle Scholar
Taipale, H., Tanskanen, A., Mehtälä, J., Vattulainen, J., Correll, C. U., & Tiihonen, J. (2020). 20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62250 patients with schizophrenia (FIN20). World Psychiatry, 19(1), 61–68. doi:10.1002/wps.20699.CrossRefGoogle Scholar
Tiihonen, J., Lönnqvist, J., Wahlbeck, K., Klaukka, T., Niskanen, L., Tanskanen, A., & Haukka, J. (2009). 11-year follow-up of mortality in patients with schizophrenia: A population-based cohort study (FIN11 study). Lancet (London, England), 374(9690), 620–627. doi:10.1016/S0140-6736(09)60742-X.CrossRefGoogle Scholar
Tiihonen, J., Mittendorfer-Rutz, E., Torniainen, M., Alexanderson, K., & Tanskanen, A. (2016). Mortality and cumulative exposure to antipsychotics, antidepressants, and benzodiazepines in patients with schizophrenia: An observational follow-up study. American Journal of Psychiatry, 173(6), 600–606. doi:10.1176/appi.ajp.2015.15050618.CrossRefGoogle Scholar
Tiihonen, J., Tanskanen, P., & Taipale, H. (2018). 20-year Nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia. American Journal of Psychiatry, 175(8), 765–773. doi:10.1176/appi.ajp.2018.17091001.CrossRefGoogle ScholarPubMed
Tiihonen, J., Wahlbeck, K., Lönnqvist, J., Klaukka, T., Ioannidis, J. P. A., Volavka, J., & Haukka, J. (2006). Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: Observational follow-up study. BMJ, 333(7561), 224. doi:10.1136/bmj.38881.382755.2F.CrossRefGoogle Scholar
Torniainen, M., Mittendorfer-Rutz, E., Tanskanen, A., Björkenstam, C., Suvisaari, J., Alexanderson, K., & Tiihonen, J. (2015). Antipsychotic treatment and mortality in schizophrenia. Schizophrenia Bulletin, 41(3), 656–663. doi:10.1093/schbul/sbu164CrossRefGoogle Scholar
Tranter, R., & Healy, D. (1998). Neuroleptic discontinuation syndromes. Journal of Psychopharmacology, 12(4), 401–406. doi:10.1177/026988119801200412.CrossRefGoogle ScholarPubMed
Tumolo, J. (2018). Antipsychotics appear to halve mortality risk in schizophrenia. Psychiatry & Behavioral Health Learning Network, January 17, 2018. Published online: https://www.psychcongress.com/article/antipsychotics-appear-halve-mortality-risk-schizophre.https://www.psychcongress.com/article/antipsychotics-appear-halve-mortality-risk-schizophrenia.Google Scholar
Waddington, J. L., Youssef, H. A., & Kinsella, A. (1998). Mortality in schizophrenia. Antipsychotic polypharmacy and absence of adjunctive anticholinergics over the course of a 10-year prospective study. British Journal of Psychiatry, 173(10), 325–329. doi:10.1192/bjp.173.4.325.CrossRefGoogle ScholarPubMed
Weintraub, D., Chiang, C., Kim, H. M., Wilkinson, J., Marras, C., Stanislawski, B., … Kales, H. (2016). Association of antipsychotic use with mortality risk in patients with Parkinson disease. JAMA Neurology, 73(5), 535–541. doi:10.1001/jamaneurol.2016.0031.CrossRefGoogle ScholarPubMed
World Health Organization (2015). Excess mortality in persons with severe mental disorders. Geneva, Switzerland: Author. WHO reference number: WHO/MSD/MER/16.5. Retrieved from: https://www.who.int/mental_health/evidence/excess_mortality_report/en/.Google Scholar
Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., & Nienhuis, F. (2013). Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: Long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry, 70(9), 913–920. doi:10.1001/jamapsychiatry.2013.19CrossRefGoogle ScholarPubMed