Antipsychotic medication and long-term mortality risk in patients with schizophrenia; a systematic review and meta-analysis.
Open accessAbstract
Patients with schizophrenia have a higher mortality risk than patients suffering from any other psychiatric disorder. Previous research is inconclusive regarding the association of antipsychotic treatment with long-term mortality risk. To this aim, we systematically reviewed the literature and performed a meta-analysis on the relationship between long-term mortality and exposure to antipsychotic medication in patients with schizophrenia. The objectives were to (i) determine long-term mortality rates in patients with schizophrenia using any antipsychotic medication; (ii) compare these with mortality rates of patients using no antipsychotics; (iii) explore the relationship between cumulative exposure and mortality; and (iv) assess causes of death. We systematically searched the EMBASE, MEDLINE and PsycINFO databases for studies that reported on mortality and antipsychotic medication and that included adults with schizophrenia using a follow-up design of more than 1 year. A total of 20 studies fulfilled our inclusion criteria. These studies reported 23,353 deaths during 821,347 patient years in 133,929 unique patients. Mortality rates varied widely per study. Meta-analysis on a subgroup of four studies showed a consistent trend of an increased long-term mortality risk in schizophrenia patients who did not use antipsychotic medication during follow-up. We found a pooled risk ratio of 0.57 (LL:0.46 UL:0.76 p value <0.001) favouring any exposure to antipsychotics. Statiscal heterogeneity was found to be high (Q = 39.31, I2 = 92.37%, p value < 0.001). Reasons for the increased risk of death for patients with schizophrenia without antipsychotic medication require further research. Prospective validation studies, uniform measures of antipsychotic exposure and classified causes of death are commendable.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823 · see citing works
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & The PRISMA Group (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000097 · Cited by 64,042 · see citing works
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.
(2009) · PubMed Central · Cited by 44,859 · see citing works
The Cochrane Collaboration's tool for assessing risk of bias in randomised trials
Higgins, J. P. T., Altman, D. G., Gotzsche, P. C., Juni, P., Moher, D., Oxman, A. D., Savovic, J., Schulz, K. F., Weeks, L., Sterne, J. A. C., et al. (2011) · BMJ · doi:10.1136/bmj.d5928 · Cited by 33,817 · see citing works
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2009) · doi:10.1002/9780470743386 · Cited by 14,225 · see citing works
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2021) · doi:10.1002/9781119558378 · Cited by 9,799 · see citing works
Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia
Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Keefe, R. S. E., Davis, S. M., Davis, C. E., Lebowitz, B. D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051688 · Cited by 5,892 · see citing works
Walker, E. R., McGee, R. E., & Druss, B. G. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.2502 · Cited by 2,976 · see citing works
Saha, S., Chant, D., & McGrath, J. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.10.1123 · Cited by 2,065 · see citing works
Meltzer, H. Y. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.1.82 · Cited by 1,393 · see citing works
Tiihonen, J., Lönnqvist, J., Wahlbeck, K., Klaukka, T., Niskanen, L., Tanskanen, A., & Haukka, J. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60742-x · Cited by 1,354 · see citing works
Lévesque, L. E., Hanley, J. A., Kezouh, A., & Suissa, S. (2010) · BMJ · doi:10.1136/bmj.b5087 · Cited by 1,199 · see citing works
Metabolic and cardiovascular adverse effects associated with antipsychotic drugs.
De Hert, M., Detraux, J., van Winkel, R., Yu, W., & Correll, C. U. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.156 · Cited by 1,145 · see citing works
Premature Mortality Among Adults With Schizophrenia in the United States
Olfson, M., Gerhard, T., Huang, C., Crystal, S., & Stroup, T. S. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.1737 · Cited by 1,083 · see citing works
Correll, C. U., Detraux, J., De Lepeleire, J., & De Hert, M. (2015) · World Psychiatry · doi:10.1002/wps.20204 · Cited by 820 · see citing works
Physical illness and schizophrenia: a review of the literature
Leucht, S., Burkard, T., Henderson, J., Maj, M., & Sartorius, N. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2007.01095.x · Cited by 633 · see citing works
Osborn, D. P. J., Levy, G., Nazareth, I., Petersen, I., Islam, A., & King, M. B. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.2.242 · Cited by 608 · see citing works
Randomized Trials or Observational Tribulations?
Pocock, S. J., & Elbourne, D. R. (2000) · New England Journal of Medicine · doi:10.1056/nejm200006223422511 · Cited by 550 · see citing works
Tiihonen, J., Wahlbeck, K., Lönnqvist, J. K., Klaukka, T., Ioannidis, J. P. A., Volavka, J., & Haukka, J. K. (2006) · BMJ · doi:10.1136/bmj.38881.382755.2f · Cited by 385 · see citing works
Schizophrenia, “Just the Facts” 5. Treatment and prevention Past, present, and future
Tandon, R., Nasrallah, H. A., & Keshavan, M. S. (2010) · Schizophrenia Research · doi:10.1016/j.schres.2010.05.025 · Cited by 385 · see citing works
Influence of antipsychotics on mortality in schizophrenia: systematic review
Weinmann, S., Read, J., & Aderhold, V. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.05.018 · Cited by 224 · see citing works
Antipsychotic treatment and mortality in schizophrenia.
Torniainen, M., Mittendorfer-Rutz, E., Tanskanen, A., Bjorkenstam, C., Suvisaari, J., Alexanderson, K., & Tiihonen, J. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu164 · Cited by 208 · see citing works
Developing improved observational methods for evaluating therapeutic effectiveness
Horwitz, R. I., Viscoli, C. M., Clemens, J. D., & Sadock, R. T. (1990) · The American Journal of Medicine · doi:10.1016/0002-9343(90)90182-d · Cited by 204 · see citing works
Review: Mortality in schizophrenia: a measurable clinical endpoint
Bushe, C. J., Taylor, M., & Haukka, J. (2010) · Journal of Psychopharmacology · doi:10.1177/1359786810382468 · Cited by 185 · see citing works
Alphs, L. D., Benson, C. J., Cheshire-Kinney, K., Lindenmayer, J., Mao, L., Rodriguez, S. C., & Starr, H. L. (2015) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.14m09584 · Cited by 137 · see citing works
Hayes, R. D., Downs, J. M., Chang, C., Jackson, R., Shetty, H., Broadbent, M., Hotopf, M. H., & Stewart, R. J. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu120 · Cited by 129 · see citing works
Gäebel, W., Schreiner, A., Bergmans, P., de Arce, R., Rouillon, F., Cordes, J., Eriksson, L., & Smeraldi, E. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.111 · Cited by 111 · see citing works
Khan, A., Faucett, J., Morrison, S., & Brown, W. A. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.149 · Cited by 109 · see citing works
Binder, M. D., Correll, C. U., & Cohen, D. (2010) · Schizophrenia Research · doi:10.1016/j.schres.2009.12.029 · Cited by 104 · see citing works
Taylor, D. M., Douglas-Hall, P., Olofinjana, B., Whiskey, E., & Thomas, A. (2009) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.108.051979 · Cited by 99 · see citing works
Impact of Clozapine on Completed Suicide
Sernyak, M. J., Desai, R. A., Stolar, M. J., & Rosenheck, R. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.6.931 · Cited by 97 · see citing works
Cardiovascular Disease Mortality in Patients With Chronic Schizophrenia Treated With Clozapine
Kelly, D. L., McMahon, R. P., Liu, F., Love, R. C., Wehring, H. J., Shim, J.-C., Warren, K. R., & Conley, R. R. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.08m04718yel · Cited by 90 · see citing works
Ran, M., Weng, X., Chan, C., Chen, E. Y. H., Tang, C., Lin, F.-R., Mao, W.-J., Hu, S., Huang, Y., & Xiang, M. (2015) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.114.157685 · Cited by 86 · see citing works
Haukka, J. K., Tiihonen, J., Härkänen, T., & Lönnqvist, J. K. (2008) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1579 · Cited by 84 · see citing works
Copeland, L. A., Zeber, J. E., Wang, C. P., Parchman, M. L., Lawrence, V. A., Valenstein, M. M., & Miller, A. L. (2009) · BMC Health Services Research · doi:10.1186/1472-6963-9-127 · Cited by 83 · see citing works
Guideline-Concordant Antipsychotic Use and Mortality in Schizophrenia
Cullen, B., McGinty, E. E., Zhang, Y., dosReis, S., Steinwachs, D. M., Güallar, E., & Daumit, G. L. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs097 · Cited by 73 · see citing works
Girgis, R. R., Phillips, M. R., Li, X., Li, K., Jiang, H., Wu, C., Duan, N., Niu, Y., & Lieberman, J. A. (2011) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.110.081471 · Cited by 71 · see citing works
Montout, C., Casadebaig, F., Lagnaoui, R., Verdoux, H., Philippe, A., Bégaud, B., & Moore, N. D. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(01)00325-5 · Cited by 69 · see citing works
Thomas, S. H. L., Drici, M. D., Hall, G. C., Crocq, M. A., Everitt, B., Lader, M. H., Jeunne, C. L., Naber, D., Priori, S., Sturkenboom, M., et al. (2010) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2010.01563.x · Cited by 67 · see citing works
Kasper, S. F., Möller, H., & Hale, A. S. (2009) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-009-0018-0 · Cited by 34 · see citing works
All-Cause Mortality and Medication Risk Factors in Schizophrenia
Tenback, D. E., Pijl, B. J., Smeets, H. M., van Os, J., & van Harten, P. N. (2011) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31823f3c43 · Cited by 34 · see citing works
Cordón, R. D. A., Eding, E., Teixeira, J. M., Milanova, V., Rancāns, E., & Schreiner, A. (2011) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-011-0220-8 · Cited by 21 · see citing works
Ritchie, C., Harrigan, S., Mastwyk, M., et al. (2009) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2354 · Cited by 20 · see citing works
Khan, A., Schwartz, K. A., Stern, C., Redding, N., Kolts, R. L., Brown, W. A., & Robinson, D. S. (2007) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v68n1201 · Cited by 17 · see citing works
Chen, V. C., Liao, Y., Lai, T.-J., Lane, H., Shao, W., Dewey, M. E., Lee, C. T., & Lu, M. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.10.005 · Cited by 12 · see citing works
Five-year patient outcomes with risperidone long-acting injection or oral aripiprazole
Deslandes, P. N., Dwivedi, M., & Sewell, R. D. E. (2015) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125315581997 · Cited by 5 · see citing works
Amisulpride for Older Patients With Long-Standing Schizophrenia
Pridan, S., Baruch, Y., Swartz, M., et al. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000226 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?
Correll, C. U., Rubio, J. M., & Kane, J. M. (2018) · World Psychiatry · doi:10.1002/wps.20516 · Cited by 324 · see citing works
The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses
Haddad, P. M., & Correll, C. U. (2018) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125318781475 · Cited by 259 · see citing works
Vermeulen, J. M., van Rooijen, G., van de Kerkhof, M. P. J., Sutterland, A. L., Correll, C. U., & de Haan, L. (2019) · Schizophrenia Bulletin · doi:10.1093/schbul/sby052 · Cited by 246 · see citing works
Self-citationKane, J. M., Schooler, N. R., Marcy, P., Correll, C. U., Achtyes, E. D., Gibbons, R. D., & Robinson, D. G. (2020) · JAMA psychiatry · doi:10.1001/jamapsychiatry.2020.2076 · Cited by 210 · see citing works
Carolan, A., Hynes-Ryan, C., Agarwal, S. M., Bourke, R., Cullen, W., Gaughran, F., Hahn, M. K., Krivoy, A., Lally, J., Leucht, S., et al. (2025) · Schizophrenia Bulletin · doi:10.1093/schbul/sbae205 · Cited by 70 · see citing works
Lee, K., Abraham, S., & Cleaver, R. (2022) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2022.07.006 · Cited by 53 · see citing works
Bogers, J. P. A. M., Hambarian, G., Michiels, M., Vermeulen, J., & de Haan, L. (2020) · Schizophrenia Bulletin Open · doi:10.1093/schizbullopen/sgaa002 · Cited by 33 · see citing works
Self-citation
- Authors
- Vermeulen, J., van Rooijen, G., Doedens, P., Numminen, E., van Tricht, M., & de Haan, L.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Vermeulen, J.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2017-04-11
- Volume
- 47
- Issue
- 13
- Pages
- 2217-2228
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2605936348
- Cited by
- 134
- References
- 48
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 20 · 2023: 28 · 2022: 20 · 2021: 11 · 2020: 14 · 2019: 9 · 2018: 12 · 2017: 2
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Keywords
- schizophrenia, antipsychotic drugs, long-term mortality, causes of death, untreated schizophrenia, mortality risk
- MeSH terms
- Humans, Schizophrenia, Antipsychotic Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
