Antipsychotic Dose in Acute Schizophrenia: A Meta-analysis
Open accessAbstract
Little is known regarding optimal antipsychotic doses in the acute phase of schizophrenia. The aim of the present study was to employ the concept of minimum effective dose (MED) in examining efficacy and tolerability within this population. MED was identified for each antipsychotic through a previous systematic review. We then identified double-blind placebo-controlled randomized trials that involved fixed-dose antipsychotic monotherapy in acute schizophrenia and compared the identified MED vs higher doses of the same oral antipsychotic. Studies were selected from a recent meta-analysis examining dose–response relationship of second-generation antipsychotics and haloperidol. We extracted the data on study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events. For each antipsychotic, we conducted a meta-analysis to compare outcomes between MED and 2-fold MED, and MED and 3-fold MED. A total of 26 studies involving 5618 patients were included in the meta-analysis. In terms of study discontinuation, significant differences were found in study discontinuation due to lack of efficacy between MED and higher doses, in favor of 2-fold and 3-fold MEDs. Regarding psychopathology, both 2-fold and 3-fold MEDs were superior to MED for total and positive symptom scores. As for side effects, 2-fold MED proved inferior to MED for parkinsonism scores and diarrhea, whereas 3-fold MED was inferior for akathisia, somnolence, and vomiting. Findings suggest that clinicians can dose an antipsychotic at 2-fold or 3-fold MED for patients with acute schizophrenia but should closely monitor side effects.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
LAIs have more restrictive dose limitations than oral treatments; however, high-dose LAI treatment has not been shown to be superior to LAI treatment at doses within the identified therapeutic range.
“Also, LAIs have more restrictive dose limitations than oral treatments; however, high-dose LAI treatment has not been shown to be superior to LAI treatment at doses within the identified therapeutic range [106–108].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [106]
The Abstract and Minimum Effective Doses of Antipsychotics section specify that this meta-analysis compares higher doses with minimum effective doses of oral antipsychotics. Searches for LAIs, injectable formulations, and their dose limits found no passage addressing either claim about LAI treatment. (LLM, conf=0.78)
Experimental — accuracy not yet measured
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
The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987) · Schizophrenia Bulletin · doi:10.1093/schbul/13.2.261 · Cited by 21,378 · see citing works
The Brief Psychiatric Rating Scale.
Overall, J. E., & Gorham, D. R. (1962) · Psychological Reports · doi:10.2466/pr0.1962.10.3.799 · Cited by 11,090 · see citing works
(1976) · Medical Entomology and Zoology · Cited by 8,899 · see citing works
A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS
Simpson, G. M., B., M., B., G., Angus, J. W. S., P., F. R. C., & M., D. P. (1970) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1970.tb02066.x · Cited by 3,265 · see citing works
A Rating Scale for Drug-Induced Akathisia
Barnes, T. R. E. (1989) · The British Journal of Psychiatry · doi:10.1192/bjp.154.5.672 · Cited by 2,179 · see citing works
Negative v Positive Schizophrenia
Andreasen, N. C. (1982) · Archives of General Psychiatry · doi:10.1001/archpsyc.1982.04290070025006 · Cited by 2,008 · see citing works
Huhn, M., Nikolakopoulou, A., Schneider-Thoma, J., Krause, M., Samara, M., Peter, N., Arndt, T., Bäckers, L., Rothe, P., Cipriani, A., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31135-3 · Cited by 1,753 · see citing works
Self-citationInternational Consensus Study of Antipsychotic Dosing
Gardner, D. M., Murphy, A. L., O'Donnell, H., Centorrino, F., & Baldessarini, R. J. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09060802 · Cited by 1,302 · see citing works
Risperidone in the treatment of schizophrenia
Marder, S. R., & Meibach, R. C. (1994) · American Journal of Psychiatry · doi:10.1176/ajp.151.6.825 · Cited by 1,194 · see citing works
Atypical antipsychotic drugs and the risk of sudden cardiac death
Ray, W. A., Chung, C. P., Murray, K. T., Hall, K., & Stein, C. M. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0806994 · Cited by 1,194 · see citing works
Chouinard, G., Jones, B., Remington, G. J., BLOOM, D., Addington, D. E., MacEwan, G. W., Labelle, A., Beauclair, L., & Arnott, W. S. (1993) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199302000-00004 · Cited by 876 · see citing works
Self-citationArvanitis, L. A., & Miller, B. G. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00190-x · Cited by 806 · see citing works
Peuskens, J. (1995) · The British Journal of Psychiatry · doi:10.1192/bjp.166.6.712 · Cited by 551 · see citing works
Daniel, D. G. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00090-6 · Cited by 376 · see citing works
Dose Equivalents for Second-Generation Antipsychotics: The Minimum Effective Dose Method
Leucht, S., Samara, M. T., Heres, S., Patel, M. X., Woods, S. W., & Davis, J. M. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu001 · Cited by 373 · see citing works
Self-citationKane, J. M., Skuban, A., Ouyang, J., Hobart, M., Pfister, S., McQuade, R. D., Nyilas, M., Carson, W. H., Sanchez, R., & Eriksson, H. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.01.038 · Cited by 325 · see citing works
ZIMBROFF, D. L., Kane, J. M., Tamminga, C. A., Daniel, D. G., Mack, R. J., Wozniak, P. J., Sebree, T. B., Wallin, B., & Kashkin, K. B. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.6.782 · Cited by 306 · see citing works
Dose-response meta-analysis of antipsychotic drugs for acute schizophrenia
Leucht, S., Crippa, A., Siafis, S., Patel, M. X., Orsini, N., & Davis, J. M. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19010034 · Cited by 301 · see citing works
Self-citationKane, J. M., Cañas, F., Kramer, M. L., Ford, L., Gassmann-Mayer, C., Lim, P., & Eerdekens, M. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.09.012 · Cited by 296 · see citing works
Keck, P. E., Buffenstein, A., Ferguson, J. M., Feighner, J. P., Jaffe, W., Harrigan, E. P., & Morrissey, M. R. (1998) · Psychopharmacology · doi:10.1007/s002130050755 · Cited by 265 · see citing works
Processing Speed Deficits in Schizophrenia: Reexamining the Evidence
Knowles, E. E. M., David, A. S., & Reichenberg, A. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09070937 · Cited by 261 · see citing works
Meltzer, H. Y., Cucchiaro, J. B., Silva, R., Ogasa, M., Phillips, D., Xu, J., Kalali, A. H., Schweizer, E. E., Pikalov, A., & Loebel, A. D. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10060907 · Cited by 249 · see citing works
Davidson, M., Emsley, R. A., Kramer, M. L., Ford, L., Pan, G., Lim, P., & Eerdekens, M. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.03.003 · Cited by 249 · see citing works
Marder, S. R., Kramer, M. L., Ford, L., Eerdekens, E., Lim, P., Eerdekens, M., & Lowy, A. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.01.017 · Cited by 229 · see citing works
Samara, M. T., Leucht, C., Leeflang, M., Anghelescu, I., Chung, Y., Crespo‐Facorro, B., Elkis, H., Hatta, K., Giegling, I., Kane, J. M., et al. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.14101329 · Cited by 196 · see citing works
Self-citationDurgam, S., Starace, A., Li, D., Migliore, R., Ruth, A., Németh, G., & Laszlovszky, I. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2013.11.041 · Cited by 192 · see citing works
GOFF, D. C., Posever, T. A., Herz, L. R., Simmons, J., Kletti, N., Lapierre, K. A., Wilner, K. D., Law, C., & Ko, G. N. (1998) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199808000-00009 · Cited by 183 · see citing works
Correll, C. U., Skuban, A., Ouyang, J., Hobart, M., Pfister, S., McQuade, R. D., Nyilas, M., Carson, W. H., Sanchez, R., & Eriksson, H. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.14101275 · Cited by 183 · see citing works
Nasrallah, H. A., Silva, R., Phillips, D., Cucchiaro, J. B., Hsu, J., Xu, J., & Loebel, A. D. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.01.020 · Cited by 144 · see citing works
Extrapyramidal Symptoms in Patients Treated With Risperidone
Simpson, G. M., & Lindenmayer, J. (1997) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199706000-00010 · Cited by 130 · see citing works
Kane, J. M., Cohen, M., Zhao, J., Alphs, L., & Panagides, J. (2010) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181d35d6b · Cited by 126 · see citing works
Lurasidone in the treatment of schizophrenia: a 6-week, placebo-controlled study
Ogasa, M., Kimura, T., Nakamura, M., & Guarino, J. J. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2838-2 · Cited by 114 · see citing works
McEvoy, J. P., Daniel, D. G., Carson, W. H., McQuade, R. D., & Marcus, R. N. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2007.05.002 · Cited by 96 · see citing works
Double-Blind Study of Clozapine Dose Response in Chronic Schizophrenia
Simpson, G. M., Josiassen, R. C., Stanilla, J. K., de León, J., Nair, C., Abraham, G., Odom-White, A., & Turner, R. M. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.11.1744 · Cited by 84 · see citing works
Canuso, C. M., Lindenmayer, J., Kosik‐Gonzalez, C., Turkoz, I., Carothers, J. L., Bossie, C. A., & Schooler, N. R. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.09m05564yel · Cited by 78 · see citing works
Ishigooka, J., Iwashita, S., & Tadori, Y. (2018) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12682 · Cited by 63 · see citing works
Hui, C. L. M., Lam, B. S. T., Lee, E. H. M., Chan, S. K. W., Chang, W. C., Suen, Y. N., & Chen, E. Y. H. (2019) · International Review of Psychiatry · doi:10.1080/09540261.2019.1613965 · Cited by 36 · see citing works
Potkin, S. G., Kimura, T., & Guarino, J. J. (2015) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125315606027 · Cited by 33 · see citing works
Dold, M., Fugger, G., Aigner, M., Lanzenberger, R. R., & Kasper, S. F. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.04.024 · Cited by 30 · see citing works
Increasing antipsychotic dose for non response in schizophrenia
Samara, M. T., Klupp, E., Helfer, B., Rothe, P., Schneider‐Thoma, J., & Leucht, S. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011883.pub2 · Cited by 30 · see citing works
Self-citationIncreasing antipsychotic dose versus switching antipsychotic for non response in schizophrenia
Samara, M. T., Klupp, E., Helfer, B., Rothe, P., Schneider‐Thoma, J., & Leucht, S. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011884.pub2 · Cited by 14 · see citing works
Self-citationClinically Meaningful Gaps Between Clinical Trials and Patient Treatment
Buchanan, R. W., & Carpenter, W. T. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby060 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Andreasen NC, Olsen S. Negative v positive schizo- phrenia. Definition and validation. Arch Gen Psychiatry. 1982;39(7):789-794.
Cited by
Sorted by citations
Correll, C. U., Kim, E., Sliwa, J. K., Hamm, W., Gopal, S., Mathews, M., Venkatasubramanian, R., & Saklad, S. R. (2021) · CNS Drugs · doi:10.1007/s40263-020-00779-5 · Cited by 205 · see citing works
- Authors
- Takeuchi, H., MacKenzie, N. E., Samaroo, D., Agid, O., Remington, G., & Leucht, S.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Dalhousie University (CA)
- Technical University of Munich (DE)
- Corresponding author
- Takeuchi, Hiroyoshi
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-05-16
- Volume
- 46
- Issue
- 6
- Pages
- 1439-1458
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC7707077
- OpenAlex
- W3025481414
- Cited by
- 39
- References
- 42
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 6 · 2021: 11
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Schizophrenia Bulletin (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science
- Japan Agency for Medical Research and Development
- SENSHIN Medical Research Foundation
- Novartis Pharma
- Astellas Foundation for Research on Metabolic Disorders
- Canadian Institutes of Health Research
- Centre for Addiction and Mental Health
- Japanese Society of Clinical Neuropsychopharmacology
- Kyowa
- Janssen
- Meiji Seika Pharma
- Mochida
- Otsuka
- Sumitomo Dainippon Pharma
- Yoshitomiyakuhin
- Acadia
- Boehringer Ingelheim
- DiaMentis
- Janssen-Ortho
- Neurocrine Biosciences
- Syneurx
- HLS Therapeutics
- Research Hospital Fund–Canada Foundation for Innovation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- acute schizophrenia, antipsychotic dosing
- MeSH terms
- Acute Disease, Humans, Schizophrenia, Antipsychotic Agents, Randomized Controlled Trials as Topic, Outcome Assessment, Health Care
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
