Antipsychotics Associated with the Development of Type 2 Diabetes in Antipsychotic-Naïve Schizophrenia Patients
Open accessAbstract
Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population. Reasons for this elevated risk are poorly understood and have not been examined prospectively in antipsychotic-naïve, first-episode patients. This study aims to determine which antipsychotics are associated with diabetes development in antipsychotic-naïve schizophrenia patients. All antipsychotic-naïve patients diagnosed with schizophrenia in Denmark between 01 January 1997 and 31 December 2004, followed until 31 December 2007, allowing for >or=3 years follow-up, unless death or diabetes onset occurred. Risk factors for the time to diabetes onset were assessed, including antipsychotics taken for at least 180 defined daily doses in the first year after first antipsychotic prescription ('initial treatment'). Risk factors for diabetes incidence were assessed, including antipsychotic use within 3 months before diabetes onset or study end ('current treatment'). Of 7139 patients, followed for 6.6 years (47,297 patient years), 307 developed diabetes (annual incidence rate: 0.65%). Time to diabetes onset was significantly shorter in patients with higher age (hazard ratio (HR): 1.03, confidence interval (CI): 1.02-1.03) and those with 'initial' treatment of olanzapine (HR: 1.41, CI: 1.09-1.83), mid-potency first-generation antipsychotics (FGAs) (HR: 1.60, CI: 1.07-2.39), antihypertensive (HR: 1.87, CI: 1.13-3.09), or lipid-lowering drugs (HR: 4.67, CI: 2.19-10.00). Significant factors associated with diabetes within 3 month of its development included treatment with low-potency FGAs (odds ratio (OR): 1.52, CI: 1.14-2.02), olanzapine (OR: 1.44, CI: 1.98-1.91), and clozapine (OR: 1.67, CI: 1.14-2.46), whereas aripiprazole was associated with lower diabetes risk (OR: 0.51, CI: 0.33-0.80). In addition to general diabetes risk factors, such as age, hypertension, and dyslipidemia, diabetes is promoted in schizophrenia patients by initial and current treatment with olanzapine and mid-potency FGAs, as well as by current treatment with or low-potency first-generation antipsychotics and clozapine, whereas current aripiprazole treatment reduced diabetes risk. Patients discontinuing olanzapine or mid-potency FGA had no increased risk of diabetes compared with patient not treated with the drugs at anytime.
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Variations in the risk for glucose abnormalities are evident in the literature, with the highest risk being associated with clozapine, olanzapine and quetiapine in carefully designed studies.
“Variations in the risk for glucose abnormalities are evident in the literature, with the highest risk being associated with clozapine, olanzapine and quetiapine in carefully designed studies 25,34,35 .”
From Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta‐analysis (2016) · cites this paper as [34]
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Jafari, S., Fernandez, F., & Huang, X. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07590.x · Cited by 76 · see citing works
Nielsen, J., Kane, J. M., & Correll, C. U. (2012) · Bipolar Disorders · doi:10.1111/bdi.12018 · Cited by 74 · see citing works
Self-citationSchizophrenia and type 2 diabetes mellitus
Mamakou, V., Thanopoulou, A. C., Gonidakis, F., Tentolouris, N., & Kontaxakis, V. P. (2018) · Psychiatriki · doi:10.22365/jpsych.2018.291.64 · Cited by 72 · see citing works
Comparative Tolerability of Dopamine D2/3 Receptor Partial Agonists for Schizophrenia
Keks, N. A., Hope, J., Schwartz, D., McLennan, H., Copolov, D., & Meadows, G. N. (2020) · CNS Drugs · doi:10.1007/s40263-020-00718-4 · Cited by 71 · see citing works
Polcwiartek, C., Sneider, B., Graff, C., Taylor, D. M., Meyer, J. M., Kanters, J. K., & Nielsen, J. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4024-9 · Cited by 70 · see citing works
Self-citationThe side effect profile of Clozapine in real world data of three large mental health hospitals
Iqbal, E., Govind, R., Romero, A., Dzahini, O., Broadbent, M. T. M., Stewart, R. J., Smith, T. D., Kim, C.-H., Werbeloff, N., MacCabe, J. H., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0243437 · Cited by 64 · see citing works
Characteristics and predictors of long-term institutionalization in patients with schizophrenia
Uggerby, P., Nielsen, R. E., Correll, C. U., & Nielsen, J. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.03.001 · Cited by 64 · see citing works
Self-citationWu, L.-T. T., Ghitza, U. E., Batch, B. C., Pencina, M. J., Rojas, L. F., Goldstein, B. A., Schibler, T., Dunham, A. A., Rusincovitch, S. A., & Brady, K. T. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.09.003 · Cited by 60 · see citing works
Cardiovascular safety of antipsychotics: a clinical overview
Polcwiartek, C., Kragholm, K. H., Schjerning, O., Graff, C., & Nielsen, J. (2016) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2016.1161021 · Cited by 59 · see citing works
Self-citationPetrikis, P., Tigas, S. K., Tzallas, A. T., Papadopoulos, I. A., Skapinakis, P., & Mavreas, V. G. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.07.041 · Cited by 58 · see citing works
The prevalence of metabolic syndrome in people with severe mental illness: a mediation analysis
Carrà, G., Bartoli, F., Carretta, D., Crocamo, C., Bozzetti, A., Clerici, M., & Bebbington, P. (2014) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-014-0835-y · Cited by 56 · see citing works
Foley, D., Mackinnon, A., Watts, G., Shaw, J., Magliano, D., Castle, D., McGrath, J., Waterreus, A., Morgan, V., & Galletly, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082606 · Cited by 52 · see citing works
A review of dopamine agonist therapy in type 2 diabetes and effects on cardio-metabolic parameters
Lamos, E. M., Levitt, D. L., & Munir, K. M. (2015) · Primary care diabetes · doi:10.1016/j.pcd.2015.10.008 · Cited by 51 · see citing works
Citrome, L., Kalsekar, I. D., Baker, R. A., & Hebden, T. (2014) · Current Medical Research and Opinion · doi:10.1185/03007995.2014.908280 · Cited by 50 · see citing works
Yood, M. U., DeLorenze, G. N., Quesenberry, C. P., Oliveria, S. A., Tsai, A., Kim, E., Cziraky, M. J., McQuade, R. D., Newcomer, J. W., & L'Italien, G. J. (2011) · BMC Psychiatry · doi:10.1186/1471-244x-11-197 · Cited by 50 · see citing works
Correll, C. U., Kishimoto, T., & Kane, J. M. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.2/ccorrell · Cited by 48 · see citing works
Self-citationAugmenting Clozapine With Sertindole
Nielsen, J., Emborg, C., Gydesen, S., Dybbro, J., Aagaard, J., Haderup, K., Glyngdal, P., Fabricius, S., Thode, D., Lublin, H., et al. (2012) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318248dfb8 · Cited by 44 · see citing works
Self-citationNyboe, L., Vestergaard, C. H., Moeller, M. K., Lund, H., & Videbech, P. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.07.053 · Cited by 40 · see citing works
Predictors of type 2 diabetes in a nationally representative sample of adults with psychosis
Foley, D. L., Mackinnon, A. J., Morgan, V. A., Watts, G. F., McGrath, J. J., Castle, D. J., Waterreus, A. J., & Galletly, C. A. (2014) · World Psychiatry · doi:10.1002/wps.20130 · Cited by 39 · see citing works
Ko, C., & Liu, Y. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.08.003 · Cited by 38 · see citing works
Psychological and Psychopharmacological Interventions in Psychocardiology
Kahl, K. G., Stapel, B., & Correll, C. U. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.831359 · Cited by 39 · see citing works
Self-citationUnrecognised myocardial infarction in patients with schizophrenia
Nielsen, J., Juel, J., Alzuhairi, K., Friis, R. B., Graff, C., Kanters, J. K., & Jensen, S. E. (2015) · Acta Neuropsychiatrica · doi:10.1017/neu.2014.41 · Cited by 37 · see citing works
Self-citationPolcwiartek, C., Vang, T., Bruhn, C. H., Hashemi, N., Rosenzweig, M., & Nielsen, J. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4411-x · Cited by 37 · see citing works
Self-citationAdherence to Guidelines for Glucose Assessment in Starting Second-Generation Antipsychotics
Raebel, M. A., Penfold, R. B., McMahon, A. W., Reichman, M. E., Shetterly, S. M., Goodrich, G. K., Andrade, S., Correll, C. U., & Gerhard, T. (2014) · PEDIATRICS · doi:10.1542/peds.2014-0828 · Cited by 37 · see citing works
Self-citationDo antipsychotics increase diabetes risk in children and adolescents?
Galling, B., & Correll, C. U. (2014) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2015.979150 · Cited by 35 · see citing works
Self-citationKato, Y., Umetsu, R., Abe, J., Ueda, N., Nakayama, Y., Kinosada, Y., & Nakamura, M. (2015) · Journal of Pharmaceutical Health Care and Sciences · doi:10.1186/s40780-015-0015-6 · Cited by 34 · see citing works
22q11.2 microdeletion and increased risk for type 2 diabetes
Van, L., Heung, T., Malecki, S. L., Fenn, C., Tyrer, A. E., Sanches, M., Chow, E. W. C., Boot, E., Corral, M. R., Dash, S., et al. (2020) · EClinicalMedicine · doi:10.1016/j.eclinm.2020.100528 · Cited by 31 · see citing works
Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Patients With Schizophrenia
Nielsen, J., Røge, R., Pristed, S. G., Viuff, A. G., Ullum, H., Thørner, L. W., Werge, T. M., & Vang, T. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu118 · Cited by 30 · see citing works
Self-citationFoley, D. L., Mackinnon, A. J., Morgan, V. A., Watts, G. F., Castle, D. J., Waterreus, A. J., & Galletly, C. A. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00276-x · Cited by 29 · see citing works
Welie, H., Derks, E. M., Verweij, K. H. W., de Valk, H. W., Kahn, R. S., & Cahn, W. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.11.011 · Cited by 29 · see citing works
CNR1 Gene and Risk of the Metabolic Syndrome in Patients With Schizophrenia
Yu, W., Binder, M. D., Moons, T., Claes, S. J., Correll, C. U., & van Winkel, R. (2013) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318283925e · Cited by 29 · see citing works
Self-citationVolpato, A. M., Zugno, A. I., & Quevedo, J. (2013) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2012-1052 · Cited by 29 · see citing works
Common familial risk factors for schizophrenia and diabetes mellitus
Foley, D. L., Mackinnon, A. J., Morgan, V. A., Watts, G. F., Castle, D. J., Waterreus, A. J., & Galletly, C. A. (2015) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867415595715 · Cited by 28 · see citing works
Inada, K., Oshibuchi, H., Ishigooka, J., & Nishimura, K. (2018) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000904 · Cited by 28 · see citing works
Nielsen, R. E., Laursen, M. F., Vernal, D. L., Bisgaard, C., Jakobsen, H. N., Steinhausen, H., & Correll, C. U. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.04.023 · Cited by 27 · see citing works
Self-citationHeal, D. J., Gosden, J., Jackson, H. C., Cheetham, S. C., & Smith, S. L. (2012) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25761-2_6 · Cited by 26 · see citing works
Psychopharmacologic Treatment of Psychosis in Children and Adolescents
Kranzler, H. N., & Cohen, S. D. (2013) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2013.06.002 · Cited by 27 · see citing works
Hematological clozapine monitoring with a point-of-care device: A randomized cross-over trial
Nielsen, J., Thode, D., Stenager, E. N., Andersen, K. Ø., Sondrup, U., Hansen, T. N., Munk, A. M., Lykkegaard, S. E., Gosvig, A., Petrov, I., et al. (2011) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2011.10.001 · Cited by 27 · see citing works
Self-citationCohen, D., & Binder, M. D. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.94 · Cited by 27 · see citing works
Kishi, T., Fujita, K., Furukawa, O., Suzuki, T., Moriwaki, M., Nitta, M., Hattori, M., Tsunoka, T., Chekuri, R., Kane, J. M., et al. (2012) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2012.10.007 · Cited by 25 · see citing works
Self-citationNemani, K., Greene, M., Ulloa, M., Vincenzi, B., Copeland, P., Al-Khadari, S., & Henderson, D. (2017) · Clinical Schizophrenia and Related Psychoses · doi:10.3371/csrp.knmg.111717 · Cited by 21 · see citing works
Hu, S., Yao, M., Peterson, B. S., Xu, D., Hu, J., Tang, J., Fan, B., Liao, Z., Yuan, T., Li, Y., et al. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3073-1 · Cited by 25 · see citing works
Crespo‐Facorro, B., Pelayo‐Terán, J. M., & Son, J. M.-V. (2016) · Neurology and Therapy · doi:10.1007/s40120-016-0050-8 · Cited by 25 · see citing works
Kammer, J., Hosler, A. S., Leckman‐Westin, E., DiRienzo, G., & Osborn, C. Y. (2015) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2015.10.017 · Cited by 24 · see citing works
Uncovering the source of new benzodiazepine prescriptions in community‐dwelling older adults’
Halme, A. S., Béland, S., Préville, M., & Tannenbaum, C. (2012) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.3818 · Cited by 24 · see citing works
Ingimarsson, O., MacCabe, J. H., Haraldsson, M. H., Jónsdóttir, H., & Sigurðsson, E. (2017) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2017.1334821 · Cited by 24 · see citing works
Zhang, R., Hao, W., Pan, M., Wang, C., Zhang, X., Chen, D. C., Xiu, M. H., Yang, F. D., Kosten, T. R., & Zhang, X. Y. (2011) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1220 · Cited by 24 · see citing works
Polygenic risk for type 2 diabetes mellitus among individuals with psychosis and their relatives
Padmanabhan, J. L., Nanda, P., Tandon, N., Mothi, S. S., Bolo, N. R., McCarroll, S. A., Clementz, B. A., Gershon, E. S., Pearlson, G. D., Sweeney, J. A., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.02.015 · Cited by 23 · see citing works
Persico, M., Abbruzzese, C., Matteoni, S., Matarrese, P., Campana, A. M., Villani, V., Pace, A., & Paggi, M. G. (2022) · Cells · doi:10.3390/cells11020263 · Cited by 22 · see citing works
Polcwiartek, C., Kragholm, K. H., Rohde, C., Hashemi, N., Vang, T., & Nielsen, J. (2017) · Diabetologia · doi:10.1007/s00125-017-4320-5 · Cited by 22 · see citing works
Self-citationEffect of Atypical Antipsychotics on Fetal Growth: Is the Placenta Involved?
Raha, S., Taylor, V. H., & Holloway, A. C. (2012) · Journal of Pregnancy · doi:10.1155/2012/315203 · Cited by 21 · see citing works
Cuevas, C. D. L., Sanz, E. J., Gross, J. A., Correll, C. U., Verdoux, H., Lally, J., de Filippis, R., Schulte, P. F. J., Molden, E., Arrojo, M., et al. (2023) · Schizophrenia Research · doi:10.1016/j.schres.2023.11.010 · Cited by 21 · see citing works
Self-citationOral Health Is a Challenging Problem for Patients with Schizophrenia: A Narrative Review
Denis, F., Pelletier, J., Chauvet‐Gélinier, J., Rude, N., & Trojak, B. (2018) · Iranian Journal of Psychiatry and Behavioral Sciences · doi:10.5812/ijpbs.8062 · Cited by 20 · see citing works
Pai, N. B., Laidlaw, M., & Vella, S. (2012) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2012.01854.x · Cited by 20 · see citing works
Use of aripiprazole for delirium in the elderly: a short review
Kirino, E. (2014) · Psychogeriatrics · doi:10.1111/psyg.12088 · Cited by 20 · see citing works
Correll, C. U., & Nielsen, J. (2010) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2010.01610.x · Cited by 20 · see citing works
Self-citationJakobsen, K. D., Bruhn, C. H., Pagsberg, A. K., Fink‐Jensen, A., & Nielsen, J. (2016) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000548 · Cited by 19 · see citing works
Self-citation
- Authors
- Nielsen, J., Skadhede, S., & Correll, C. U.
- Affiliations
- Aarhus University Hospital (DK)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Nielsen, Jimmi
- Venue
- Neuropsychopharmacology
- Published
- 2010-06-02
- Volume
- 35
- Issue
- 9
- Pages
- 1997-2004
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055629
- OpenAlex
- W2009405599
- Cited by
- 207
- References
- 46
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 11 · 2021: 9 · 2020: 10 · 2019: 12 · 2018: 15 · 2017: 12 · 2016: 14 · 2015: 25 · 2014: 16 · 2013: 17 · 2012: 20
- FWCI
- 13.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- type 2 diabetes, schizophrenia, antipsychotic drugs, antipsychotic-naive patients, first-episode schizophrenia, olanzapine, clozapine, aripiprazole, typical antipsychotics, antihypertensive drugs, lipid-lowering drugs, diabetes risk factors, diabetes incidence
- MeSH terms
- Olanzapine, Adult, Antihypertensive Agents, Benzodiazepines, Denmark, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Humans, Male, Retrospective Studies, Risk Factors, Schizophrenia, Time Factors, Antipsychotic Agents, Cohort Studies, Incidence, Confidence Intervals
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