Skip to main content
SpringerLink
Log in

Real-world risk of diabetes with antipsychotic use in older New Zealanders: a case-crossover study

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The primary aim was to examine and compare the increased risk of incident diabetes associated with second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs), with and without adjusting for potential confounding factors. The secondary aim was to recalculate the relative risks of diabetes onset using a semi-symmetric bidirectional case-crossover (SSBC) design to adjust for time-trend bias.

Method

Prescription records (2005–2015) of antipsychotics were sourced from New Zealand Pharmaceutical Collections. The first-time diabetes diagnosis was extracted from the National Minimal Dataset. Relative risks (RRs) of diabetes onset were calculated using conditional logistic regression. Time-trend bias was corrected by recalculating the RR using a SSBC design.

Results

Among 645 individuals, the risk of diabetes onset is higher in SGA users (ARR = 8.72, 95% CI = [5.57, 13.67]) compared to FGA users (ARR = 5.68, 95% CI = [3.43, 9.39]). The increased risk of diabetes onset associated with quetiapine is higher (ARR = 7.47, 95% CI = [4.10, 13.62]), compared to haloperidol (ARR = 5.05, 95% CI = [2.91, 8.75]). However, the increased risk of diabetes onset associated with olanzapine (ARR = 2.27, 95% CI = [0.86, 5.98]) is insignificant after adjusting for concomitant use of effect modifiers and other antipsychotic drugs.

Conclusion

The results support that the magnitude of the risk of diabetes is higher with SGA use compared with FGA use, and the risk is higher when co-prescribed. Confounding by indication and time-varying confounders such as body mass index could bias the risk of onset of diabetes. Marginal structural models could provide more precise estimates of the risk of onset of diabetes following exposure to antipsychotics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Stahl SM (1999) Selecting an atypical antipsychotic by combining clinical experience with guidelines from clinical trials. The Journal of clinical psychiatry 60(Suppl 10):31–41

    PubMed  Google Scholar 

  2. Jakovljevic M (2009) New generation vs. first generation antipsychotics debate: pragmatic clinical trials and practice-based evidence. Psychiatr Danub 21(4):446–452

    PubMed  Google Scholar 

  3. Lambert M, Schimmelmann BG, Schacht A, Suarez D, Haro JM, Novick D, Wagner T, Wehmeier PM, Huber CG, Hundemer HP, Dittmann RW, Naber D (2011) Differential 3-year effects of first- versus second-generation antipsychotics on subjective well-being in schizophrenia using marginal structural models. J Clin Psychopharmacol 31(2):226–230. doi:10.1097/JCP.0b013e3182114d21

    Article  CAS  PubMed  Google Scholar 

  4. Buse JB, Cavazzoni P, Hornbuckle K, Hutchins D, Breier A, Jovanovic L (2003) A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United States. J Clin Epidemiol 56(2):164–170

    Article  PubMed  Google Scholar 

  5. Caro JJ, Ward A, Levinton C, Robinson K (2002) The risk of diabetes during olanzapine use compared with risperidone use: a retrospective database analysis. The Journal of clinical psychiatry 63(12):1135–1139

    Article  CAS  PubMed  Google Scholar 

  6. Feldman PD, Hay LK, Deberdt W, Kennedy JS, Hutchins DS, Hay DP, Hardy TA, Hoffmann VP, Hornbuckle K, Breier A (2004) Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a geriatric population in the United States. J Am Med Dir Assoc 5(1):38–46

    Article  PubMed  Google Scholar 

  7. Fuller MA, Shermock KM, Secic M, Grogg AL (2003) Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine. Pharmacotherapy 23(8):1037–1043

    Article  CAS  PubMed  Google Scholar 

  8. Ulcickas Yood M, Delorenze GN, Quesenberry CP Jr, Oliveria SA, Tsai AL, Kim E, Cziraky MJ, McQuade RD, Newcomer JW, L'Italien GJ (2011) Association between second-generation antipsychotics and newly diagnosed treated diabetes mellitus: does the effect differ by dose? BMC psychiatry 11:197. doi:10.1186/1471-244x-11-197

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yood MU, DeLorenze G, Quesenberry CP Jr, Oliveria SA, Tsai AL, Willey VJ, McQuade R, Newcomer J, L’Italien G (2009) The incidence of diabetes in atypical antipsychotic users differs according to agent—results from a multisite epidemiologic study. Pharmacoepidemiol Drug Saf 18(9):791–799. doi:10.1002/pds.1781

    Article  PubMed  Google Scholar 

  10. Montgomery JH, Byerly M, Carmody T, Li B, Miller DR, Varghese F, Holland R (2004) An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia. Control Clin Trials 25(6):598–612. doi:10.1016/j.cct.2004.09.002

    Article  PubMed  Google Scholar 

  11. Peluso MJ, Lewis SW, Barnes TR, Jones PB (2012) Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs. The British journal of psychiatry : the journal of mental science 200(5):387–392. doi:10.1192/bjp.bp.111.101485

    Article  Google Scholar 

  12. Delaney JA, Suissa S (2009) The case-crossover study design in pharmacoepidemiology. Stat Methods Med Res 18(1):53–65. doi:10.1177/0962280208092346

    Article  PubMed  Google Scholar 

  13. Maclure M (1991) The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol 133(2):144–153

    CAS  PubMed  Google Scholar 

  14. Chang CH, Chen HC, Lin JW, Kuo CW, Shau WY, Lai MS (2011) Risk of hospitalization for upper gastrointestinal adverse events associated with nonsteroidal anti-inflammatory drugs: a nationwide case-crossover study in Taiwan. Pharmacoepidemiol Drug Saf 20(7):763–771. doi:10.1002/pds.2140

    Article  CAS  PubMed  Google Scholar 

  15. Schulte PF, Bocxe JT, Doodeman HJ, van Haelst IM, Cohen D (2016) Risk of new-onset diabetes after long-term treatment with clozapine in comparison to other antipsychotics in patients with schizophrenia. J Clin Psychopharmacol 36(2):115–119. doi:10.1097/jcp.0000000000000465

    Article  CAS  PubMed  Google Scholar 

  16. Rubin DM, Kreider AR, Matone M, Huang YS, Feudtner C, Ross ME, Localio AR (2015) Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths. JAMA Pediatr 169(4):e150285. doi:10.1001/jamapediatrics.2015.0285

    Article  PubMed  Google Scholar 

  17. Tandon R (2002) Safety and tolerability: how do newer generation “atypical” antipsychotics compare? The Psychiatric quarterly 73(4):297–311

    Article  PubMed  Google Scholar 

  18. Miron IC, Baroana VC, Popescu F, Ionica F (2014) Pharmacological mechanisms underlying the association of antipsychotics with metabolic disorders. Current health sciences journal 40(1):12–17. doi:10.12865/chsj.40.01.02

    PubMed  Google Scholar 

  19. Nielsen J, Skadhede S, Correll CU (2010) Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naive schizophrenia patients. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 35(9):1997–2004. doi:10.1038/npp.2010.78

    Article  CAS  Google Scholar 

  20. 2004) Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 27(2):596–601

  21. Baker RA, Pikalov A, Tran QV, Kremenets T, Arani RB, Doraiswamy PM (2009) Atypical antipsychotic drugs and diabetes mellitus in the US Food and Drug Administration adverse event database: a systematic Bayesian signal detection analysis. Psychopharmacol Bull 42(1):11–31

    PubMed  Google Scholar 

  22. DuMouchel W, Fram D, Yang X, Mahmoud RA, Grogg AL, Engelhart L, Ramaswamy K (2008) Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968-2004). Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists 20(1):21–31. doi:10.1080/10401230701844612

    Article  Google Scholar 

  23. Navidi W, Weinhandl E (2002) Risk set sampling for case-crossover designs. Epidemiology 13(1):100–105

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Analytical Services, Ministry of Health of New Zealand for providing the datasets and the Research in Pharmacoepidemiology (RiPE) group, School of Pharmacy, University of Otago for providing clinical data management and support. All patient data used in this study are de-identified.

Author information

Authors and Affiliations

  1. School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand

    Prasad S. Nishtala & Te-yuan Chyou

Authors
  1. Prasad S. Nishtala
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Te-yuan Chyou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Prasad S. Nishtala.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Fig S1

(DOCX 69 kb)

Fig S2

(DOCX 33 kb)

Table S1

(DOCX 21 kb)

Table S2

(DOCX 21 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nishtala, P.S., Chyou, Ty. Real-world risk of diabetes with antipsychotic use in older New Zealanders: a case-crossover study. Eur J Clin Pharmacol 73, 233–239 (2017). https://doi.org/10.1007/s00228-016-2158-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-016-2158-2

Keywords

Search

Navigation