Skip to main content

Advertisement

SpringerLink
Log in

Discontinuation of antipsychotics treatment for elderly patients within a specialized behavioural unit: a retrospective review

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Best practice guidelines recommend regular evaluation of antipsychotics in managing behaviours for dementia patients with a view to de-prescribing, given its significant mortality and adverse outcomes (Reus et al. in Am J Psychiatry 173(5):543–546, 2016, Deprescribing Guidelines and Algorithms in https://deprescribing.org/resources/deprescribing-guidelines-algorithms/, 2019). The relationship between the dose of antipsychotic and the probability of discontinuation remains unknown in hospitalized dementia patients. Objectives This study aims to examine the relationship between high dose antipsychotic (greater than 62 mg chlorpromazine equivalent daily dose) and antipsychotics discontinuation in hospitalized dementia patients. Setting Specialized Dementia Behavioral Health Program in Hamilton, Ontario, Canada. Method A retrospective chart review was completed from August to December of 2019. A univariate logistic regression model was applied to antipsychotic doss (in chlorpromazine equivalent) and antipsychotic discontinuation outcome at 60 days (Narayan and Nishtala in Eur J Clin Pharmacol 73(12):1665–1672, 2017). A multivariant model was used to assess potential confounders, including other psychiatric medication exposure and Medicines Comorbidity Index (Luthra in J Gerontol Geriatr Res 4(260):2, 2015). Regression and dose–response models were utilized to identify the threshold dose (maximum daily dose). Main outcome measures Antipsychotic discontinuation at 60 days after the last dose. Results A total of 42 patients were eligible for outcome analysis. High dose antipsychotic was associated with worse discontinuation outcomes in both unadjusted (odds ratio, 0.09; 95% confidence interval, 0.02–0.37; p < 0.01) and adjusted generalized estimation equation models (odds ratio 0.65; 95% confidence interval, 0.59–0.72; p = 0.01). There were no statistically significant associations between baseline comorbidities (Medicines Comorbidity Index) (p = 0.68), mood stabilizer (p = 0.14), benzodiazepines (p = 0.93) and antidepressant exposure (p = 0.68) with antipsychotic discontinuation. The logistic regression model identified 40.7 mg of quetiapine, 1.7 mg of olanzapine and 0.51 mg of risperidone as the threshold dose, balancing sensitivity and specificity. The dose–response model also identified similar doses of 42 mg of quetiapine, 1.76 mg of olanzapine and 0.53 mg of risperidone. Conclusion The use of high dose antipsychotics is associated with worse discontinuation outcomes in hospitalized dementia patients. Therefore, our results suggest not exceeding a daily dose of 50 mg of quetiapine, 1.75 mg of olanzapine and 0.5 mg of risperidone when used for responsive behaviours and reassess the benefits and risks for each patient regularly.

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

Data and code availability

The dataset and the coding template generated and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Public Health Agency of Canada. Dementia in Canada, including Alzheimer’s disease highlights from the Canadian chronic disease surveillance system, Ottawa, Canada. Available from: https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/diseases-conditions/dementia-highlights-canadian-chronic-disease-surveillance/dementia-highlights-canadian-chronic-disease-surveillance.pdf. Accessed 11 Jul 2020.

  2. Canadian Institute of Health Information. Use of antipsychotics among seniors living in long-term care facilities, Canada. Available from: https://secure.cihi.ca/free_products/LTC_AiB_v2_19_EN_web.pdf. Accessed 11 July 2020.

  3. Reus VI, Fochtmann LJ, Eyler AE, Hilty DM, Horvitz-Lennon M, Jibson MD, et al. The american psychiatric association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543–6.

    Article  Google Scholar 

  4. Deyn PPD, Carrasco MM, Deberdt W, Jeandel C, Hay DP, Feldman PD, et al. Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer’s disease. Int J Geriatr Psychiatry. 2004;19(2):115–26.

    Article  Google Scholar 

  5. Street JS, Clark SW, Gannon KS. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities. Arch Gen Psychiatry. 2000;57(10):968.

    Article  CAS  Google Scholar 

  6. Katz IR, Jeste DV, Mintzer JE, Clyde C, Napolitano J, Brecher M. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia. J Clin Psychiatry. 1999;60(2):107–15.

    Article  CAS  Google Scholar 

  7. Zhong KX, Tariot PN, Mintzer J, Minkwitz MC, Devine NA. Quetiapine to treat agitation in dementia: a randomized, double-blind, placebo-controlled study. Curr Alzheimer Res. 2007;4(1):81–93.

    Article  CAS  Google Scholar 

  8. Ballard C, Hanney ML, Theodoulou M, Douglas S, Mcshane R, Kossakowski K, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol. 2009;8(2):151–7.

    Article  CAS  Google Scholar 

  9. Van Leeuwen E, Petrovic M, van Driel ML, De Sutter AI. Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia [Internet]. The Cochrane database of systematic reviews. U.S. National Library of Medicine; 2018 [cited 2020Sep7]. Available from: https://pubmed.ncbi.nlm.nih.gov/29605970/.

  10. Deprescribing Guidelines and Algorithms. Deprescribing.org. 2019. Available from: https://deprescribing.org/resources/deprescribing-guidelines-algorithms/. Accessed 12 Jul 2020.

  11. Reekum RV, Clarke D, Conn D, Herrmann N, Eryavec G, Cohen T, et al. A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia. Int Psychogeriatr. 2002;14(2):197–210.

    Article  Google Scholar 

  12. Patel AN, Lee S, Andrews HF, Pelton GH, Schultz SK, Sultzer DL, et al. Prediction of relapse after discontinuation of antipsychotic treatment in Alzheimer’s disease: the role of hallucinations. Am J Psychiatry. 2017;174(4):362–9.

    Article  Google Scholar 

  13. Ballard CG, Thomas A, Fossey J, Lee L, Jacoby R, Lana MM, et al. A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: the neuropsychiatric inventory median cutoff is a predictor of clinical outcome. J Clin Psychiatry. 2004;65(1):114–9.

    Article  Google Scholar 

  14. Hortwitz GJ, Tariot PN, Mead K, Cox C. Discontinuation of antipsychotics in nursing home patients with dementia. Am J Geriatr Psychiatry. 1995;3(4):290–9.

    Article  Google Scholar 

  15. Luthra AS. A new behavioural assessment tool for patients with major neurocognitve disorders: results of a clinical study. J Gerontol Geriatr Res. 2015;4(260):2.

    Google Scholar 

  16. Narayan SW, Nishtala PS. Development and validation of a Medicines Comorbidity Index for older people. Eur J Clin Pharmacol. 2017;73(12):1665–72.

    Article  Google Scholar 

  17. Gardner DM, Murphy AL, O’donnell H, Centorrino F, Baldessarini RJ. International consensus study of antipsychotic dosing. Am J Psychiatry. 2010;167(6):686–93.

    Article  Google Scholar 

  18. Mast G, Fernandes K, Tadrous M, Martins D, Herrmann N, Gomes T. Persistence of antipsychotic treatment in elderly dementia patients: a retrospective, population-based cohort study. Drugs Real World Outcomes. 2016;3(2):175–82.

    Article  Google Scholar 

  19. Tadrous M, Martins D, Herrmann N, Fernandes K, Yao Z, Singh S. Antipsychotics in the elderly (FINALReport: pharmacoepidemiology unit), Toronto, Canada 2015. Available from: https://odprn.ca/wp-content/uploads/2015/06/Antipsychotic-Pepi-Report.pdf. Accessed 11 Jul 2020.

  20. R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2019.

    Google Scholar 

  21. Sorbi S, Hort J, Erkinjuntti T, Fladby T, Gainotti G, Gurvit H, et al. EFNS-ENS guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol. 2012;19(9):1159–79.

    Article  CAS  Google Scholar 

  22. Alexopoulos GS, Streim J, Carpenter D, Docherty JP. Expert consensus panel for using antipsychotic drugs in older patients. Using antipsychotic agents in older patients. J Clin Psychiatry. 2004;65:5.

    PubMed  Google Scholar 

  23. Davies SJ, Burhan AM, Kim D, Gerretsen P, Graff-Guerrero A, Woo VL, et al. Sequential drug treatment algorithm for agitation and aggression in Alzheimer’s and mixed dementia. J Psychopharmacol. 2018;32(5):509–23.

    Article  CAS  Google Scholar 

  24. Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006;355(15):1525–38.

    Article  CAS  Google Scholar 

  25. Rochon PA, Gruneir A, Gill SS, Wu W, Fischer HD, Bronskill SE, et al. Older men with dementia are at greater risk than women of serious events after initiating antipsychotic therapy. J Am Geriatr Soc. 2013;61(1):55–61.

    Article  Google Scholar 

  26. Maust DT, Kim HM, Seyfried LS, Chiang C, Kavanagh J, Schneider LS, et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia. JAMA Psychiatry. 2015;72(5):438.

    Article  Google Scholar 

  27. Sterke CS, Beeck EFV, Velde NVD, Ziere G, Petrovic M, Looman CWN, et al. New insights: dose-response relationship between psychotropic drugs and falls: a study in nursing home residents with dementia. J Clin Pharmacol. 2012;52(6):947–55.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Joanna Sue and Bhikhu Tejura for their support and critique of the manuscript.

Funding

This study was not funded by any external or internal sources.

Author information

Authors and Affiliations

  1. Department of Pharmacy, St. Peter’s Hospital, Hamilton Health Sciences, Hamilton, ON, Canada

    Raymond LinBin Gao

  2. School of Pharmacy, University of Waterloo, Waterloo, ON, Canada

    Kate Sungeun Lim

  3. Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada

    Atul Sunny Luthra

  4. Schlegal Research Institute in Aging, University of Waterloo, Waterloo, ON, Canada

    Atul Sunny Luthra

Authors
  1. Raymond LinBin Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kate Sungeun Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atul Sunny Luthra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raymond LinBin Gao.

Ethics declarations

Conflicts of interest

All authors declare no conflict of interest in the writing of this manuscript.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, R.L., Lim, K.S. & Luthra, A.S. Discontinuation of antipsychotics treatment for elderly patients within a specialized behavioural unit: a retrospective review. Int J Clin Pharm 43, 212–219 (2021). https://doi.org/10.1007/s11096-020-01135-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-020-01135-9

Keywords

Search

Navigation