Introduction
For the pharmacotherapy of delirium in elderly adults who are hospitalized, atypical antipsychotics are used. Currently, there is insufficient evidence on the effectiveness of this treatment in low complexity units.

Methods
We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE/PubMed, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis, and generated a summary of findings table using the GRADE approach.

Results and conclusions
We identified 13 systematic reviews that included three randomized trials. We concluded that the use of atypical antipsychotics in hospitalized patients likely increases the risk of mortality compared to placebo and could decrease the response rate associated with reducing the risk of adverse effects. Furthermore, using atypical antipsychotics probably results in low or no difference in the severity of delirium.

Authors: Daniza Belén Bilicic Ubierna[1], Nicolás Cattarinich Schiffrin[1], Daniela Coronel Cárdenas[1], Rubén Soto Munizaga[2], José Miguel Bernucci Piedra[2]

Affiliation:
[1] Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile
[2] Departamento de Medicina interna, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile

E-mail: dcoronelc@uft.edu

Author address:
[1] Avenida Pedro de Valdivia 1509
Santiago, Chile

Citation: Bilicic Ubierna DB, Cattarinich Schiffrin N, Coronel Cárdenas D, Soto Munizaga R, Bernucci Piedra JM. Atypical antipsychotics for delirium in hospitalized patients. Medwave 2021;21(04):e8168 doi: 10.5867/medwave.2021.04.8168

Submission date: 27/11/2020

Acceptance date: 22/3/2021

Publication date: 7/5/2021

Origin: Not commissioned.

Type of review: Externally peer-reviewed by two reviewers, double-blind.

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1. Rozman, C. "Farreras: Medicina Interna" 13 era. edición. Doyma, Madrid, 1995.
2. Kim MS, Rhim HC, Park A, Kim H, Han KM, Patkar AA, et al. Comparative efficacy and acceptability of pharmacological interventions for the treatment and prevention of delirium: A systematic review and network meta-analysis. J Psychiatr Res. 2020 Jun;125:164-176. | CrossRef | PubMed |
3. Neufeld KJ, Needham DM, Oh ES, Wilson LM, Nikooie R, Zhang A, et al. Antipsychotics for the Prevention and Treatment of Delirium [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2019 Sep. Report No.: 19-EHC019-EF. | PubMed |
4. Nikooie R, Neufeld KJ, Oh ES, Wilson LM, Zhang A, Robinson KA, et al. Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review. Ann Intern Med. 2019 Oct 1;171(7):485-495. | CrossRef | PubMed |
5. Rivière J, van der Mast RC, Vandenberghe J, Van Den Eede F. Efficacy and Tolerability of Atypical Antipsychotics in the Treatment of Delirium: A Systematic Review of the Literature. Psychosomatics. 2019 Jan-Feb;60(1):18-26. | CrossRef | PubMed |
6. Wu YC, Tseng PT, Tu YK, Hsu CY, Liang CS, Yeh TC, et al. Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis. JAMA Psychiatry. 2019 May 1;76(5):526-535. | CrossRef | PubMed |
7. Burry L, Mehta S, Perreault MM, Luxenberg JS, Siddiqi N, Hutton B, et al. Antipsychotics for treatment of delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2018 Jun 18;6(6):CD005594. | CrossRef | PubMed |
8. Kishi T, Hirota T, Matsunaga S, Iwata N. Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2016 Jul;87(7):767-74. | CrossRef | PubMed |
9. Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc. 2016 Apr;64(4):705-14. | CrossRef | PubMed |
10. Friedman JI, Soleimani L, McGonigle DP, Egol C, Silverstein JH. Pharmacological treatments of non-substance-withdrawal delirium: a systematic review of prospective trials. Am J Psychiatry. 2014 Feb;171(2):151-9. | CrossRef | PubMed |
11. Hawkins SB, Bucklin M, Muzyk AJ. Quetiapine for the treatment of delirium. J Hosp Med. 2013 Apr;8(4):215-20. | CrossRef | PubMed |
12. Wang HR, Woo YS, Bahk WM. Atypical antipsychotics in the treatment of delirium. Psychiatry Clin Neurosci. 2013 Jul;67(5):323-31. | CrossRef | PubMed |
13. Meagher DJ, McLoughlin L, Leonard M, Hannon N, Dunne C, O'Regan N. What do we really know about the treatment of delirium with antipsychotics? Ten key issues for delirium pharmacotherapy. Am J Geriatr Psychiatry. 2013 Dec;21(12):1223-38. | CrossRef | PubMed |
14. Flaherty JH, Gonzales JP, Dong B. Antipsychotics in the treatment of delirium in older hospitalized adults: a systematic review. J Am Geriatr Soc. 2011 Nov;59 Suppl 2:S269-76. | CrossRef | PubMed |
15. Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, et al. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jan 1;177(1):34-42. | CrossRef | PubMed |
16. Tahir TA, Eeles E, Karapareddy V, Muthuvelu P, Chapple S, Phillips B, et al. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. J Psychosom Res. 2010 Nov;69(5):485-90. | CrossRef | PubMed |
17. Hu, Hua, Deng, Wei, Yang, Hui. A prospective random control study comparison of olanzapine and haloperidol in senile delirium. Chongqing Med J. 2004;8:1234-1237. [Internet] | Link |
18. Hu, H, Deng, W, Yang, H, Liu, Y. Olanzapine and haloperidol for senile delirium: A randomized controlled observation. Chinese Journal of Clinical Rehabilitation. 2006;10:188-190. [Internet] | Link |
19. National Institute for Health and Clinical Excellence. Delirium: diagnosis, prevention and management. (Clinical guideline 103) 2010; 341: c3704. [Internet] | Link |

Rozman, C. "Farreras: Medicina Interna" 13 era. edición. Doyma, Madrid, 1995.

Kim MS, Rhim HC, Park A, Kim H, Han KM, Patkar AA, et al. Comparative efficacy and acceptability of pharmacological interventions for the treatment and prevention of delirium: A systematic review and network meta-analysis. J Psychiatr Res. 2020 Jun;125:164-176. | CrossRef | PubMed |

Neufeld KJ, Needham DM, Oh ES, Wilson LM, Nikooie R, Zhang A, et al. Antipsychotics for the Prevention and Treatment of Delirium [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2019 Sep. Report No.: 19-EHC019-EF. | PubMed |

Nikooie R, Neufeld KJ, Oh ES, Wilson LM, Zhang A, Robinson KA, et al. Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review. Ann Intern Med. 2019 Oct 1;171(7):485-495. | CrossRef | PubMed |

Rivière J, van der Mast RC, Vandenberghe J, Van Den Eede F. Efficacy and Tolerability of Atypical Antipsychotics in the Treatment of Delirium: A Systematic Review of the Literature. Psychosomatics. 2019 Jan-Feb;60(1):18-26. | CrossRef | PubMed |

Wu YC, Tseng PT, Tu YK, Hsu CY, Liang CS, Yeh TC, et al. Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis. JAMA Psychiatry. 2019 May 1;76(5):526-535. | CrossRef | PubMed |

Burry L, Mehta S, Perreault MM, Luxenberg JS, Siddiqi N, Hutton B, et al. Antipsychotics for treatment of delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2018 Jun 18;6(6):CD005594. | CrossRef | PubMed |

Kishi T, Hirota T, Matsunaga S, Iwata N. Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2016 Jul;87(7):767-74. | CrossRef | PubMed |

Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc. 2016 Apr;64(4):705-14. | CrossRef | PubMed |

Friedman JI, Soleimani L, McGonigle DP, Egol C, Silverstein JH. Pharmacological treatments of non-substance-withdrawal delirium: a systematic review of prospective trials. Am J Psychiatry. 2014 Feb;171(2):151-9. | CrossRef | PubMed |

Hawkins SB, Bucklin M, Muzyk AJ. Quetiapine for the treatment of delirium. J Hosp Med. 2013 Apr;8(4):215-20. | CrossRef | PubMed |

Wang HR, Woo YS, Bahk WM. Atypical antipsychotics in the treatment of delirium. Psychiatry Clin Neurosci. 2013 Jul;67(5):323-31. | CrossRef | PubMed |

Meagher DJ, McLoughlin L, Leonard M, Hannon N, Dunne C, O'Regan N. What do we really know about the treatment of delirium with antipsychotics? Ten key issues for delirium pharmacotherapy. Am J Geriatr Psychiatry. 2013 Dec;21(12):1223-38. | CrossRef | PubMed |

Flaherty JH, Gonzales JP, Dong B. Antipsychotics in the treatment of delirium in older hospitalized adults: a systematic review. J Am Geriatr Soc. 2011 Nov;59 Suppl 2:S269-76. | CrossRef | PubMed |

Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, et al. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jan 1;177(1):34-42. | CrossRef | PubMed |

Tahir TA, Eeles E, Karapareddy V, Muthuvelu P, Chapple S, Phillips B, et al. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. J Psychosom Res. 2010 Nov;69(5):485-90. | CrossRef | PubMed |

Hu, Hua, Deng, Wei, Yang, Hui. A prospective random control study comparison of olanzapine and haloperidol in senile delirium. Chongqing Med J. 2004;8:1234-1237. [Internet] | Link |

Hu, H, Deng, W, Yang, H, Liu, Y. Olanzapine and haloperidol for senile delirium: A randomized controlled observation. Chinese Journal of Clinical Rehabilitation. 2006;10:188-190. [Internet] | Link |

National Institute for Health and Clinical Excellence. Delirium: diagnosis, prevention and management. (Clinical guideline 103) 2010; 341: c3704. [Internet] | Link |