Antipsychotic Use and Bloodstream Infections Among Adult Patients With Chronic Obstructive Pulmonary Disease: A Cohort Study

Augusto Ferraris, MD; Belén Blasco, MD; Nicolás Tentoni, MD; Facundo Del Olmo, MD; Tomás Barrera, MD; Federico Angriman, MD, MPH; Alejandro G. Szmulewicz, MD, MPH

J Clin Psychiatry 2021;82(3):20m13516

ABSTRACT

Objective: Mounting evidence suggests that antipsychotics may have immunomodulatory effects, but their impact on disseminated infections remains unknown. This study thus sought to estimate the effect of antipsychotic treatment on the occurrence of bloodstream infection during long-term follow-up in adult patients with chronic obstructive pulmonary disease.

Methods: This retrospective cohort study, with new user and active comparator design, included adult patients seen from January 2008 to June 2018 in a tertiary teaching hospital in Buenos Aires, Argentina. New users of antipsychotic drugs were compared to new users of any benzodiazepine. The primary outcome of interest was incident bloodstream infection at 1 year of follow-up. Propensity score methods and a Cox proportional hazards model were used to adjust for baseline confounding.

Results: A total of 923 patients were included in the present analysis. Mean (SD) age was 75.0 (9.8) years, and 51.9% of patients were female. The cumulative incidence of bloodstream infections at 1 year was 6.0% and 2.3% in the antipsychotic and benzodiazepine groups, respectively. Antipsychotic use was associated with a higher risk of bloodstream infections during the first year of follow-up (hazard ratio [HR] = 2.41; 95% CI, 1.13 to 5.14) compared to benzodiazepine use. Antipsychotics with high dopamine receptor affinity presented greater risk than less selective agents (HR = 5.20; 95% CI, 1.53 to 17.67).

Conclusions: Antipsychotic use is associated with bloodstream infections during the first year of follow-up in adult patients with chronic obstructive pulmonary disease. Further studies are warranted to confirm our findings and evaluate this effect in a broader population of patients.

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References (35)

Buist AS, McBurnie MA, Vollmer WM, et al; BOLD Collaborative Research Group. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet. 2007;370(9589):741–750. PubMed CrossRef
Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet. 2007;370(9589):765–773. PubMed CrossRef
Jones DR, Macias C, Barreira PJ, et al. Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness. Psychiatr Serv. 2004;55(11):1250–1257. PubMed CrossRef
Yohannes AM, Alexopoulos GS. Depression and anxiety in patients with COPD. Eur Respir Rev. 2014;23(133):345–349. PubMed CrossRef
Szmulewicz AG, Angriman F, Pedroso FE, et al. Long-term antipsychotic use and major cardiovascular events: a retrospective cohort study. J Clin Psychiatry. 2017;78(8):e905–e912. PubMed CrossRef
Ferraris A, Szmulewicz AG, Vazquez FJ, et al. Antipsychotic use among adult outpatients and venous thromboembolic disease: a retrospective cohort study. J Clin Psychopharmacol. 2017;37(4):405–411. PubMed CrossRef
Szmulewicz AG, Ferraris A, Rodriguez A, et al. All-cause mortality in older adults with affective disorders and dementia under treatment with antipsychotic drugs: a matched-cohort study. Psychiatry Res. 2018;265(265):82–86. PubMed
van Strien AM, Souverein PC, Keijsers CJPW, et al. Association between urinary tract infections and antipsychotic drug use in older adults. J Clin Psychopharmacol. 2018;38(4):296–301. PubMed CrossRef
Kuo CJ, Yang SY, Liao YT, et al. Second-generation antipsychotic medications and risk of pneumonia in schizophrenia. Schizophr Bull. 2013;39(3):648–657. PubMed CrossRef
Schneider-Thoma J, Efthimiou O, Bighelli I, et al. Second-generation antipsychotic drugs and short-term somatic serious adverse events: a systematic review and meta-analysis. Lancet Psychiatry. 2019;6(9):753–765. PubMed CrossRef
Zhang XY, Zhou DF, Cao LY, et al. Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J Clin Psychiatry. 2004;65(7):940–947. PubMed CrossRef
de Witte L, Tomasik J, Schwarz E, et al. Cytokine alterations in first-episode schizophrenia patients before and after antipsychotic treatment. Schizophr Res. 2014;154(1-3):23–29. PubMed CrossRef
Chen ML, Wu S, Tsai TC, et al. Regulation of macrophage immune responses by antipsychotic drugs. Immunopharmacol Immunotoxicol. 2013;35(5):573–580. PubMed CrossRef
Wang MT, Tsai CL, Lin CW, et al. Association between antipsychotic agents and risk of acute respiratory failure in patients with chronic obstructive pulmonary disease. JAMA Psychiatry. 2017;74(3):252–260. PubMed CrossRef
Laursen TM, Munk-Olsen T, Agerbo E, et al. Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder. Arch Gen Psychiatry. 2009;66(7):713–720. PubMed CrossRef
Inghammar M, Engström G, Ljungberg B, et al. Increased incidence of invasive bacterial disease in chronic obstructive pulmonary disease compared to the general population: a population based cohort study. BMC Infect Dis. 2014;14(1):163. PubMed CrossRef
Khorrami F, Ahmadi M, Sheikhtaheri A. Evaluation of SNOMED CT content coverage: a systematic literature review. Stud Health Technol Inform. 2018;248:212–219. PubMed
von Elm E, Altman DG, Egger M, et al; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–1457. PubMed CrossRef
Vijay A, Becker JE, Ross JS. Patterns and predictors of off-label prescription of psychiatric drugs. PLoS One. 2018;13(7):e0198363. PubMed CrossRef
Carnes M, Howell T, Rosenberg M, et al. Physicians vary in approaches to the clinical management of delirium. J Am Geriatr Soc. 2003;51(2):234–239. PubMed CrossRef
VanderWeele TJ. Principles of confounder selection. Eur J Epidemiol. 2019;34(3):211–219. PubMed CrossRef
Cole SR, Hernán MA. Constructing inverse probability weights for marginal structural models. Am J Epidemiol. 2008;168(6):656–664. PubMed CrossRef
Sattar N, Preiss D. Reverse causality in cardiovascular epidemiological research: more common than imagined? Circulation. 2017;135(24):2369–2372. PubMed CrossRef
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496–509. CrossRef
VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med. 2017;167(4):268–274. PubMed CrossRef
Drzyzga L, Obuchowicz E, Marcinowska A, et al. Cytokines in schizophrenia and the effects of antipsychotic drugs. Brain Behav Immun. 2006;20(6):532–545. PubMed CrossRef
Basu S, Dasgupta PS. Dopamine, a neurotransmitter, influences the immune system. J Neuroimmunol. 2000;102(2):113–124. PubMed CrossRef
Steele TA, Brahmi Z. Chlorpromazine inhibits human natural killer cell activity and antibody-dependent cell-mediated cytotoxicity. Biochem Biophys Res Commun. 1988;155(2):597–602. PubMed CrossRef
Stapel B, Sieve I, Falk CS, et al. Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells. J Psychiatr Res. 2018;105:95–102. PubMed CrossRef
Calverley PMA, Anderson JA, Celli B, et al; TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356(8):775–789. PubMed CrossRef
Govind R, Fonseca de Freitas D, Pritchard M, et al. Clozapine treatment and risk of COVID-19 infection: retrospective cohort study. Br J Psychiatry. 2020;1–7. PubMed CrossRef
Stoecker ZR, George WT, O’Brien JB, et al. Clozapine usage increases the incidence of pneumonia compared with risperidone and the general population: a retrospective comparison of clozapine, risperidone, and the general population in a single hospital over 25 months. Int Clin Psychopharmacol. 2017;32(3):155–160. PubMed CrossRef
Chang CK, Chen PH, Pan CH, et al. Antipsychotic medications and the progression of upper respiratory infection to pneumonia in patients with schizophrenia. Schizophr Res. 2020;222:327–334. PubMed CrossRef
Angriman F, Masse M-H, Adhikari NKJ. Defining standard of practice: pros and cons of the usual care arm. Curr Opin Crit Care. 2019;25(5):498–504. PubMed CrossRef
Huitfeldt A, Hernan MA, Kalager M, et al. Comparative effectiveness research using observational data: active comparators to emulate target trials with inactive comparators. EGEMS (Wash DC). 2016;4(1):1234. PubMed