Antipsychotic, and benzodiazepine and benzodiazepine-related drug use is associated with an increased risk of pneumonia in older adults. |
Only a few studies have been performed on the association between antidepressant or antiepileptic use and pneumonia. More studies are needed to verify the few findings of drug use and risk of pneumonia. |
The current AGS Beers Criteria and STOPP/START Criteria have no specific comment on avoidance of psychotropics or groups of psychotropics due to the risk of pneumonia in older adults. However, avoiding them is advised based on evidence of other adverse events. |
1 Introduction
2 Literature Search Methods
3 Prevalence and Indication of Psychotropics
3.1 Antipsychotics
3.2 Benzodiazepines and Benzodiazepine-Related Drugs
3.3 Antidepressants
4 Prevalence and Indications of Antiepileptics
5 Psychotropic Use and Risk of Pneumonia
5.1 Antipsychotics
Study, year, country and data source | Study type | Participants (sample size) | Age (years) | Accommodation | Confounders adjusted for | Population | Drugs investigated | Exposure definition | Comparison group | Outcome or case definition | Risk of pneumonia |
---|---|---|---|---|---|---|---|---|---|---|---|
Cohort studies | |||||||||||
Herzig et al. [122], 2017, USA, hospital medical records | Cohort | Exposed (n = 10,377), unexposed (n = 136,175) during hospitalization | Exposed median age 69, unexposed median age 67 | Not reported | Adjusted for covariates | N/A | FGAs, SGAs | AP initiation during hospitalization | Unexposed | Discharge dg aspiration pneumonia | In persons 75 + years aOR 2.0, 95% CI 1.4–2.9 In persons aged 65–74 y aOR 1.4, 95% CI 0.8–2.4 |
Tolppanen et al. [16], 2016, Finland, nationwide registers | Cohort | Incident users with AD (n = 17,031) and without AD (n = 2714), non-users with AD (n = 43,553) and without AD (n = 57,870) | Mean age of cohorts 79.0–82.5 | Community-dwelling | 1:1 age-, sex- matched with non-AD cohort; propensity score | AD | FGAs, SGAs | AP initiation prior to pneumonia | Non-users | Hospitalization or death due to pneumonia | Exposed in AD aHR 2.01, 95% CI 1.90–2.13 non-AD cohort aHR 3.43, 95% CI 2.99–3.93 |
Huybrechts et al. [130]*, 2011, Canada, linked healthcare databases | Cohort | New FGA users (n = 1902), new SGA users (n = 1942) | ≥ 65 | Nursing homes | Propensity score | N/A | FGAs, SGAs | AP initiation after admission to nursing home | Non-users | Hospitalization for pneumonia within 180 days of drug initiation | RR 1.03, 95% CI 0.62–1.69 |
Hwang et al. [124], 2014, Canada, linked healthcare databases | Cohort | New SGA users (n = 97,777), non-users (n = 97,777) | ≥ 65 | Community-dwelling and LTCF | 1:1 propensity-score matched | N/A | SGAs | SGA initiation | Non-users | Hospitalization for pneumonia within 90 days of drug initiation | RR 1.50, 95% CI 1.39–1.62 |
Kim et al. [123], 2017, USA, Premier database | Cohort | FGA users (n = 832), SGA users (n = 832) after coronary artery bypass | Mean age 70 | Not reported | 1:1 propensity-score matched | Cardiac surgery patients | FGAs, SGAs | AP Initiation after cardiac surgery | FGA users | Discharge dg pneumonia and initiation of ≥ 2 antibiotics | RR 1.11, 95% CI 0.89–1.38 |
Jackson et al. [181]*, 2015, USA, Medicare | Cohort | New FGA users (n = 9060), new SGA users (n = 17,137) | ≥ 65 | Community-dwelling | Adjusted for covariates | N/A | FGAs, SGAs | AP initiation of prior to pneumonia | SGA users | Pneumonia (ICD codes) | aOR 1.57, 95% CI 1.05–2.34 |
Aparasu et al. [182]*, 2013, USA, Medicare and Medicaid | Cohort | FGA users (n = 3609), SGA users (n = 3609) | ≥ 65 | Nursing homes | 1:1 propensity-score matched | N/A | FGAs, SGAs | AP initiation | SGA users | Hospitalization for pneumonia within 6 months of drug treatment | HR 1.24, 95% CI 0.94–1.64 |
Huybrechts et al. [183]*, 2012, USA, Medicare and Medicaid | Cohort | New FGA users (n = 7463), new SGA users (n = 76,496) | ≥ 65 | Nursing homes | Propensity score | N/A | FGAs, SGAs | AP initiation prior to pneumonia diagnosis | SGA users | Hospitalization for pneumonia within 180-days of drug initiation | HR 1.28, 95% CI 0.87–1.88 |
Wang et al. [184]*, 2007, USA, Medicare | Cohort | New FGA users (n = 9142), new SGA users (n = 13,748) | ≥ 65 | Not reported | Adjusted for covariates | N/A | FGAs, SGAs | AP initiation | SGA users | Pneumonia dg (ICD codes) and initiation of antibiotic within 180-days of drug initiation | aHR 1.11, 95% CI 0.76–1.63 |
Mehta et al. [185]*, 2015, USA, administrative claims | Cohort | SGA users (n = 92,234) | ≥ 65 | Not reported | Propensity score | N/A | SGAs (quetiapine, risperidone, olanzapine, aripiprazole, and ziprasidone) | AP Initiation prior to pneumonia | Quetiapine | Fatal and nonfatal pneumonia (ICD codes) | Risperidone aHR 1.14, 95% CI 1.10–1.18, olanzapine aHR 1.10, 95% CI 1.04–1.17 |
Case–control studies | |||||||||||
Gau et al. [186]*+, 2010, USA, community hospital records | Case–control | Cases (n = 194) CAP, controls (n = 952) discharge dg different from pneumonia | ≥ 65 | Not reported | Adjusted for covariates | N/A | SGAs | SGA initiation | Non-users | Discharge dg of CAP and radiographic findings | aOR 2.26, 95% CI 1.23–4.15 |
Knol et al. [187]*+, 2008, The Netherlands, healthcare register data | Case–control | Cases (n = 543) pneumonia dg, controls (n = 2163) no hospitalization for pneumonia | ≥ 65 | Community-dwelling | Adjusted for covariates | N/A | FGAs, SGAs | AP initiation | Non-users | Hospitalization for pneumonia | Current AP users aOR 1.6, 95% CI 1.3–2.1 |
Hennessy et al. [125], 2007, UK, General Practice Research Database | Case–control | Cases (n = 12,044) pneumonia dg, Controls (n = 48,176) no hospitalization for pneumonia | ≥ 65 | Not reported | Matched 1:4 for General Practitioner practice; adjusted for covariates | N/A | FGAs, SGAs | AP initiation | Non-users | Hospitalization for pneumonia | aOR 1.82, 95% CI 1.64–2.02 |
Trifirò et al. [138]*+, 2010, The Netherlands, IPCI general practice | Case–control | Cases (n = 258) CAP dg, controls (n = 1686) no pneumonia dg | ≥ 65 | Community-dwelling | Adjusted for covariates | N/A | FGAs, SGAs | AP initiation | Past use of any AP | CAP dg with radiographic findings or confirmed by specialist | Current FGA users: aOR 1.76, 95% CI 1.22–2.53, current SGA users: aOR 2.61, 95% CI 1.48–4.61 |
Self-control studies | |||||||||||
Pratt et al. [188]*+, 2011, Australia, DVA health care claims | Self-controlled case series | FGA user (n = 807), SGA user (n = 1107) analyzed by AP exposure versus unexposed periods | ≥ 65 | Not reported | Within study design | N/A | FGAs, SGAs | AP initiation with pre and post initiation data | N/A | Hospitalization for pneumonia | AP use is associated with an increased risk of hospitalization for pneumonia |
Star et al. [189]*+, 2010, UK, IMS Health Disease Analyzer dataset | Self-controlled cohort analysis | Records reviewed 3 years before and after pneumonia dg | ≥ 65 | Not reported | Within study design | N/A | FGAs, SGAs | AP initiation | N/A | Pneumonia dg (ICD codes) | Increased number of pneumonia diagnoses was observed after initiation of SGAs |
5.2 Benzodiazepine and Benzodiazepine-Related Drugs
Study, year, country and data source | Study type | Participants (sample size) | Age (years) | Living arrangement | Confounders adjusted for | Population | Drugs investigated | Exposure definition | Comparison group | Outcome or case definition | Risk of pneumonia |
---|---|---|---|---|---|---|---|---|---|---|---|
Cohort studies | |||||||||||
Taipale et al. [190]*, 2017, Finland, nationwide registers | Cohort | New BZD users (n = 5232), new BZRD users (n = 3269), nonusers (n = 8501) | Mean age 80 | Community-dwelling | 1:1 propensity-score matched, adjusted for other psychotropic drugs | AD | BZDs, BZRDs | BZD or BZRD initiation after AD dg | Non-users | Hospitalization or death due to pneumonia | BZD: aHR 1.28, 95% CI 1.07–1.54 BZRD: aHR 1.10, 95% CI 0.84–1.44 |
Maeda et al. [191]*, 2016, Japan, late stage elderly health insurance | Cohort | BZD users (n = 13,015), with non-users (n = 13,015) | ≥65 | Not reported | Propensity-score matching | N/A | Triazolam | BZD initiation ≥ 180 days in a year | Non-users | Pneumonia dg (ICD codes) | aOR 1.40, 95% CI 1.30–1.51 |
Vozoris et al. [129], 2014, Canada, linked health care databases | Cohort | New BZD users (n = 48,915), non-users (n = 48,915) | >65 | Community-dwelling | 1:1 propensity-score matching | COPD | BZDs | BZD initiation | Non-users | Hospitalization for COPD exacerbation or pneumonia within 30-days of drug initiation | RR 1.09, 95% CI 1.00–1.20 |
Huybrechts et al. [130], 2011, Canada, linked health care databases | Cohort | New BZD users (n = 4887) and new SGA users (n = 1942) | ≥65 | Nursing homes | Propensity score | N/A | BZDs | BZD or SGA initiation after admission to nursing home | SGA users | Hospitalization for pneumonia within 180-days of drug initiation | RR 0.85, 95% CI 0.56–1.31 |
Case–control studies | |||||||||||
Wang et al. [128], 2017, Taiwan, National Health Insurance | Case–control | Cases (n = 4533) pneumonia dg, controls (n = 16,388) no pneumonia dg | Mean age 80 | Not reported | Adjusted for covariates | CKD | BZDs, BZRDs | BZD or BZRD initiation within 1 year prior to pneumonia dg | Non-users | Pneumonia dg with radiographic findings and initiation of antibiotic | Current BZD: aOR 1.31 95% CI 1.18–1.46 Current BZRD: aOR 1.07, 95% CI 0.80–1.44 |
Jung et al. [192]*, 2016, USA, Kaiser Permanent integrated health care system | Case–control | Cases (n = 51,029) pneumonia, controls (n = 188,391) no pneumonia | ≥65 | Community-dwelling | Adjusted for covariates | N/A | BZDs, BZRDs | BZD or BZRD initiation prior to pneumonia dg | Non-users | Pneumonia dg (ICD codes) | BZD: aOR 1.16, 95% CI 1.13–1.20 BZRD: aOR 1.14, 95% CI 1.08–1.20 |
Chung et al. [127], 2015, Taiwan, National Health Insurance | Case–control | Cases (n = 5171) pneumonia, controls (n = 11,342) with no adverse respiratory event | Mean age > 65 | Not reported | Adjusted for covariates | COPD | BZDs, BZRDs | BZD or BZRD initiation prior to pneumonia dg | Non-users | Pneumonia dg (ICD codes) | Current BZD: aOR 9.30, 95% CI 6.11–14.1 Current BZRD: aOR 11.3, 95% CI 8.16–15.6) |
Dublin et al. [74]*, 2011, USA, Group Health electronic health data | Case–control | Cases (n = 1039) CAP, controls (n = 2022) no pneumonia dg | ≥65 | Community-dwelling | Adjusted for covariates | N/A | BZDs | BZD initiation prior to pneumonia dg | Non-users | CAP dg (ICD codes) validated with radiographic finds or hospitalization records | aOR 1.08, 95% CI 0.80–1.47 |
Hennessy et al. [125], 2007, UK, General Practice Research Database | Case–control | Cases (n = 12,044) pneumonia dg, controls (n = 48,176) no hospitalization for pneumonia | ≥65 | Not reported | Matched 1:4 for general practitioner practice, adjusted for covariates | N/A | BZDs | BZD initiation | Non-users | Hospitalization for pneumonia | aOR 1.55, 95% CI 1.44–1.67 |
5.3 Antidepressants
Study, year, country and data source | Study type | Participants (sample size) | Age (years) | Accommodation | Confounders adjusted for | Population | Drugs investigated | Exposure definition | Comparison group | Outcome or case definition | Risk of pneumonia |
---|---|---|---|---|---|---|---|---|---|---|---|
Cohort studies | |||||||||||
Vozoris et al. [131], 2018, Canada, linked health care databases | Cohort | New users (n = 28,360), non-users (n = 28,360) | > 65 | Community-dwelling | Propensity-score matching | COPD | SSRIs, SNRIs | SSRI or SNRI initiation | Non-users | Hospitalization for COPD exacerbation or pneumonia | HR 1.15, 95% CI 1.03–1.25 |
Huybrechts et al. [130], 2011, Canada, linked health care databases | Cohort | New antidepressant users (n = 4887), new SGA users (n = 1942) | ≥ 65 | Nursing homes | Propensity score | N/A | Antidepressants | Antidepressant or SGA initiation after admission to nursing home | SGA users | Hospitalization for pneumonia within 180 days of drug initiation | RR 1.09, 95% CI 0.73–1.65 |
Case–control studies | |||||||||||
Hennessy et al. [125], 2007, UK, General Practice Research Database | Case–control | Cases (n = 12,044) pneumonia dg, controls (n = 48,176) no hospitalization for pneumonia | ≥ 65 | Not reported | Matched 1:4 for General Practitioner practice, adjusted covariates | N/A | Antidepressants | Antidepressant initiation | Non-users | Hospitalization for pneumonia | aOR 0.89, 95% CI 0.79–1.00 |
5.4 Antiepileptics
Study, year, country and data source | Study type | Participants (sample size) | Age (years) | Accommodation | Confounders adjusted for | Population | Drugs investigated | Exposure definition | Comparison group | Outcome or case definition | Risk of pneumonia |
---|---|---|---|---|---|---|---|---|---|---|---|
Taipale et al. [23] 2019, Finland, nationwide registers | Cohort | New AED users (n = 5769), non-users (n = 5769) | Mean age 80 | Community-dwelling | Adjusted for covariates | AD | AEDs | AED initiation after AD diagnosis | Non-users | Hospitalization or death due to pneumonia | aHR 1.92, 95% CI 1.63–2.26 |