Table 1.
Summary of studies of exposure to antipsychotics (AP) and risk of pneumonia included in review
| 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 |
AD Alzheimer’s disease, aHR adjusted hazard ratio, aOR adjusted odds ratio, AP antipsychotics, CAP community-acquired pneumonia, CI confidence interval, dg diagnosis, FGA first-generation antipsychotic, HR hazard ratio, ICD International Statistical Classification of Diseases and Related Health Problems, LTFC long-term care facility, N/A not applicable, RR risk ratio, SGA second-generation antipsychotic
*Studies used in Dzahini et al. systematic review and meta-analysis [121]
+Studies used in Nosè et al. systematic review and meta-analysis [134]