Table 2.
Results of Individual Studies
| Study | Outcome | Number of events (data used in analysis)/no outcome | Risk estimate (95% CI) | Variables accounted for |
|---|---|---|---|---|
| Berdot et al. 2009 | Falls | 2673/3670 | *RR 1.19 (1.06–1.34) | *Unadjusted RR produced using no fall against ≥1 fall as RR presented in study combined no fall 1 fall against ≥2 falls. |
| Campbell et al. 2010 | Dementia | 339/1313 | OR 1.43 (0.98–2.07) | Adjusting for age at baseline, gender, education, and baseline CSI-D score. |
| Carriere et al. 2009 | Dementia | 221 (177)/6691 | HR 1.65 (1.00–2.73) | Adjusted for centre, age, sex, education, BMI, alcohol, tobacco and caffeine intake, mobility, hypercholesterolemia, ApoE ε4, diabetes mellitus, asthma, depression, ischemic diseases, Parkinson’s disease and hypertension. |
| Coupland et al. 2011 | Falls | 11 251/42 912 | Amitriptyline HR 1.32 (1.22–1.42) | Adjusted for gender, age (5-year bands), year, depression severity, depression before age 65 years, smoking status, Townsend deprivation score, CHD, diabetes, hypertension, stroke, cancer, dementia, epilepsy/seizures, Parkinson’s disease, hypothyroidism, obsessive–compulsive disorder, statins, NSAIDs, antipsychotics, lithium, aspirin, antihypertensives, anticonvulsants and hypnotics/anxiolytics. |
| Mirtazapine HR 1.19 (1.05–1.36) | ||||
| Paroxetine HR 1.45 (1.31–1.59) | ||||
| Trazodone HR 1.55 (1.29–1.87) | ||||
| All-cause mortality | 17 834/49 495 | Amitriptyline HR 1.10 (1.03–1.18) | Adjusted for gender, age (5-year bands), year, depression severity, depression before age 65 years, smoking status, Townsend deprivation score, CHD, diabetes, hypertension, stroke, cancer, dementia, epilepsy/seizures, Parkinson’s disease, hypothyroidism, OCD, statins, NSAIDs, antipsychotics, lithium, aspirin, antihypertensives, anticonvulsants and hypnotics/anxiolytics. | |
| Mirtazapine HR 1.76 (1.62–1.91) | ||||
| Paroxetine HR 1.24 (1.14–1.35) | ||||
| Trazodone HR 1.82 (1.59–2.08) | ||||
| Fox et al. 2011 | All-cause mortality | 1223/11 027 | ACB OR 1.26 (1.20–1.32) | Adjusting for age, sex, baseline MMSE score, education, social class, number of non-AC medications, and number of health conditions. |
| Hien et al. 2005 | Falls | 226 (75)/1779 | Olanzapine HR 1.74 (1.04–2.90) | Adjusted for other psychotropics in the model, age, sex, type of residential care facility, length of stay (log), RCS score, Implicit Illness, Severity Scale score, MMSE score, Parkinson’s disease, previous falls, and static balance score. One hundred sixty subjects were missing from analysis because of missing data on one or more variables. |
| Risperidone HR 1.32 (0.57–3.06) | ||||
| Hoffmann et al. 2003 | Falls | 47/447 | No. (%) | No adjustments |
| Olanzapine 23 (11.3%) | ||||
| Risperidone 18 (9.2%) | ||||
| Placebo 6 (6.4%) | ||||
| Olanzapine *OR 1.86 (0.73–4.74) | *Unadjusted OR produced using raw numbers. | |||
| Risperidone *OR 1.48 (0.57–3.87) | ||||
| Lackner et al. 2008 | Falls | 3/47 | Oxybutynin *OR 0.44 (0.04–5.19) | *Unadjusted OR produced using raw numbers. |
| Lowry et al. 2011 | All-cause mortality | 36/326 | ARS score HR 1.04 (0.67–1.62) | Adjusted for age, sex, institution, dementia, CCI, number of non-AC drugs, hospital site, Barthel Index category (<50 vs. 50+). |
| Lowry et al. 2012 | All-cause mortality | 36/326 | DBI (AC) HR 1.10 (0.44–2.74) | Adjusted for age, sex, institution, dementia, CCI, number of non-AC drugs, hospital site, Barthel Index category (<50 vs. 50+). |
| Luukkanen et al. 2011 | All-cause mortality | 198/227 | HR 1.12 (0.75–1.68) | Adjusted for age, CCI, male gender. |
| Mangoni et al. 2013 | All-cause mortality | 9/62 (3 months) | 3 months | *Adjusted for age, sex, CCI, preadmission cognitive impairment. |
| 18/53 (1 year) | *ARS score HR 1.6 (1.2–2.2) | No adjustments for rest of estimates. | ||
| ADS HR 1.3 (0.9–1.9) | ||||
| ABS HR 1.1 (0.7–1.8) | ||||
| DBI (AC) HR 4.5 (1.2–16.7) | ||||
| 1 year | ||||
| ARS scale HR 1.4 (1.1–1.8) | ||||
| ADS HR 1.2 (0.9–1.6) | ||||
| ACB HR 1.1 (0.7–1.8) | ||||
| DBI (AC) HR 3.2 (1.1–9.4) | ||||
| Marras et al. 2012 | All-cause mortality | 5391 (368)/25 937 | Quetiapine OR 1.8 (1.1–3.0) | Adjusted for CCI score, dementia, and changes in residence (community to long term care) between cohort entry and index date |
| Panula et al. 2009 | All-cause mortality | 229/232 | Males: | Males: Adjusted for age, cardiovascular disease, chronic lung disease. |
| 30 days: HR 2.19 (0.76–6.29) | ||||
| 3 months: HR 2.52 (1.05–6.03) | ||||
| 6 months: HR 2.22 (0.99–5.01) | *Females: no association between anticholinergics and mortality | |||
| 1 year: HR 1.99 (1.09–3.63) | ||||
| Females: *no data provided | ||||
| Thapa et al. 1998 | Falls | 3524 (2649)/N/A | Amitriptyline Rate ratio 1.9 (1.7–2.1) | Adjusted for age, sex, race, time since admission to the facility and since the index date, BMI, ambulatory status, no. of activities of daily living in which the resident was totally dependent on care providers, incontinence, cognitive impairment, use of physical restraints, previous falls, and use of anticonvulsants, antiparkinsonian drugs, benzodiazepines, antipsychotics, and other sedatives. |
| Imipramine Rate ratio 2.2 (1.8–2.6) | ||||
| Nortriptyline Rate ratio 2.0 (1.8–2.3) | ||||
| Paroxetine Rate ratio 1.7 (1.5–1.9) | ||||
| Trazodone Rate ratio 1.2 (1.0–1.4) | ||||
| Trifiro et al. 2007 | All-cause mortality | 407 (232)/4023 | Clozapine OR 1.8 (0.3–11.2) | Adjusted for gender and factors changing the risk estimate for antipsychotic users by more than 5% (Heart failure, COPD, Parkinson(ism), home-bound lifestyle, benzodiazepines and antibiotics). |
| Olanzapine OR 6.7 (1.4–32.1) | ||||
| Quetiapine OR no data | ||||
| Risperidone OR 1.7 (0.9–3.4) | ||||
| Uusvaara et al. 2011 | All-cause mortality | 71/329 | HR 1.57 (0.78–3.15) | Adjusted for age, sex, CCI. |
| Whalley et al. 2012 | Dementia | 45/226 | HR 0.67 (0.40–1.15) | Adjusted for age, female gender, IQ at age 11, education, history of dementia in a parent or sibling, personal history of treated heart disease, personal history of treated hypertension; exposed to AC drugs (mild-moderate-strong), APOE ε4. |
Abbreviations: AC: anticholinergic; ACB: anticholinergic cognitive burden scale; ADS: anticholinergic drug scale; APOE: apolipoprotein E; ARS: anticholinergic risk scale; BMI: body mass index; CCI: Charlson comorbidity index; CI: confidence interval; CHD: coronary heart disease; COPD: chronic obstructive pulmonary disease; CSI-D: Communtiy Screening Interview for Dementia score; DBI: drug burden index; HR: hazard ratio; IQ: intelligence quotient; MMSE: Mini-Mental State Examination; NSAIDs: non-steroidal anti-inflammatory drugs; OCD: obsessive–compulsive disorder; OR: odds ratio; RCS: Residential Classification Scale; RR: relative risk.