Background
Methods
Results
Study | Population | Outcome | Propensity for bias/Study quality | Procedures to minimize bias | Follow-up | Outcome rate in reference group | Result |
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LEVEL I Evidence: Meta-Analyses
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Studies that compared atypical antipsychotic (ATYP) treatment to placebo (PLA)
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Katz [5] | 895 Institutionalised dementia patients (age>=55) | Death | Low/High | Yes | 12 weeks | 1.8% | HR(RISP v PLA); 1.26 95% CI; 0.53-2.99 |
Schneider [19] | 5,204 Dementia patients (age>55) | Death | Low/High | Yes | 6-26 weeks | 2.3% | OR(ATYP v PLA); 1.54 95% CI; 1.06-2.23 RD(ATYP - PLA); 0.01 95% CI; 0.004-0.02 |
2.8% | OR(RISP v PLA); 1.30 95%CI; 0.76-2.23 | ||||||
Haupt [20] | 1,721 Alzheimers Patients (mean age 82.3) | Death | Low/High | Yes | 4-12 weeks | 3.1% | RR(RISP v PLA); 1.21 95% CI; 0.71-2.06 |
LEVEL II Evidence: Randomised Controlled Trial
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Studies that compared atypical antipsychotic (ATYP) treatment to placebo (PLA)
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Ballard [21] | 165 Institutionalised dementia patients (mean age 85) | Death | Low/High | Yes | 12 months | 33% | HR(RISP v PLA); 0.58 95% CI; 0.36-0.92 |
Studies that compared conventional antipsychotic (C) treatment to placebo (PLA)
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DeDeyn [8] | 344 Dementia patients (mean age 81 placebo, 82 haloperidol) | Death | Low/High | Yes | 12 weeks | 3.8% | OR(HAL v PLA); 1.68 95% CI; 0.72-3.92 [19] |
LEVEL III Evidence: Observational Studies
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Studies that compared atypical antipsychotic (ATYP) treatment to non-use (NU)
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COHORT STUDIES
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Gill [22] | 9,100 matched pairs, Non-institutionalised dementia patients in a universal health fund in Ontario Canada (age>=65) | Death | Moderate/Moderate | Yes (Propensity score matching, sensitivity analysis) | 180 days | 8.0% | HR(ATYP v NU);1.32 95% CI; 1.12-1.54 RD(ATYP - NU); 1.1 per 100 95% CI; 0.1-2.1 |
Gill [22] | 4,036 matched pairs, Institutionalised dementia patients in a universal health fund in Ontario Canada (age>=65) | Death | Moderate/Moderate | Yes (Propensity score matching, sensitivity analysis) | 180 days | 15.1% | HR(ATYP v NU);1.23 95% CI; 1.05-1.45 RD(ATYP - NU); 1.5 per 100 95% CI; -0.5-3.4 |
CASE-CONTROL STUDIES
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Trifiro [23] | 398 cases, 4,023 controls, dementia patients, Integrated Primary Care Information Database (Netherlands)(age>85) | Death | Moderate/Low | Yes (matching on age and duration of dementia) | 9 years | NA | OR(ATYP v NU); 2.2 95% CI; 1.2-3.9 |
Raivio [24] | 254 institutionalized dementia patients (Finland) (age>70) | Death | Moderate/Low | Yes (covariate adjustment) | 2 years | 49.6% | HR(ATYP v NU);0.49 95% CI; 0.24-0.99 |
Studies that compared conventional antipsychotic (CONV) treatment to non-use (NU)
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COHORT STUDIES
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Ray [25] | 1,282,995 Non-institutionalised dementia, medicaid-enrolled patients (Tennessee) (age 15-84) | Sudden cardiac Death | Moderate/Moderate | Yes (covariate adjustment, sensitivity analysis) | 1 year | 11.3/10000 PY | Moderate Dose >100mg: RR(CONV v NU); 2.39 95% CI; 1.77-3.22 Low Dose <100mg: RR(CONV v NU); 1.3 95% CI; 0.98-1.72 |
Kales [26] | 10,615 Veterans enrolled in VA Serious Mental Illness Treatment Research and Evaluation Centre, Dementia Patients (US) (age>65) | Death | Moderate/Moderate | Yes (Propensity score adjustment, sensitivity analysis, subgroup analysis) | 1 year | 25.2% | RR(NU v CONV); 0.66 95% CI; 0.53-0.82 |
CASE-CONTROL STUDIES
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Trifiro [23] | 398 cases, 4,023 controls, dementia patients Integrated Primary Care Information Database (Netherlands) (age>85) | Death | Moderate/Low | Yes (matching on age and duration of dementia) | 9 years | NA | OR(CONV v NU); 1.8 95% CI; 1.4-2.3 |
Raivio [24] | 254 institutionalized dementia patients (Finland) (age>70) | Death | Moderate/Low | Yes (covariate adjustment) | 2 years | 49.6% | HR(CONV v NU); 0.68 95% CI; 0.46-1.03 |
Studies that compared conventional antipsychotic (CONV) and atypical antipsychotic (ATYP) treatment
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COHORT STUDIES
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Gill [22] | 9,100 matched pairs, Non-institutionalised dementia patients (age>=65) | Death | Moderate/Moderate | Yes (Propensity score matching, sensitivity analysis) | 180 days | 10.7% | HR(CONV v ATYP); 1.23 95% CI; 1.00-1.50 RD(CONV - ATYP); 2.6 per 100 95% CI; 0.5-4.5 |
Gill [22] | 4,036 matched pairs, Institutionalised dementia patients (age>=65) | Death | Moderate/Moderate | Yes (Propensity score matching, sensitivity analysis) | 180 days | 17.8% | HR(CONV v ATYP); 1.27 95% CI; 1.09-1.48 RD(CONV - ATYP); 2.2 per 100 95% CI; 0.0-4.4 |
Hollis [27] | 16,634 Australian Department of Veterans Affairs Veterans/spouses (Australia) (age>65) | Death | Moderate/Moderate | Yes (covariate adjustment) | 2 years | 246 per 1000 | RR (HALO v OLA); 2.26 95% CI; 2.08-2.47 RR (CHL v OLA); 1.39 95% CI; 1.15-1.67 |
Hollis [27] | 6,602 Institutionalised Australian Department of Veterans Affairs Veterans/spouses (Australia) (age>65) | Death | Moderate/Moderate | Yes (covariate adjustment) | 2 years | 291 per 1000 | RR (HALO v OLA); 1.67 95% CI; 1.50-1.84 RR (CHL v OLA); 1.75 95% CI; 1.31-2.34 |
Kales [26] | 10,615 Veterans enrolled in VA Serious Mental Illness Treatment Research and Evaluation Centre, Dementia Patients (US) (age>65) | Death | Moderate/Moderate | Yes (Covariate and propensity score adjustment, sensitivity analysis, subgroup analysis) | 1 year | 25.2% | Covariate adjusted RR(ATYP v CONV); 0.93 95% CI; 0.75-1.16 |
Schneeweiss [28] | 37,241 British Columbia Residents (Canada) (age>=65) | Death | Moderate/Moderate | Yes (Covariate and propensity score adjustment, instrumental variable analysis) | 180 days | 9.6% | Covariate adjusted HR(CONV v ATYP); 1.32 95% CI; 1.23-1.42 PS adjusted HR(CONV v ATYP); 1.39 95% CI; 1.30-1.49 IV RD(CONV – ATYP); 4.2 per 100, 95% CI; 1.2-7.3 |
Wang [29] | 22,890 Drug Insurance Beneficiaries (Pennsylvania US) (age>=65) | Death | Moderate/Moderate | Yes (Covariate and propensity score adjustment, instrumental variable analysis) | 180 days | 14.6% | Covariate adjusted HR(CONV v ATYP); 1.37 95% CI; 1.27-1.49 Propensity score adjusted adjusted HR(CONV v ATYP); 1.37 95% CI; 1.27-1.49 IV RD(CONV - ATYP); 7.3 per 100 95% CI; 2.0-12.6 |
Liperoti [30] | 9,729 Institutionalised dementia patients (age >=65) | Death | Moderate/Moderate | Yes (covariate adjustment, sensitivity analysis, subgroup analysis) | 180 days | 40.0 per 100 person-years | HR(CONV v ATYP); 1.26 95% CI; 1.13-1.42 HR (HALO v RISP); 1.31 95% CI; 1.13–1.53 HR(Phenothiazines V RISP); 1.17 95% CI; 1.00–1.38 HR(Other Conventional v RISP); 1.32 95% CI; 0.99–1.80 |
Pratt [31] | 7,311 Institutionalised Australian Department of Veterans Affairs Veterans/spouses (Australia) (Age >65) | Death | Moderate/Moderate | Yes (Propensity score adjustment, instrumental variable analysis) | 1 year | 37.4% | Covariate adjusted RD(CONV v ATYP); 8.5 95% CI; 6.2-10.7 Propensity score adjusted RD(CONV v ATYP); 9.1 95% CI; 6.9-11.4 IV RD(CONV - ATYP); 10.1 per 100 95% CI; 6.6-13.7 |
CASE-CONTROL STUDIES
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Trifiro [23] | 398 cases, 4,023 controls, dementia patients Integrated Primary Care Information Database (Netherlands) (age>85) | Death | Moderate/Low | Yes (matching on age and duration of dementia) | Up to 9 years | NA | OR(ATYP v CONV); 1.3 95% CI; 0.7-2.4 |
Study | Population | Outcome | Propensity for bias / Study quality | Procedures to minimize bias | Follow-up | Outcome Rate in reference group | Result |
---|---|---|---|---|---|---|---|
LEVEL I Evidence: Meta-Analyses
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Studies that compared atypical antipsychotic (ATYP) treatment to placebo (PLA)
| |||||||
Ballard [1] | 1954 dementia patients (age> 60) | CV Events | Low/High | Yes | 10-13 weeks | 1.0% | RR (RISP v PLA); 3.64 95% CI; 1.72-7.69 |
Schneider [6] | 5,110 Dementia patients (mean age 81.2) | CV Events | Low/High | Yes | 6-26 weeks | 0.9% 1.0% | OR (ATYP v PLA); 2.13 95% CI; 1.20-3.75 OR(RISP v PLA); 3.43 95%CI; 1.60-7.32 |
DeDeyn [4] | 1,155 Institutionalised patients (age>=55) | CV Events | Low/High | Yes | 12 weeks | 1.6% | Rate in Risperidone group 3.9% RR not reported |
Hermann [32] | 1,721 Dementia patients (age>=55) | CV Events | Low/High | Yes | 12 weeks | 1.1% | RR (RISP v PLA); 3.2 95% CI; 1.4-7.2 |
Katz [5] | 895 Institutionalised dementia patients (age>=55) | CV Events | Low/High | Yes | 12 weeks | 0.8% | Rate in Risperidone group 1.6% RR not reported |
DeDeyn [4] | 1,155 Institutionalised patients (age>=55) | Serious CV Event requiring hosp. | Low/High | Yes | 12 weeks | 0.7% | Rate in Risperidone group 1.6% RR not reported |
Hermann [32] | 1,721 Dementia patients (age>=55) | Serious CV Event requiring hosp. | Low/High | Yes | 12 weeks | 0.6% | RR (RISP v PLA); 2.3 95% CI; 0.5-10.7 |
LEVEL III Evidence: Observational Studies
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Studies that compared atypical antipsychotic (ATYP) treatment to non-use (NU)
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COHORT STUDIES
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Sacchett [33] | 74,162 All patients, General Practitioner Health Search database (Italy) (age>=65) | Diagnosis of stroke (GPs’ medical records) ICD9: 434.9, 438.0, 342 | Moderate/Moderate | Yes (covariate adjustment, subgroup analysis) | 3.5 months | 12 per 1000py | RR (ATYP v UNEX); 2.46 95% CI; 1.07-5.65 |
Barnett [34] | 14,029 Dementia patients, Veterans Affairs Clients (US) (age>=65) | Hospital Admission for CV event ICD9 435, 437, 430, 432, 433, 434 | Moderate/Moderate | Yes (covariate adjustment, sensitivity analysis) | 18 months | 3.2% | HR (ATYP v NU); 1.20 95% CI; 0.83-1.74 |
CASE-CONTROL STUDIES
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Kolanowski [35] | 959 Dementia patients, health care insured on Southeast US (age>70) | Diagnosis of Stroke | Moderate/ Low | Yes (unmatchedcovariate adjustment) | 45 days | NA | OR (ATYP v NU); 0.98 95% CI; 0.64-1.52 |
Liperoti [36] | 1130 cases, 3658 controls, institutionalised dementia patients in six states in the US (Ohio, Maine, Illinois, Mississippi, South Dakota, New York) (age>85) | Hospital Admission for CV event ICD9 433.0-434.9 (Ischaemic stroke) 435-435.9 (TIA) | Moderate/ Low | Yes (matching on admitted to same facility for septicemia, UTI) | NR | NA | OR (RISP v NU); 0.87 95% CI; 0.67-1.12 OR (OLA v NU); 1.32 95% CI; 0.83-2.11 OR (Other ATYP v NU); 1.57 95% CI; 0.65-3.82 |
SELF-CONTROLLED CASE-SERIES STUDIES
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Douglas [37] | 6790 All patients with incident diagnosis of stroke General Practice Research Database (UK) (no age restriction) | Diagnosis of stroke (GPs’ medical records, excluding TIA) | Moderate/Moderate | Yes (within patient design) | NR | NA | IRR (ATYP v NU); 2.32 95% CI; 1.73-3.10 |
Pratt [38] | 10638 Australian Department of Veterans Affairs Veterans/spouses with hospitalization for stroke (Australia) (age>=65) | Hospitalis-ation for stroke ICD-10: I60-I64 | Moderate/Moderate | Yes (within patient design) | 4 years | NA | IRR (ATYP v NU); 0.9 95% CI; 0.7-1.0 |
Studies that compared conventional antipsychotic (CONV) treatment to non-use (NU)
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COHORT STUDIES
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Sacchetti [33] | 74,162 All patients, General Practitioner Health Search database (Italy) (age>=65) | Diagnosis of stroke (GPs’ medical records) ICD9: 434.9, 438.0, 342 | Moderate/Moderate | Yes (covariate adjustment, subgroup analysis) | 3.5 months | 12 per 1000py | RR (BUTY v UNEX); 3.55 95% CI; 1.56-8.07 RR (PHENO v UNEX); 5.79 95% CI; 3.07-10.9 |
Barnett [34] | 14,029 Dementia patients, Veterans Affairs Clients (US) (age>=65) | Hospital Admission for CV event ICD9 435, 437, 430, 432, 433, 434 | Moderate/Moderate | Yes (covariate adjustment, sensitivity analysis) | 18 months | 3.2% | HR (CONV v NU); 1.20 95% CI; 0.48-3.47 |
CASE-CONTROL STUDIES
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Kolanowski [35] | 959 Dementia patients, health care insured on Southeast US (age>70) | Diagnosis of Stroke | Moderate/ Low | Yes (Unmatched, covariate adjustment) | 45 days | NA | OR (CONV v NU); 1.18 95% CI; 0.63-2.24 |
Liperoti [36] | 1130 cases, 3658 controls, institutionalised dementia patients in six states in the US (Ohio, Maine, Illinois, Mississippi, South Dakota, New York) (age>85) | Hospital Admission for CV event ICD9 433.0-434.9 (Ischaemic stroke) 435-435.9 (TIA) | Moderate /Low | Yes (matched; on admitted to same facility for septicemia, UTI) | NR | NA | OR (CONV v NU); 1.24 95% CI; 0.95-1.63 |
SELF-CONTROLLED CASE-SERIES STUDIES
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Douglas [37] | 6790 All patients with incident diagnosis of stroke General Practice Research Database (UK) (no age restriction) | Diagnosis of stroke (GPs’ medical records, excluding TIA) | Moderate/Moderate | Yes (within patient design) | NR | NA | IRR (CONV v NU); 1.60 95% CI; 1.55-1.84 |
Pratt [38] | 10638 Australian Department of Veterans Affairs Veterans/spouses with hospitalization for stroke (Australia) (age>=65) | Hospitalis-ation for stroke ICD-10: I60-I64 | Moderate/Moderate | Yes (within patient design) | 4 years | NA | IRR (CONV v NU); 1.0 95% CI; 0.8-1.2 |
Studies that compared all antipsychotics (ANTIP) with no treatment (NU)
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COHORT STUDIES
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Percudani [39] | 1645978 All patients in Lombardy Italy with CV related Outcome in 2002 (age>=65) | Hospital Admission for CV related outcome ICD9 430--438 | Moderate/Low | Yes (unmatched covariate adjustment) | 2 years | 2.15 % | OR (ANTIP v NU); 1.24 95% CI; 1.16-1.32 |
Sacchetti [40] | 134488 All patients, General Practitioner Health Search database (Italy) (age>50) | Diagnosis of stroke (GPs’ medical records) ICD9: 434.9, 438.0, 342 | Moderate/Moderate | Yes (covariate adjustment) | 6 months | 3.6 per 1000py | 1 month: RR (ANTIP v NU); 12.4 95% CI; 8.4-18.1 |
Kleijer [41] | 2448 Patients in community pharmacy practice, PHARMO Database (Netherlands) (age>50) | Hospital Admission for stroke (inc TIA) ICD9 430-436 | Moderate/Low | Yes (matched: age/sex) | 1 year | NA | Current use: OR (ANTIP v NU); 1.6 95% CI 1.3-2.0 0-7 days: OR (ANTIP v NU); 9.9 (5.7-17.2) 8-14 days :OR (ANTIP v NU);2.6 (1.3-5.3) 15-30 days: OR (ANTIP v NU); 2.1 (1.0-4.5) 31-90 days: OR (ANTIP v NU); 1.5 (1.0-2.2) >90 days: OR (ANTIP v NU); 1.0 (0.7-1.3) |
Studies that compared conventional antipsychotic (C) and atypical antipsychotic (A) treatment
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COHORT STUDIES
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Hermann [42] | 11400 All patients, population based cohort (Canada) (age>65) | Hospital Admission for stroke ICD9 430-436 | Moderate/Moderate | Yes (covariate adjustment) | 5 years | 5.7 per 1000py | RR (RISP v CONV); 1.4 95% CI; 0.7-2.8 RR (OLA v CONV); 1.1 95% CI; 0.5-2.3 |
Gill [43] | 32710 Dementia patients, administrative health care database (Canada) (age>=65) | Hospital Admission for ischaemic stroke ICD9 431, 434,436 | Moderate/Moderate | Yes (covariate adjustment, subgroup analysis) | 5 years | 6.3 % | HR(ATYP v CONV); 1.01 95% CI; 0.81-1.26 |
Finkel [44] | 18477 Dementia patients, Medicaid database (US) (age>60) | Hospital Admission for stroke ICD( 430-432, 434-436, 437.1, 437.9 | Moderate/Moderate | Yes (covariate adjustment) | 3 months | 0.87 % | OR (OLA v RISP); 1.1 95% CI; 0.6-1.7 OR (QUE v RISP); 0.78 95% CI; 0.2-1.9 OR (HAL v RISP); 1.9 95% CI; 1.0-3.6 |
Percudani [39] | 1645978 All patients with CV related outcome in 2002 (Italy) (age>=65) | Hospital Admission for CV related outcome ICD9 430--438 | Moderate/Low | Yes (unmatched covariate adjustment) | 2 years | 2.37 % | OR (ATYP v CONV); 1.42 95% CI; 1.24-1.64 |
Wang [45] | 22890 Patients in Pharmacy Assistance Contract for Elderly Program (US) (age>=65) | Hospital Admission for stroke, cerebral hemorrhagic and ischemic events | Moderate/Moderate | Yes (Propensity score adjustment, instrumental variable analysis) | 180 days | Not Reported | 30 days: HR (CONV v ATYP); 1.08 95% CI; 0.99-1.18 60 days: HR (CONV v ATYP) 1.10 95% CI; 1.02-1.19 180 days: HR (CONV v ATYP) 1.09 95% CI; 1.02-1.16 IV analyses not reported |
Sacchetti [33] | 74,162 All patients, General Practitioner Health Search database (Italy) (age>=65) | Diagnosis of stroke (GPs’ medical records) ICD9: 434.9, 438.0, 342 | Moderate/Moderate | Yes (covariate adjustment, subgroup analysis) | 3.5 months | 47.4 per 1000py | RR (BUTY v ATYP); 1.44 95% CI; 0.55-3.76 RR (PHENO v ATYP); 2.34 95% CI; 1.01-5.41 |
Study | Population | Outcome | Propensity for bias/Study quality | Procedures to minimize bias | Follow-up | Outcome Rate in reference group | Result |
---|---|---|---|---|---|---|---|
LEVEL III Evidence: Observational Studies
| |||||||
Studies that compared atypical antipsychotic (ATYP) treatment to non-use (NU)
| |||||||
COHORT STUDIES
| |||||||
Normand [46] | 1286395 All patients (Canada) (age>65) | Hip fracture | Moderate/Low | Yes (covariate adjustment) | NR | NR | OR (ATYP v NU); 2.2 95% CI; 2.1-2.4 |
CASE-CONTROL STUDIES
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Liperoti [47] | 1787 cases, 5606 controls Institutionalised patients (US) (age>=65) | Hospitalisation for hip fracture ICD9 820-821 | Moderate/Moderate | Yes (matched on; admitted to same facility for septicemia, GI, MI) | NR | NA | OR (ATYP v NU); 1.37 95% CI; 1.11-1.69 OR (RISP v NU); 1.42 95% CI; 1.12-1.80 OR (OLA v NU); 1.34 95% CI; 0.87-2.07 OR (OTHERATYP v NU); 1.03 95% CI; 0.47-2.28 |
Kolanowski [35] | 959 Dementia patients, health care insured on Southeast US (age>70) | Diagnosis of hip Fracture | Moderate/Low | Yes (unmatched covariate adjustment) | 45 days | NA | OR (ATYP v NU); 1.47 95% CI; 0.82-2.65 |
Pouwels [48] | 6763 cases, 26341 controls All patients, PHARMO Database (Netherlands) (age>18) | Hospitalis-ation for Hip fracture | Moderate/Low | Yes (Matched on; year of birth, sex, geographic region) | 12 years | NA | OR (ATYP v NU); 0.83 95% CI; 0.42-1.65 |
Jalbert [49] | 764 cases, 3582 controls Long stay Medicaid-eligible resident living in nursing homes with at least 20 beds (age>65) | Hospitalis-ation for Hip fracture ICD9 820 | Moderate/Low | Yes (Matched; admitted to same facility, covariate adjustment) | 2 years | NA | New use: OR (ATYP v NU); 1.36 95% CI; 0.95-1.94 Prevalent use: OR (ATYP v NU); 1.33 95% CI; 1.08-1.63 |
SELF-CONTROLLED CASE SERIES STUDIES
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Pratt [50] | 8285, Australian Department of Veterans Affairs Veterans/spouses with hospitalization for hip fracture (Australia) (age>=65) | Hospitalis-ation for Hip fracture ICD10 S720, S721 | Moderate/Moderate | Yes (within patient design) | 4 years | NA | 1 week: IRR (ATYP V UEXP); 2.17 95% CI; 1.54-3.06 2-8 weeks: IRR (ATYP V UEXP); 1.27 95% CI; 1.04-1.55 9-12 weeks: IRR (ATYP V UEXP); 1.23 95% CI; 0.92-1.63 >12 weeks: IRR (ATYP V UEXP); 1.43 95% CI; 1.23-1.66 |
Studies that compared conventional antipsychotic (CONV) treatment to non-use (NU)
| |||||||
CASE-CONTROL STUDIES
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Liperoti [47] | 1787 cases, 5606 controls Institutionalised patients (US) (age>=65) | Hospitalis-ation for hip fracture | Moderate | Yes (covariate adjustment and matched; on admitted to same facility for septicemia,GI,MI) | NR | NA | OR (CONV v NU); 1.35 95% CI; 1.06-1.71 OR (HALO v NU); 1.53 95% CI; 1.18-2.26 OR (OTHERCONV v NU); 1.09 95% CI; 0.78-1.52 |
Kolanowski [35] | 959 Dementia patients, health care insured on Southeast US (age>70) | Diagnosis of hip Fracture | Moderate | Yes (covariate adjustment) | 45 days | NA | OR (CONV v NU); 2.33 95% CI; 1.08-5.03 |
Pouwels [48] | 6763 cases, 26341 controls All patients, PHARMO Database (Netherlands) (age>18) | Hospitalis-ation for Hip fracture | Moderate | Yes (Matched; year of birth, sex, geographic region) | 12 years | NA | OR (CONV v NU); 1.76 95% CI; 1.48-2.08 |
Jalbert [49] | 764 cases, 3582 controls Long stay Medicaid-eligible resident living in nursing homes with at least 20 beds (age>65) | Hospitalis-ation for Hip fracture | Moderate | Yes (Matched; admitted to same facility) | 2 years | NA | Prevalent use: OR (CONV v NU); 1.28 95% CI; 0.7-2.34 |
SELF-CONTROLLED CASE SERIES STUDIES
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Pratt et al. [50] | 8285, Australian Department of Veterans Affairs Veterans/spouses with hospitalization for hip fracture (Australia) (age>=65) | Hospitalis-ation for Hip fracture ICD10 S720, S721 | Moderate | Yes (within patient design) | 4 years | NA | 1 week: IRR (CONV V UEXP); 1.04 95% CI; 0.40-2.70 2-8 weeks: IRR (CONV V UEXP); 2.23 95% CI; 1.65-3.02 9-12 weeks: IRR (CONV V UEXP); 1.79 95% CI; 1.12-2.84 >12 weeks: IRR (CONV V UEXP); 2.19 95% CI; 1.62-2.95 |
Studies that compared all antipsychotics with non-use (NU)
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CASE-CONTROL STUDIES
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Wang [51] | 1222 cases, 4888 controls Elderly patients enrolled in Medicare as well as in the New Jersey Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs (age>=65) | Hospitalis-ation for hip fracture | Moderate/Moderate | Yes (matched on; year birth and gender, covariate adjustment) | NR | NA | OR (ATYP v NU); 1.60 95% CI NR |
Studies that compared conventional antipsychotic (CONV) and atypical antipsychotic (ATYP) treatment
| |||||||
COHORT STUDIES
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Normand [46] | 1286395 All patients, in Ontario (Canada) (age>65) | Hip fracture | Moderate/Low | Yes (covariate adjustment) | NR | NR | OR (ATYP v CONV); 0.5 95% CI; 0.4-0.5 |
Study | Population | Outcome | Propensity for bias/Study quality | Procedures to minimize bias | Follow-up | Outcome Rate in reference group | Result |
---|---|---|---|---|---|---|---|
LEVEL III Evidence: Observational Studies
| |||||||
Studies that compared atypical antipsychotic (ATYP) treatment to non-use (NU)
| |||||||
CASE-CONTROL STUDIES
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Knol [52] | 543 cases, 2163 controls All patients; no prior pneumonia, PHARMO Database (Netherlands) (age>=65) | hospital diagnosis of pneumonia ICD9 480-486, 507 | Moderate/Low | Yes (unmatched covariate adjustment) | 6 months | NR | OR (ATYP v NU); 3.1 95% CI; 1.9-5.1 |
Trifiro [53] | 258 cases, 1686 controls Elderly patients from Dutch General Practice database (IPCI) patients (age>=65) | Fatal or non-fatal diagnosis of pneumonia | Moderate/Low | Yes (matched; `age/sex) | 11 years | NA | Current use: OR (ATYP v PU); 2.6 95% CI; 1.5-4.6 Recent use: OR (ATYP v PU); 1.4 95% CI; 0.5-4.1 |
Gau [54] | 194 cases, 952 controls Patients admitted to community hospital, Ontario (Canada) (age>=65) | Hospitalisation for pneumonia | Moderate/Low | Yes (matched; hospitalization for another diagnosis) | 12 months | NA | OR (ATYP v NU); 2.3 95% CI; 1.2-4.2 |
SELF-CONTROLLED CASE SERIES STUDIES
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Pratt [50] | 13932, Australian Department of Veterans Affairs Veterans/spouses with hospitalization for pneumonia (Australia) (age>=65) | Hospitalisation for pneumonia ICD10 J12–J18 | Moderate/Moderate | Yes (within patient design) | 4 years | NA | 1 week:IRR (ATYP V UEXP); 1.73 95% CI; 1.31-2.29 2-8 weeks: IRR (ATYP V UEXP); 1.70 95% CI; 1.48-1.95 9-12 weeks: IRR (ATYP V UEXP); 1.67 95% CI; 1.37-2.04 >12 weeks: IRR (ATYP V UEXP); 1.70 95% CI; 1.51-1.93 |
Studies that compared conventional antipsychotic (CONV) treatment to non-use (NU)
| |||||||
CASE-CONTROL STUDIES
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Knol [52] | 543 cases, 2163 controls All patients; no prior pneumonia, PHARMO Database (Netherlands) (age>=65) | hospital diagnosis of pneumonia ICD9 480-486, 507 | Moderate/Low | Yes (matched) | 6 months | NA | OR (CONV v NU); 1.5 95% CI; 1.2-1.9 |
Trifiro[53] | 258 cases, 1686 controls Elderly patients from Dutch General Practice database (IPCI) patients (age>=65) | Fatal or non-fatal diagnosis of pneumonia | Moderate/Low | Yes (matched) | 11 years | NA | Current use: OR (CONV v PU); 1.8 95% CI; 1.2-2.5 Recent use: OR (CONV v PU); 1.3 95% CI; 0.8-2.0 |
SELF-CONTROLLED CASE SERIES STUDIES
| |||||||
Pratt [50] | 13932, Australian Department of Veterans Affairs Veterans/spouses with hospitalization for pneumonia (Australia) (age>=65) | Hospitalisation for pneumonia ICD10 J12–J18 | Moderate/Moderate | Yes (within patient design) | 4 years | NA | 1 week: IRR (CONV V UEXP); 1.51 95% CI; 1.07, 2.14 2-8 weeks: IRR (CONV V UEXP); 1.62 95% CI; 1.37, 1.92 9-12 weeks: IRR (CONV V UEXP); 1.69 95% CI; 1.32, 2.16 >12 weeks: IRR (CONV V UEXP); 1.63 95% CI; 1.36, 1.96 |
Studies that compared antipsychotic (ANTIP) treatment to non-use (NU)
| |||||||
CASE-CONTROL STUDIES
| |||||||
Knol [52] | 543 cases, 2163 controls All patients; no prior pneumonia, PHARMO Database (Netherlands) (age>=65) | hospital diagnosis of pneumonia ICD9 480-486, 507 | Moderate/Low | Yes (matched) | 6 months | NA | 0-8 days: OR (ANTIP v NU); 4.4 95% CI; 2.9-7.2 8-14 days: OR (ANTIP v NU); 2.3 95% CI; 1.1-4.9 15-30 days: OR (ANTIP v NU); 1.9 95% CI; 1.0-3.1 31-90 days: OR (ANTIP v NU); 2.0 95% CI; 1.1-3.0 >90 days: OR (ANTIP v NU); 1.1 95% CI; 0.9-0.6 |
Wada [55] | 121, Alzheimers patients in psychiatric hospital patients; (mean age 78.2) | pneumonia | High/Low | No (unmatched) | Not reported | Not reported | OR (ANTIP v NU); 3.13 95% CI; 1.46-6.69 |
Studies that compared conventional antipsychotic (CONV) and atypical antipsychotic (ATYP) treatment
| |||||||
COHORT STUDIES
| |||||||
Wang [45] | 22890 Patients in Pharmacy Assistance Contract for Elderly Program (age>=65) | Hospital Admission for pneumonia plus prescription for an antibiotic medication | Moderate/Moderate | Yes (Propensity score adjustment, instrumental variable analysis) | 180 days | NR | 30 days: HR (CONV v ATYP); 1.11 95% CI; 0.76-1.63 60 days: HR (CONV v ATYP); 1.03 95% CI; 0.76-1.38 180 days: HR (CONV v ATYP); 0.84 95% CI; 0.66-1.05 IV analyses not reported |
Trifiro [53] | 258 cases, 1686 controls Elderly patients from Dutch General Practice database (IPCI) patients (age>=65) | Fatal or non-fatal diagnosis of pneumonia | Moderate/Low | Yes (matched) | 11 years | NA | Current use: OR (ATYP V CONV); 1.48 95% CI; 0.84-2.60 Current use: OR (ATY/PHENO v BUTY); 1.86 95% CI; 1.09-3.17 |
Risk of death associated with antipsychotic medicines
Meta-analysis and RCT evidence: studies that compared antipsychotic treatment to placebo
Observational evidence: studies that compared antipsychotic treatment to non-use
Observational evidence: studies that compared conventional and atypical antipsychotic treatment
Risk of cerebrovascular events associated with antipsychotic medicines
Meta-analysis and RCT evidence: studies that compared antipsychotic treatment to placebo
Observational evidence: studies that compared antipsychotic treatment to non-use
Observational evidence: studies that compared conventional and atypical antipsychotic treatment
Risk of hip fracture associated with antipsychotic medicines
Meta-analysis and RCT evidence: studies that compared antipsychotic treatment to placebo
Observational evidence: studies that compared antipsychotic treatment to non-use
Observational evidence: studies that compared atypical and conventional antipsychotic treatment
Risk of pneumonia associated with antipsychotic medicines
Meta-analysis and RCT evidence: studies that compared antipsychotic treatment to placebo
Observational evidence: studies that compared antipsychotic treatment to non-use
Discussion
Conclusions
Study
|
Study Design
|
Follow-up
|
Risperidone n/N (%)
|
Placebo n/N (%)
|
RD
|
NNT
| |
---|---|---|---|---|---|---|---|
Clinical End Point
| |||||||
>50% Improvement in Behave-AD
1
total score
| |||||||
Katz [62] | Double-blind placebo controlled RCT (n=625) | 12 weeks | (45%) | (33%) | 12% | 8 | |
Schneider [6] | Meta Analysis of 3 studies (n=1001) | 12 weeks | 266/574 (46%) | 139/427 (33%) | 14% | 7.4 | |
>30% Improvement in Behave-AD
1
total score
| |||||||
DeDeyn [8] | Double-blind placebo controlled RCT (n=344) | 12 weeks | (72%) | (61%) | 11% | 9 | |
CGI-C
2
(much/very much improved)
| |||||||
Brodaty [61] | Double-blind placebo controlled RCT (n=93) | 12 weeks | 27/46 (59%) | 12/47 (26%) | 33% | 3.3 | |
Schneider [6] | Meta Analysis of 2 studies (n=717) | 8-12 weeks | 227/351 (65%) | 175/366 (48%) | 17% | 6 | |
Katz [5] | Meta Analysis of 4 studies (n=889) | End point | (28%) | (17%) | 11% | 9 | |
Sultzer [63] | Double-blind placebo controlled RCT (n=421) | 12 weeks | (61%) | (40%) | 21% | 5 |