Table 1 Studies on the risk of death associated with antipsychotic medicines
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 | |||||||
Studies that compared atypical antipsychotic (ATYP) treatment to placebo (PLA) | |||||||
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 | |||||||
Studies that compared atypical antipsychotic (ATYP) treatment to placebo (PLA) | |||||||
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) | |||||||
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 | |||||||
Studies that compared atypical antipsychotic (ATYP) treatment to non-use (NU) | |||||||
COHORT STUDIES | |||||||
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 | |||||||
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) | |||||||
COHORT STUDIES | |||||||
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 | |||||||
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 | |||||||
COHORT STUDIES | |||||||
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 | |||||||
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 |