Introduction
Method
Data Source
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National Health Service (NHS) Administrative Register, which is a register of all individuals registered with a Welsh general practitioner (GP) or who have ever had contact with the NHS;
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General Practice Primary Care attendance and clinical information database for all general practice interactions including symptoms, investigations, diagnoses including co-morbidities, prescribed medication and referrals to secondary and tertiary care. The GPD database covered approximately 40% of the population of Wales at the time of the study;
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Cause of death (Office of National Statistics Public Health Mortality files);
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Patient Episode Dataset for Wales (PEDW), which includes demographic and clinical data on all inpatient and day-case admissions in NHS Wales hospitals and all Welsh residents treated in other UK countries;
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Outpatient Dataset, a minimum dataset listing all outpatient appointments, including mental health services in NHS Wales hospitals.
Study Cohort
Exposure to Antipsychotic and Other Psychotropic Medications
Clinical Characteristics, Co-morbidity and Outcomes
Statistical Analysis
Secondary Analyses
Additional Sensitivity Analyses
Compliance with Ethics Guidelines
Results
Cohort Characteristics
General characteristics of study cohort | Exposed to antipsychotic medication (n = 3735) | Not exposed to antipsychotic medication (n = 5939) | % Difference (95% CI) |
---|---|---|---|
Female | 66.2% (2474) | 67.8% (4025) | 1.5* (0–3.4) |
Mean age at diagnosis of dementia (years) | 82.4 (6.8) | 82.5 (6.8) | 0.1 (−0.1 to 0.4) |
History of | |||
Epilepsy | 2.7% (99) | 2.3% (138) | 0.3 (−0.3 to 1.0) |
Parkinsonism | 4.0% (149) | 3.7% (222) | 0.25 (−0.5 to 1.1) |
Atrial fibrillation | 14.6% (546) | 15.4% (914) | 0.7 (−2.2 to 0.7) |
Venous thromboembolism | 5.8% (217) | 5.5% (329) | 0.27 (−0.6 to 1.2) |
Diabetes | 13.7% (511) | 15.8% (941) | 2.2* (0.7–3.6) |
Ischaemic heart disease | 23.9% (893) | 23.2% (1377) | 0.7 (−1.0 to 2.5) |
Cerebrovascular disease | 22.3% (832) | 22.5% (1338) | 0.25 (−2.0 to 1.5) |
Hip fracture | 6.5% (243) | 6.1% (364) | 0.4 (−0.6 to 1.4) |
Antipsychotic Exposure, Mortality and Other Main Outcomes
Time to | Exposed to antipsychotic medication | Not exposed to antipsychotic medication | Adjusted HR Model 1 (95% CI)a
| Adjusted HR Model 2 (95% CI)b
| ||||
---|---|---|---|---|---|---|---|---|
Events | Follow-up years | Rate per 100 person-years (95% CI) | Events | Follow-up years | Rate per 100 person-years (95% CI) | |||
All older people with all-cause dementia (n = 9674) | 2342 | 100.9 | 23.2 (22.2–24.2) | 2777 | 121.9 | 22.8 (22.0–23.6) | 1.0 (0.96–1.09) | 1.06 (0.99–1.13) |
Older people with Alzheimer’s disease (n = 6996) | 1689 | 74.0 | 22.8 (22.2–23.9) | 2006 | 90.2 | 22.2 (21.2–23.2) | 1.02 (0.96–1.09) | 1.06 (0.99–1.14) |
Older people with all-cause dementia known to primary care only (n = 5089) | 1122 | 37.7 | 29.8 (28.1–31.6) | 1834 | 61.0 | 30.0 (28.7–31.5) | 1.0 (0.91–1.10) | 1.03 (0.96–1.10) |
Adverse event | Exposed to antipsychotic | Not exposed to antipsychotic | Hazard ratio | PERR (95% CI) |
---|---|---|---|---|
Acute cardiac event
| ||||
All-cause dementia | ||||
Before | ||||
N per 1000 | 5.9 (22/3721) | 7.1 (42/5908) | 0.83 | |
95% CI | 3.9–9.0 | 5.2–9.6 | ||
After | ||||
N per 1000 | 12.4 (46/3720) | 15.1 (89/5908) | 0.82 | 0.98 (1.0–1.0) |
95% CI | 9.2–16.6 | 12.2–18.6 | ||
Alzheimer’s | ||||
Before | ||||
N per 1000 | 5.2 (14/2690) | 9.6 (41/4270) | 0.54 | |
95% CI | 3.1–8.8 | 7.0–13.0 | ||
After | ||||
N per 1000 | 11.1 (30/2680) | 12.4 (53/4260) | 0.89 | 1.65* (1.59–1.86) |
95% CI | 7.8–16.0 | 9.5–16.2 | ||
Known to primary care only | ||||
Before | ||||
N per 1000 | 5.5 (9/1642) | 8.5 (29/3419) | 0.64 | |
95% CI | 2.9–10.5 | 5.8–12.2 | ||
After | ||||
N per 1000 | 14.1 (23/1634) | 12.9 (44/3408) | 1.08 | 1.68* (1.05–1.78) |
5% CI | 9.3-21.1 | 9.6-17.3 | ||
Venous thromboembolism
| ||||
All-cause dementia | ||||
Before | ||||
N per 1000 | 6.4 (24/3717) | 6.7 (40/5909) | 0.96 | |
95% CI | 4.3–9.6 | 5.0–9.2 | ||
After | ||||
N per 1000 | 13.0 (48/3705) | 6.9 (41/5914) | 1.88 | 1.95* (1.83–2.0) |
95% CI | 9.8–17.2 | 5.1–9.4 | ||
Alzheimer’s | ||||
Before | ||||
N per 1000 | 7.0 (19/2684) | 6.5 (28/4276) | 1.0 | |
95% CI | 4.5-11.0 | 5.0-9.2 | ||
After | ||||
N per 1000 | 14.2 (38/2674) | 7.7 (33/4274) | 1.8 | 1.80* (1.67–1.89) |
95% CI | 10.3-19.5 | 5.4-10.8 | ||
Known to primary care only | ||||
Before | ||||
N per 1000 | 6.7 (11/1639) | 9.6 (33/3416) | 0.7 | |
95% CI | 0.3–12.1 | 5.0–9.2 | ||
After | ||||
N per 1000 | 14.1 (23/1632) | 7.6 (26/3422) | 1.85 | 2.66* (2.41–2.78) |
95% CI | 9.3–21.2 | 5.2–11.1 | ||
Stroke
| ||||
All-cause dementia | ||||
Before | ||||
N per 1000 | 35.0 (128/3652) | 37.8 (219/5789) | 0.92 | |
95% CI | 29.4–41.6 | 33.1–43.1 | ||
After | ||||
N per 1000 | 65.8 (236/3587) | 50.8 (292/5749) | 1.3 | 1.41* (1.40–1.46) |
95% CI | 57.9–74.7 | 45.2–57.0 | ||
Alzheimer’s | ||||
Before | ||||
N per 1000 | 25.6 (68/2653) | 34.0 (143/4207) | 0.75 | |
95% CI | 20.2–32.4 | 28.8–40.0 | ||
After | ||||
N per 1000 | 61.1 (159/2601) | 39.6 (166/4190) | 1.54 | 2.06* (1.97–2.13) |
95% CI | 52.3–71.4 | 34.0–46.1 | ||
Known to primary care only | ||||
Before | ||||
N per 1000 | 41.9 (67/1599) | 50.2 (167/3327) | 0.83 | |
95% CI | 32.9–53.2 | 43.1–58.4 | ||
After | ||||
N per 1000 | 70.2 (111/1581) | 48.6 (162/3330) | 1.44 | 1.73* (1.66–1.75) |
95% CI | 58.2–84.5 | 41.7–56.7 | ||
Hip fracture
| ||||
All-cause dementia | ||||
Before | ||||
N per 1000 | 24.4 (90/3679) | 24.5 (143/5842) | 1.0 | |
95% CI | 19.9-30.1 | 20.8-28.8 | ||
After | ||||
N per 1000 | 55 (200/3617) | 34.2 (199/5817) | 1.61 | 1.62* (1.59–1.65) |
95% CI | 47.9–63.2 | 29.8-39.3 | ||
Alzheimer’s | ||||
Before | ||||
N per 1000 | 27.1 (72/2653) | 25.3 (107/4226) | 1.07 | |
95% CI | 21.5–34.2 | 20.9–30.6 | ||
After | ||||
N per 1000 | 59.0 (154/2608) | 33.4 (141/4213) | 1.76 | 1.65* (1.61–1.71) |
95% CI | 50.4–69.1 | 28.3–39.4 | ||
Known to primary care only | ||||
Before | ||||
N per 1000 | 25.2 (41/1623) | 22.4 (76/3390) | 1.13 | |
95% CI | 18.5–34.3 | 17.9–28.1 | ||
After | ||||
N per 1000 | 57.1 (91/1593) | 32.3 (109/3369) | 1.76 | 1.57* (1.52–1.65) |
95% CI | 46.5–70.1 | 26.8–39.0 |