Introduction
Methods
Data Source
Ethical Approval
Study Design
Cohort
SCCS
Participants, Exposure and Outcomes
Statistical Analyses (Cohort Study)
Propensity Score Fine-Stratification Weighting
Characteristic, no (%) | Crude | SMD | Weighted | SMD | ||
---|---|---|---|---|---|---|
Antipsychotic | Other psychotropica | Antipsychotic | Other psychotropica | |||
Age, mean(SD) | 25.7 (14) | 18.1 (12.2) | 0.582 | 25.7 (14) | 26.7 (17.5) | − 0.061 |
Gender | ||||||
Female | 906 (23.1) | 2391 (23.7) | − 0.014 | 906 (23.1) | 2353 (23.4) | − 0.006 |
Male | 3017 (76.9) | 7695 (76.3) | 0.014 | 3011 (76.9) | 7712 (76.6) | 0.006 |
Smoking and alcohol status | ||||||
Current smoker | 553 (14.1) | 957 (9.5) | 0.143 | 552 (14.1) | 1508 (15) | − 0.025 |
Ex-smoker | 265 (6.8) | 659 (6.5) | 0.009 | 265 (6.8) | 832 (8.3) | − 0.057 |
Problematic drinker | 203 (5.2) | 362 (3.6) | 0.078 | 203 (5.2) | 605 (6) | − 0.036 |
Comorbidities | ||||||
Neuropsychiatric comorbidities ( +) | 3346 (85.3) | 7554 (74.9) | 0.263 | 3340 (85.3) | 8635 (85.8) | − 0.015 |
Diabetes ( +) | 94 (2.4) | 114 (1.1) | 0.096 | 94 (2.4) | 276 (2.7) | − 0.022 |
Hypertension ( +) | 1079 (27.5) | 2860 (28.4) | − 0.019 | 1079 (27.5) | 3088 (30.7) | − 0.069 |
Stroke ( +) | 8 (0.2) | 10 (0.1) | 0.027 | 8 (0.2) | 21 (0.2) | 0 |
Medication use | ||||||
Current user of Antidiabetic medicationb | 30 (0.8) | 20 (0.2) | 0.082 | 30 (0.8) | 109 (1.1) | − 0.033 |
Ex-user of Antidiabetic medicationb | 9 (0.2) | 9 (0.1) | 0.035 | 9 (0.2) | 15 (0.2) | 0.018 |
Current user of Antihistamine | 804 (20.5) | 1761 (17.5) | 0.077 | 802 (20.5) | 2084 (20.7) | − 0.006 |
Ex-user of Antihistamine | 698 (17.8) | 2245 (22.3) | − 0.112 | 698 (17.8) | 1861 (18.5) | − 0.017 |
Current user of Tramadol | 27 (0.7) | 88 (0.9) | − 0.021 | 27 (0.7) | 82 (0.8) | − 0.014 |
Ex-user of Tramadol | 39 (1) | 115 (1.1) | − 0.014 | 39 (1) | 137 (1.4) | − 0.034 |
Current user of NSAID | 454 (11.6) | 1192 (11.8) | − 0.008 | 454 (11.6) | 1247 (12.4) | − 0.025 |
Ex- user of NSAID | 617 (15.7) | 2039 (20.2) | − 0.117 | 617 (15.8) | 1629 (16.2) | − 0.012 |
Current user of Cytostatic | 14 (0.4) | 19 (0.2) | 0.032 | 14 (0.4) | 34 (0.3) | 0.003 |
Ex-user of Cytostatic | 6 (0.2) | 18 (0.2) | − 0.006 | 6 (0.2) | 15 (0.2) | 0 |
Current user of Immunomodulator | 7 (0.2) | 22 (0.2) | − 0.009 | 7 (0.2) | 18 (0.2) | 0 |
Ex-user of Immunomodulators | 6 (0.2) | 11 (0.1) | 0.012 | 6 (0.2) | 38 (0.4) | − 0.043 |
ASM | ||||||
Current user of ASM | 400 (10.2) | 196 (1.9) | 0.351 | 394 (10.1) | 884 (8.8) | 0.044 |
Ex-user of ASM | 20 (0.5) | 18 (0.2) | 0.057 | 20 (0.5) | 44 (0.4) | 0.01 |
Current user of Benzodiazepine | 451 (11.5) | 272 (2.7) | 0.348 | 446 (11.4) | 1135 (11.3) | 0.003 |
Ex-user of Benzodiazepine | 49 (1.2) | 64 (0.6) | 0.064 | 49 (1.3) | 154 (1.5) | − 0.024 |
Sensitivity Analyses (Cohort Study)
Statistical Analyses (SCCS)
Sensitivity Analyses (SCCS)
Results
Cohort
Group | Patients (n) | Patient-years | Incident seizures (n) | Crude HR (95% CI) | Weighted HR (95% CI) |
---|---|---|---|---|---|
Primary analysis | |||||
Follow up end by earlier of: outcome date, medication has been switched or discontinued, death, patient left practice or study end date | |||||
Antipsychotic | 3923 | 11,914 | 65 | 1.59 (1.15–2.22) | 1.28 (0.74–2.19) |
Psychotropica | 10,086 | 22,577 | 82 | 1 | 1 |
Sensitivity analyses | |||||
1. Follow up end by earlier of: outcome date, death, patient left practice or study end date | |||||
Antipsychotic | 3923 | 15,238 | 77 | 1.70 (1.26–2.30) | 1.40 (0.85–2.30) |
Psychotropica | 10,086 | 30,306 | 94 | 1 | 1 |
2. Follow up end by earlier of: outcome date, death, patient left practice, study end date or 90 days after first continuous exposure | |||||
Antipsychotic | 3923 | 8988 | 52 | 1.80 (1.23–2.65) | 1.36 (0.72–2.57) |
Psychotropica | 10,086 | 15,601 | 55 | 1 | 1 |
SCCS
Characteristic | No. of patients (%) | Age at observation start, mean (SD), Y | Length of prescription, median (range) [IQR], d | Risk period (exposure) | Baseline period (no exposure) | ||
---|---|---|---|---|---|---|---|
Incident seizures, No | Total follow-up time, patient-years | Incident seizures, No | Total follow-up time, patient-years | ||||
1. Risk of incident seizure associated with antipsychotic exposure | |||||||
All | 149 (100) | 16.15 (14.03) | 49 (1–2553) [25–78] | 61 | 479.4 | 88 | 1049.9 |
Male | 119 (79.9) | 17.13 (14.59) | 50 (1–2553) [25–81] | 53 | 408.7 | 66 | 795 |
Female | 30 (20.1) | 12.23 (10.89) | 28 (1–471) [15–56] | 8 | 70.7 | 22 | 254.9 |
2. Risk of incident seizure associated with antipsychotic exposure (excluding patients died during study period) | |||||||
All | 147 (100) | 15.90 (13.71) | 60 | 469.2 | 87 | 1043.4 | |
Male | 117 (79.6) | 16.84 (14.23) | 50 (1–2553) [26–81] | 52 | 398.5 | 65 | 788.5 |
Female | 30 (20.4) | 12.32 (11.51) | 30 (1–1841) [27–65] | 8 | 70.7 | 22 | 254.9 |
3. Risk of otitis media associated with antipsychotic exposure (negative control) | |||||||
All | 334 (100) | 13.44(13.77) | 32 (1–3763) [16–71] | 73 | 972.4 | 261 | 2691.6 |
Male | 250 (74.8) | 12.32 (13.26) | 42 (1–3763) [21–74] | 54 | 737 | 196 | 2042.3 |
Female | 84 (25.1) | 16.78 (14.75) | 28 (2–3549) [14–60] | 19 | 235.4 | 65 | 649.3 |
Risk window | Incident seizures (n) | Patient-years | Adjusted IRR (95% CI) |
---|---|---|---|
1. Primary analysis, antipsychotic medication exposure and risk of incident seizure | |||
Baseline period | 88 | 1049.9 | – |
14 days pre antipsychotic exposure | 9 | 57.5 | 1.66 (0.74–3.71) |
First 30 days of antipsychotic exposure | 26 | 156.3 | 1.79 (0.97–3.30) |
Subsequent antipsychotic exposure | 26 | 265.6 | 1.02 (0.53–1.96) |
2. Sensitivity analysis, excluding patients died within observation period | |||
Baseline period | 87 | 1043.4 | – |
14 days pre antipsychotic exposure | 8 | 55.9 | 1.52 (0.65–3.58) |
First 30 days of antipsychotic exposure | 26 | 152.7 | 1.79 (0.96–3.35) |
Subsequent antipsychotic exposure | 26 | 260.6 | 1.08 (0.56–2.11) |
3. Negative outcome control, antipsychotic medication exposure and risk of incident otitis media | |||
Baseline period | 261 | 2691.6 | – |
14 days pre first antipsychotic exposure | 8 | 119.5 | 0.74 (0.32–1.73) |
First 30 days of antipsychotic exposure | 23 | 306.1 | 0.77 (0.42–1.39) |
Subsequent antipsychotic exposure | 42 | 546.8 | 0.75 (0.42–1.34) |