Table 2.
Number, incidence rates per 10,000 person-years, and 95% confidence intervals for each drug–medical event combination (phase 2a) for the whole study period 1997–2016, where the number of events was greater than or equal to five
| Medical event | Total | Citalopram | Escitalopram | Sertraline | Venlafaxine | Duloxetine | Paroxetine | Fluoxetine |
|---|---|---|---|---|---|---|---|---|
| Blood and lymphatic system disorders | ||||||||
| Aplastic anemiaa | 45; 1.0 (0.7–1.3) | 33; 1.3 (0.9–1.9) | 5; 1.1 (0.3–2.5) | NA | NA | NA | NA | NA |
| ITPa | 14; 0.3 (0.2–0.5) | 7; 0.3 (0.1–0.6) | 5; 1.1 (0.3–2.5) | NA | NA | NA | NA | NA |
| Thrombocytopenia | 88; 1.9 (1.5–2.4) | 56; 2.3 (1.7–3.0) | 12; 2.5 (1.3–4.4) | 9; 1.1 (0.5–2.1) | 5; 2.0 (0.7–4.7) | NA | NA | NA |
| Agranulocytosisa | 33; 0.7 (0.5–1.0) | 16; 0.6 (0.4–1.1) | 6; 1.3 (0.5–2.8) | NA | NA | NA | NA | NA |
| Immune system disorders | ||||||||
| Anaphylaxisa | 47; 1.0 (0.7–1.4) | 25; 1.0 (0.7–1.5) | 6; 1.3 (0.5–2.8) | NA | NA | NA | NA | NA |
| Psychiatric disorders | ||||||||
| Mania | 123; 2.7 (2.2–3.2) | 64; 2.6 (2.0–3.3) | 10; 2.1 (1.0–3.9) | 21; 2.6 (1.6–3.9) | 7; 2.8 (1.1–5.8) | NA | 12; 4.1 (2.1–7.2) | NA |
| Hallucinations | 31; 0.7 (0.5–1.0) | 19; 0.8 (0.5–1.2) | NA | 5; 0.6 (0.2–1.4) | NA | NA | NA | NA |
| Delusionsa | 457; 10.0 (9.1–10.9) | 216; 8.8 (7.7–10.1) | 53; 11.3 (8.4–14.7) | 78; 9.6 (7.6–12.0) | 27; 10.9 (7.2–15.9) | 8; 12.7 (5.5–25.0) | 38; 13.1 (9.3–18.0) | 37; 14.4 (10.2–19.9) |
| Suicide | 841; 18.2 (17.0–19.5) | 440; 17.9 (16.2–19.6) | 93; 19.7 (15.9–24.1) | 145; 17.8 (15.0–21.0) | 66; 26.5 (20.5–33.7) | 13; 20.6 (10.9–35.1) | 46; 15.8 (11.5–21.0) | 38; 14.8 (10.5–20.3) |
| Self-harm | 320; 7.0 (6.2–7.8) | 155; 6.3 (5.4–7.4) | 37; 7.9 (5.5–10.8) | 49; 6.1 (4.5–8.0) | 31; 12.5 (8.5–17.8) | NA | NA | 24; 9.3 (6.0–13.9) |
| Nervous system disorders | ||||||||
| Epilepsy and seizures | 1278; 28.1 (26.6–29.7) | 883; 36.4 (34.0–38.8) | 116; 24.8 (20.5–29.8) | 153; 19.0 (16.1–22.3) | 39; 15.8 (11.3–21.6) | 9; 14.4 (6.6–27.2) | 41; 14.2 (10.2–19.3) | 37; 14.5 (10.2–20.0) |
| Hemorrhagic stroke | 663; 14.5 (13.4–15.6) | 410; 16.8 (15.2–18.5) | 88; 18.8 (15.1–23.1) | 88; 10.9 (8.7–13.4) | 29; 11.7 (7.8–16.8) | 7; 11.1 (4.5–22.9) | 20; 6.9 (4.2–10.6) | 21; 8.2 (5.1–12.5) |
| Ischemic stroke | 3340; 77.0 (74.4–79.6) | 2189; 96.7 (92.7–108.5) | 334; 74.8 (67.0–83.3) | 442; 56.2 (51.1–61.7) | 118; 48.5 (40.2–58.1) | 30; 48.8 (32.9–69.6) | 104; 36.3 (29.7–44.0) | 123; 49.0 (40.7–58.4) |
| Polyneuropathy | 79; 1.7 (1.4–2.1) | 39; 1.6 (1.1–2.2) | 9; 1.9 (0.9–3.6) | 13; 1.6 (0.9–2.7) | NA | NA | 9; 3.1 (1.4–5.9) | 5; 2.0 (0.6–4.6) |
| Cardiac disorders | ||||||||
| Arrhythmia | 2111; 48.1 (46.1–50.2) | 1317; 56.7 (53.7–59.9) | 226; 50.5 (44.2–57.6) | 279; 35.6 (31.6–40.1) | 103; 42.6 (34.8–51.7) | 29; 47.9 (32.1–68.7) | 81; 28.5 (22.6–35.4) | 76; 30.2 (23.8–37.8) |
| Ventricular arrhythmia | 193; 4.2 (3.6–4.8) | 114; 4.6 (3.8–5.6) | 23; 4.9 (3.1–7.3) | 30; 3.7 (2.5–5.3) | 7; 2.8 (1.1–5.8) | NA | NA | 10; 3.9 (1.9–7.2) |
| Ventricular fibrillationa | 46; 1.0 (0.7–1.3) | 30; 1.2 (0.8–1.7) | 5; 1.1 (0.3–2.5) | 6; 0.7 (0.3–1.6) | NA | NA | NA | NA |
| Myocardial infarction | 1679; 37.1 (35.4–39.0) | 1109; 46.1 (43.4–48.9) | 174; 37.6 (32.2–43.6) | 216; 27.0 (23.5–30.8) | 56; 22.8 (17.2–29.6) | 16; 25.7 (14.7–41.7) | 62; 21.5 (16.5–27.6) | 46; 18.1 (13.3–24.2) |
| Cardiomyopathies | 141; 3.1 (2.6–3.6) | 82; 3.3 (2.7–4.1) | 23; 4.9 (3.1–7.3) | 14; 1.7 (0.9–2.9) | 7; 2.8 (1.1–5.8) | NA | 11; 3.8 (1.9–6.8) | NA |
| Cardiac arresta | 247; 5.4 (4.7–6.1) | 159; 6.5 (5.5–7.5) | 30; 6.4 (4.3–9.1) | 38; 4.7 (3.3–6.4) | 7; 2.8 (1.1–5.8) | NA | NA | 5; 1.9 (0.6–4.5) |
| Heart failure | 1840; 40.9 (39.1–42.8) | 1215; 50.9 (48.1–53.9) | 185; 40.2 (34.6–46.4) | 256; 32.0 (28.2–36.2) | 55; 22.3 (16.8–29.1) | 11; 17.7 (8.8–31.6) | 54; 18.7 (14.0–24.4) | 64; 25.2 (19.4–32.2) |
| Vascular disorders | ||||||||
| Pulmonary hypertensiona | 26; 0.6 (0.4–0.8) | 14; 0.6 (0.3–1.0) | NA | 7; 0.9 (0.3–1.8) | NA | NA | NA | NA |
| Respiratory, thoracic, and mediastinal disorders | ||||||||
| Pulmonary fibrosisa | 93; 2.0 (1.6–2.5) | 57; 2.3 (1.8–3.0) | 10; 2.1 (1.0–3.9) | 11; 1.4 (0.7–2.4) | 8; 3.2 (1.4–6.3) | NA | NA | NA |
| Gastrointestinal disorders | ||||||||
| Intestinal perforationa | 34; 0.7 (0.5–1.0) | 24; 1.0 (0.6–1.4) | 6; 1.3 (0.5–2.8) | NA | NA | NA | NA | NA |
| Pancreatitis acutea | 315; 6.9 (6.1–7.7) | 175; 7.1 (6.1–8.3) | 40; 8.5 (6.1–11.6) | 45; 5.6 (4.0–7.4) | 15; 6.0 (3.4–10.0) | 6; 9.5 (3.5–20.7) | 19; 6.5 (3.9–10.2) | 15; 5.9 (3.3–9.7) |
| Pancreatitis acute, sensitivity | 300; 6.5 (5.8–7.3) | 164; 6.7 (5.7–7.8) | 39; 8.3 (5.9–11.3) | 43; 5.3 (3.8–7.1) | 14; 5.6 (3.1–9.5) | 6; 9.5 (3.5–20.7) | 19; 6.5 (3.9–10.2) | 15; 5.9 (3.3–9.7) |
| Autoimmune pancreatitisa | 72; 1.6 (1.2–2.0) | 39; 1.6 (1.1–2.2) | 11; 2.3 (1.2–4.2) | 11; 1.4 (0.7–2.4) | NA | NA | NA | NA |
| Pancreatitisa, all | 352; 7.7 (6.9–8.5) | 198; 8.1 (7.0–9.3) | 45; 9.6 (7.0–12.8) | 49; 6.0 (4.5–8.0) | 17; 6.9 (4.0–11.0) | 8; 12.7 (5.5–25.0) | 20; 6.9 (4.2–10.6) | 15; 5.9 (3.3–9.7) |
| Hepatobiliary disorders | ||||||||
| Hepatotoxicity | 364; 7.9 (7.1–8.8) | 205; 8.3 (7.2–9.6) | 46; 9.8 (7.1–13.0) | 57; 7.0 (5.3–9.1) | 18; 7.3 (4.3–11.5) | 9; 14.3 (6.5–27.1) | 16; 5.5 (3.1–8.9) | 13; 5.1 (2.7–8.7) |
| Toxic liver diseasea | 105; 2.3 (1.9–2.8) | 54; 2.2 (1.6–2.9) | 8; 1.7 (0.7–3.3) | 22; 2.7 (1.7–4.1) | 9; 3.6 (1.7–6.9) | NA | NA | 5; 1.9 (0.6–4.5) |
| Hepatic necrosisa | 23; 0.5 (0.3–0.7) | 10; 0.4 (0.2–0.7) | NA | 8; 1.0 (0.4–1.9) | NA | NA | NA | NA |
| Hepatic failurea | 211; 4.6 (4.0–5.2) | 134; 5.4 (4.6–6.4) | 32; 6.8 (4.6–9.6) | 21; 2.6 (1.6–4.0) | NA | NA | 9; 3.1 (1.4–5.9) | 6; 2.3 (0.9–5.1) |
| Acute hepatic failurea | 63; 1.4 (1.1–1.7) | 38; 1.5 (1.1–2.1) | 11; 2.3 (1.2–4.2) | 6; 0.7 (0.3–1.6) | NA | NA | NA | NA |
| Skin and subcutaneous tissue disorders | ||||||||
| Angio-neurotic edemaa | 67; 1.5 (1.1–1.8) | 38; 1.5 (1.1–2.1) | 8; 1.7 (0.7–3.3) | 11; 1.4 (0.7–2.4) | NA | NA | NA | NA |
| Musculoskeletal and connective tissue disorders | ||||||||
| Fractures | 7553; 186 (181–190) | 5012; 233 (227–240) | 748; 179 (166–192) | 939; 129 (121–138) | 265; 119 (105–134) | 53; 93.9 (70.4–123) | 261; 98.7 (87.1–111) | 275; 119 (105–134) |
| Renal and urinary disorders | ||||||||
| Acute kidney injurya | 337; 7.3 (6.6–8.1) | 219; 8.9 (7.8–10.2) | 49; 10.4 (7.7–13.7) | 38; 4.7 (3.3–6.4) | 9; 3.6 (1.7–6.9) | NA | 10; 3.4 (1.6–6.3) | NA |
| Renal failurea | 813; 17.8 (16.6–19.0) | 542; 22.2 (20.4–24.2) | 108; 23.1 (18.9–27.9) | 92; 11.4 (9.2–13.9) | 20; 8.1 (4.9–12.5) | 7; 11.2 (4.5–23.0) | 17; 5.8 (3.4–9.3) | 27; 10.5 (6.9–15.3) |
| Hyponatremia | 1257; 27.4 (25.9–29.0) | 791; 32.3 (30.1–34.6) | 143; 30.4 (25.6–35.8) | 182; 22.5 (19.3–26.0) | 51; 20.6 (15.3–27.0) | 20; 31.8 (19.4–49.1) | 44; 15.1 (11.0–20.3) | 26; 10.1 (6.6–14.9) |
Data are presented as N; incidence rate (95% confidence interval). Number of events less than five was marked with NA due to confidentiality requirements from Statistics Denmark
ITP immune thrombocytopenic purpura, NA not available
aEvents from the European Medicines Agency's Designated Medical Event list