Background
Methods
Cohort
Registers
Exposure
Outcome
Study setting
Covariates
Antidepressant nonuser (n = 21,820) | Antidepressant user (n = 10,910) | Unadjusted OR (95% CI) | Propensity score adjusted OR (95% CI) | |
---|---|---|---|---|
Female gender (matching criteria) | 69.0% (15,064) | 69.0% (7532) | 1.00 (0.95–1.05) | 0.94 (0.90–1.00) |
Aged ≥80 years (matching criteria) | 51.6% (11,261) | 51.4% (5613) | 0.99 (0.95–1.04) | 0.94 (0.90–1.00) |
Socioeconomic position | ||||
High | 34.7% (7578) | 33.5% (3659) | Reference | Reference |
Medium | 57.8% (12,618) | 59.2% (6463) | 1.06 (1.01–1.12) | 1.04 (0.98–1.09) |
Low | 6.3% (1380) | 6.0% (655) | 0.98 (0.90–1.09) | 0.92 (0.83–1.01) |
Unknown | 1.1% (244) | 1.2% (133) | 1.13 (0.91–1.40) | 1.06 (0.85–1.33) |
Comorbidities | ||||
Cardiovascular disease | 50.6% (11,043) | 50.7% (5533) | 1.00 (0.96–1.05) | 1.00 (0.95–1.05) |
Chronic heart failure | 28.1% (6124) | 29.8% (3215) | 1.09 (1.03–1.14) | 1.00 (0.95–1.06) |
Cardiac arrhythmia | 6.6% (1441) | 7.4% (807) | 1.13 (1.03–1.24) | 1.00 (0.91–1.10) |
Hypertension | 30.0% (6543) | 31.6% (3445) | 1.08 (1.03–1.13) | 1.00 (0.95–1.05) |
Epilepsy | 2.1% (451) | 1.8% (198) | 0.87 (0.74–1.04) | 0.99 (0.83–1.17) |
Asthma/COPD | 8.4% (1837) | 8.5% (925) | 1.01 (0.93–1.10) | 1.00 (0.92–1.09) |
Any chronic pulmonary disease | 10.4% (2258) | 11.1% (1209) | 1.08 (1.00–1.16) | 1.00 (0.93–1.08) |
Pulmonary circulation disorders | 0.1% (19) | 0.1% (11) | 1.16 (0.55–2.44) | 1.01 (0.48–2.15) |
Diabetes | 14.1% (3066) | 12.8% (1395) | 0.90 (0.84–0.96) | 0.99 (0.93–1.06) |
Complicated diabetes | 16.1% (3506) | 14.9% (1625) | 0.91 (0.86–0.98) | 0.99 (0.93–1.06) |
Schizophrenia | 1.3% (282) | 1.1% (121) | 0.86 (0.69–1.06) | 0.97 (0.78–1.21) |
Bipolar disorder/depression | 1.8% (388) | 2.7% (291) | 1.51 (1.30–1.77) | 1.00 (0.85–1.17) |
Psychosis | 3.7% (806) | 5.7% (624) | 1.58 (1.42–1.76) | 1.00 (0.90–1.12) |
Metastatic cancer | 0.2% (41) | 0.2% (18) | 0.88 (0.51–1.53) | 0.99 (0.56–1.74) |
Any tumor | 12.2% (2666) | 13.0% (1420) | 1.08 (1.00–1.15) | 1.00 (0.93–1.08) |
Renal failure | 1.3% (273) | 1.0% (109) | 0.80 (0.64–1.00) | 0.97 (0.77–1.22) |
Hemiplegia | 0.5% (99) | 0.5% (59) | 1.19 (0.86–1.65) | 1.01 (0.72–1.40) |
Coagulopathy | 0.6% (135) | 0.7% (78) | 1.16 (0.87–1.53) | 1.01 (0.75–1.34) |
Liver disease | 1.1% (231) | 1.0% (110) | 0.95 (0.76–1.20) | 0.99 (0.79–1.26) |
Peripheral vascular disorder | 4.4% (958) | 5.0% (550) | 1.16 (1.04–1.29) | 1.00 (0.90–1.12) |
Anemia | 6.8% (1485) | 6.4% (693) | 0.93 (0.85–1.02) | 0.99 (0.90–1.09) |
Fluid and electrolyte disorders | 2.9% (633) | 3.4% (367) | 1.17 (1.02–1.33) | 1.00 (0.87–1.14) |
Alcohol abuse | 1.1% (239) | 1.5% (162) | 1.36 (1.11–1.66) | 1.01 (0.81–1.23) |
Substance abuse | 1.6% (343) | 2.0% (218) | 1.28 (1.08–1.52) | 1.00 (0.84–1.19) |
Previous hospital-treated fracture | 19.1% (4165) | 21.3% (2328) | 1.15 (1.09–1.22) | 1.00 (0.95–1.07) |
Hip fracture | 5.3% (1153) | 6.2% (673) | 1.18 (1.07–1.30) | 1.00 (0.91–1.11) |
Stroke | 8.8% (1928) | 10.1% (1097) | 1.15 (1.07–1.25) | 1.01 (0.93–1.09) |
Drug use | ||||
Drug use ever before the start of the follow-up | ||||
Opioids | 20.3% (4419) | 24.6% (2678) | 1.28 (1.21–1.35) | 1.00 (0.95–1.06) |
Antipsychotics | 10.0% (2175) | 10.5% (1147) | 1.06 (0.98–1.15) | 0.99 (0.92–1.07) |
BZDRs | 34.8% (7583) | 45.4% (4952) | 1.56 (1.49–1.64) | 1.01 (0.96–1.07) |
Antidepressants | 13.5% (2942) | 21.2% (2315) | 1.73 (1.63–1.84) | 1.01 (0.94–1.08) |
Bisphosphonates | 13.4% (2915) | 14.3% (1560) | 1.08 (1.01–1.16) | 1.00 (0.93–1.07) |
Anti-parkinson drugs | 3.3% (727) | 3.8% (410) | 1.13 (1.00–1.28) | 1.00 (0.88–1.14) |
Antiepileptics | 7.5% (1636) | 8.9% (975) | 1.21 (1.11–1.32) | 1.00 (0.92–1.09) |
Analgesics | 78.9% (17,215) | 82.1% (8952) | 1.22 (1.15–1.30) | 1.01 (0.95–1.07) |
Cardiovascular drugs | 84.0% (18,328) | 85.5% (9327) | 1.12 (1.05–1.20) | 1.00 (0.94–1.07) |
Drug use at the start of the follow-up | ||||
Opioids | 3.9% (851) | 7.4% (805) | 1.96 (1.78–2.17) | 1.00 (0.90–1.11) |
Antipsychotics | 13.2% (2875) | 20.7% (2260) | 1.72 (1.62–1.83) | 1.00 (0.94–1.08) |
BZDRs | 16.9% (3696) | 31.0% (3379) | 2.20 (2.09–2.32) | 1.00 (0.92–1.08) |
Statistical analyses
Results
Number of events | Person years | Age-adjusted event rate per 100 person-years (95% CI) | Unadjusted HR (95% CI) | Adjusted HR (95% CI)a
| Propensity score adjusted HR (95% CI) | |
---|---|---|---|---|---|---|
Users compared with nonusers | ||||||
Nonusers | 981 | 47,423 | 2.43 (2.06–2.35) | Reference | Reference | Reference |
Users | 392 | 13,178 | 2.98 (2.49–3.06) | 1.38 (1.23–1.55) | 1.36 (1.21–1.53) | 1.35 (1.20–1.52) |
Antidepressant use classified according to duration of use | ||||||
1–30 days | 37 | 877 | 3.97 (2.70–5.25) | 2.15 (1.35–3.41) | 2.12 (1.33–3.36) | 1.71 (1.10–2.66) |
31–180 days | 102 | 3152 | 3.09 (2.49–3.70) | 1.27 (1.00–1.61) | 1.25 (1.00–1.59) | 1.35 (1.06–1.71) |
181–365 days | 84 | 2669 | 3.07 (2.41–3.73) | 1.35 (1.05–1.75) | 1.33 (1.03–1.72) | 1.35 (1.05–1.75) |
366–731 days | 90 | 3289 | 2.64 (2.10–3.18) | 1.29 (1.01–1.64) | 1.27 (1.00–1.62) | 1.28 (1.01–1.63) |
> 731 days | 79 | 3213 | 2.29 (1.56–3.01) | 1.50 (1.17–1.93) | 1.48 (1.15–1.91) | 1.35 (1.05–1.74) |
Drug class specific analyses (n = 38 concomitant users excluded) | ||||||
Other antidepressant | 110 | 4465 | 2.24 (1.78–2.71) | 1.01 (0.83–1.23) | 0.95 (0.77–1.16) | 0.94 (0.77–1.15) |
SSRI | 246 | 7664 | 2.74 (2.40–3.99) | 1.32 (1.15–1.52) | 1.28 (1.11–1.48) | 1.26 (1.10–1.45) |
As-treated analyses restricted to the first 180 days | ||||||
Nonusers | 248 | 9758 | 2.33 (2.03–2.63) | Reference | Reference | Reference |
Users | 139 | 4032 | 3.29 (2.74–3.84) | 1.36 (1.11–1.68) | 1.31 (1.06–1.62) | 1.34 (1.08–1.66) |
Intention-to-treat analyses restricted to the first 180 days | ||||||
Nonusers | 268 | 10,226 | 2.35 (2.05–2.65) | Reference | Reference | Reference |
Users | 173 | 5060 | 3.25 (2.76–3.75) | 1.31 (1.08–1.58) | 1.26 (1.03–1.53) | 1.34 (1.10–1.64) |
Number of events | Person years | Age-adjusted event rate per 100 person-years (95% CI) | Unadjusted HR (95% CI) | Adjusted HR (95% CI)a
| Propensity score adjusted HR (95% CI) | |
---|---|---|---|---|---|---|
Users compared with nonusers | ||||||
Nonusers | 492 | 47,514 | 1.10 (1.00–1.20) | Reference | Reference | Reference |
Users | 185 | 13,184 | 1.33 (1.13–1.53) | 1.30 (1.10–1.54) | 1.25 (1.05–1.49) | 1.26 (1.06–1.50) |
Antidepressant use classified according to duration of use | ||||||
1–30 days | 21 | 877 | 2.27 (1.29–3.25) | 2.13 (1.16–3.93) | 2.06 (1.12–3.80) | 2.06 (1.12–3.82) |
31–180 days | 46 | 3,154 | 1.39 (0.98–1.80) | 1.26 (0.88–1.78) | 1.21 (0.85–1.73) | 1.22 (0.85–1.73) |
181–365 days | 40 | 2,678 | 1.52 (1.04–2.00) | 1.25 (0.87–1.81) | 1.21 (0.84–1.75) | 1.21 (0.84–1.75) |
366–731 days | 47 | 3,291 | 1.38 (0.98–1.77) | 1.41 (1.01–1.96) | 1.35 (0.97–1.90) | 1.36 (0.97–1.90) |
> 731 days | 31 | 3,214 | 0.64 (0.26–1.02) | 1.11 (0.75–1.64) | 1.07 (0.72–1.58) | 1.07 (0.73–1.59) |
Drug class specific analyses (compared with nonuse, n = 38 concomitant users excluded) | ||||||
Other antidepressant | 50 | 4,461 | 1.08 (0.72–1.43) | 0.91 (0.68–1.22) | 0.87 (0.65–1.17) | 0.86 (0.64–1.15) |
SSRI | 114 | 7,671 | 1.31 (1.06–1.56) | 1.22 (0.99–1.49) | 1.21 (0.99–1.49) | 1.17 (0.95–1.44) |
As-treated analyses restricted to the first 180 days | ||||||
Nonusers | 117 | 9,759 | 1.13 (0.92–1.34) | Reference | Reference | Reference |
Users | 67 | 4,035 | 1.59 (1.20–1.97) | 1.38 (1.02–1.87) | 1.23 (0.90–1.67) | 1.26 (0.92–1.71) |
Intention-to-treat analyses restricted to the first 180 days | ||||||
Nonusers | 129 | 10,254 | 1.19 (0.98–1.40) | Reference | Reference | Reference |
Users | 89 | 5,084 | 1.66 (1.31–2.01) | 1.39 (1.06–1.83) | 1.28 (0.97–1.69) | 1.31 (1.00–1.73) |
Unadjusted OR (95% CI) | Adjusted OR (95% CI)a
| |
---|---|---|
Case window 1–14 days before the head injury | ||
Control window 30–45 days before | 1.77 (1.13–2.77) | 1.71 (1.09–2.68) |
Control window 60–74 days before | 1.67 (1.19–2.34) | 1.64 (1.17–2.30) |
Control window 120–134 days before | 2.04 (1.55–2.70) | 2.04 (1.55–2.70) |
Case window 1–14 days before the traumatic brain injury | ||
Control window 30–45 days before | 1.53 (0.83–2.82) | 1.46 (0.79–2.70) |
Control window 60–74 days before | 1.36 (0.85–2.16) | 1.33 (0.83–2.11) |
Control window 120–134 days before | 1.84 (1.24–2.73) | 1.81 (1.22–2.69) |