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Table 4 Unadjusted and adjusted hazard ratios for 6 adverse outcomes (falls, fracture, upper gastrointestinal bleed, road traffic accident, adverse drug reaction, and all-cause mortality) by antidepressant dose compared with periods of non-use of antidepressants over 5 years follow-up

From: Antidepressant use and risk of adverse outcomes in people aged 20–64 years: cohort study using a primary care database

    Unadjusted analysis Adjusted analysisc
Antidepressant class and dose categoriesa No of eventsb Person-yearsb Hazard ratio 95% CI Hazard ratio 95% CI P
Falls
 No current use 2493 558,933 1.00   1.00   
TCAs:
  ≤ 0.5 DDD 164 22,997 1.76 (1.49–2.08) 1.27 (1.07–1.50) 0.007
  > 0.5 DDD/≤ 1.0 DDD 64 8191 1.88 (1.50–2.37) 1.43 (1.13–1.80) 0.003
  > 1.0 DDD 46 5165 2.03 (1.50–2.75) 1.75 (1.30–2.36) < 0.001
 Test for trendd        0.009
SSRIs:
  ≤ 0.5 DDD 91 15,835 1.35 (1.09–1.67) 1.19 (0.96–1.47) 0.12
  > 0.5 DDD/≤ 1.0 DDD 1018 155,545 1.61 (1.49–1.73) 1.45 (1.35–1.57) < 0.001
  > 1.0 DDD 343 41,804 1.85 (1.65–2.08) 1.76 (1.56–1.98) < 0.001
 Test for trendd        0.001
Others:
  ≤ 0.5 DDD 20 3967 1.14 (0.74–1.75) 1.00 (0.65–1.53) 1.00
  > 0.5 DDD/≤ 1.0 DDD 86 13,046 1.62 (1.32–2.00) 1.38 (1.12–1.72) 0.003
  > 1.0 DDD 68 8274 1.90 (1.51–2.39) 1.75 (1.38–2.21) < 0.001
 Test for trendd        0.003
Fracture
 No current use 2759 510,172 1.00   1.00   
TCAs:
  ≤ 0.5 DDD 112 21,414 0.97 (0.81–1.16) 0.87 (0.72–1.05) 0.16
  > 0.5 DDD/≤ 1.0 DDD 47 7535 1.18 (0.89–1.56) 1.01 (0.76–1.36) 0.92
  > 1.0 DDD 27 4739 1.09 (0.76–1.58) 0.94 (0.65–1.38) 0.77
 Test for trendd        0.55
SSRIs:
  ≤ 0.5 DDD 97 14,710 1.26 (1.03–1.54) 1.21 (0.98–1.49) 0.07
  > 0.5 DDD/≤ 1.0 DDD 988 143,425 1.29 (1.19–1.40) 1.24 (1.15–1.35) < 0.001
  > 1.0 DDD 336 38,450 1.61 (1.44–1.80) 1.52 (1.35–1.70) < 0.001
 Test for trendd        0.004
Others:
  ≤ 0.5 DDD 25 3655 1.28 (0.86–1.91) 1.12 (0.74–1.69) 0.58
  > 0.5 DDD/≤ 1.0 DDD 90 11,805 1.39 (1.12–1.72) 1.25 (1.01–1.56) 0.04
  > 1.0 DDD 68 7525 1.66 (1.31–2.11) 1.48 (1.16–1.89) 0.001
 Test for trendd        0.08
Upper GI bleed
 No current use 588 570,654 1.00   1.00   
TCAs:
  ≤ 0.5 DDD 48 23,604 1.96 (1.45–2.64) 1.57 (1.15–2.14) 0.004
  > 0.5 DDD/≤ 1.0 DDD 15 8387 1.61 (0.94–2.74) 1.26 (0.74–2.14) 0.40
  > 1.0 DDD 8 5307 1.50 (0.74–3.03) 1.06 (0.50–2.27) 0.88
 Test for trendd        0.23
SSRIs:
  ≤ 0.5 DDD 19 16,165 1.11 (0.72–1.71) 1.20 (0.77–1.86) 0.43
  > 0.5 DDD/≤ 1.0 DDD 218 158,584 1.22 (1.04–1.44) 1.20 (1.01–1.42) 0.03
  > 1.0 DDD 55 42,780 1.28 (0.99–1.67) 1.08 (0.82–1.42) 0.58
 Test for trendd        0.83
Others:
  ≤ 0.5 DDD 5 4046 1.12 (0.46–2.70) 1.00 (0.41–2.41) 1.00
  > 0.5 DDD/≤ 1.0 DDD 20 13,234 1.56 (0.98–2.47) 1.12 (0.67–1.85) 0.66
  > 1.0 DDD 17 8398 2.00 (1.28–3.15) 1.54 (0.97–2.46) 0.07
 Test for trendd        0.89
Road traffic accident
 No current use 2343 546,915 1.00   1.00   
TCAs:
  ≤ 0.5 DDD 91 22,781 0.91 (0.74–1.13) 1.02 (0.82–1.27) 0.85
  > 0.5 DDD/≤ 1.0 DDD 28 8161 0.76 (0.50–1.17) 0.84 (0.55–1.30) 0.44
  > 1.0 DDD 25 5145 1.06 (0.69–1.62) 1.15 (0.75–1.76) 0.52
 Test for trendd        0.67
SSRIs:
  ≤ 0.5 DDD 57 15,607 0.87 (0.67–1.13) 0.94 (0.72–1.22) 0.62
  > 0.5 DDD/≤ 1.0 DDD 659 152,874 0.97 (0.89–1.06) 1.04 (0.95–1.14) 0.39
  > 1.0 DDD 176 41,186 0.99 (0.85–1.15) 1.03 (0.87–1.20) 0.76
 Test for trendd        0.64
Others:
  ≤ 0.5 DDD 14 3906 0.91 (0.53–1.55) 0.91 (0.53–1.58) 0.74
  > 0.5 DDD/≤ 1.0 DDD 52 12,828 0.90 (0.68–1.19) 0.98 (0.74–1.30) 0.90
  > 1.0 DDD 41 8158 1.15 (0.84–1.56) 1.23 (0.90–1.68) 0.20
 Test for trendd        0.21
Adverse drug reaction
 No current use 432 571,401 1.00   1.00   
TCAs:
  ≤ 0.5 DDD 71 23,632 3.10 (2.40–4.02) 2.59 (1.98–3.38) < 0.001
  > 0.5 DDD/≤ 1.0 DDD 18 8425 2.43 (1.47–4.02) 2.12 (1.28–3.51) 0.004
  > 1.0 DDD 19 5320 4.03 (2.51–6.49) 3.74 (2.32–6.01) < 0.001
 Test for trendd        0.79
SSRIs:
  ≤ 0.5 DDD 25 16,162 1.65 (1.09–2.49) 1.50 (0.99–2.27) 0.059
  > 0.5 DDD/≤ 1.0 DDD 304 158,743 1.97 (1.66–2.33) 1.81 (1.53–2.15) < 0.001
  > 1.0 DDD 51 42,866 1.58 (1.19–2.11) 1.46 (1.08–1.97) 0.013
 Test for trendd        0.36
Others:
  ≤ 0.5 DDD 11 4051 3.36 (1.87–6.03) 2.79 (1.51–5.16) 0.001
  > 0.5 DDD/≤ 1.0 DDD 28 13,281 2.54 (1.73–3.74) 2.35 (1.58–3.48) < 0.001
  > 1.0 DDD 18 8437 2.79 (1.72–4.53) 2.72 (1.68–4.43) < 0.001
 Test for trendd        0.58
All-cause mortality        
 No current use 1541 575,623 1.00   1.00   
TCAs:
  ≤ 0.5 DDD 180 23,895 2.77 (2.34–3.27) 1.77 (1.49–2.11) < 0.001
  > 0.5 DDD/≤ 1.0 DDD 69 8502 2.96 (2.30–3.80) 2.02 (1.55–2.62) < 0.001
  > 1.0 DDD 41 5363 2.89 (2.12–3.95) 1.92 (1.37–2.68) < 0.001
 Test for trendd        0.48
SSRIs:
  ≤ 0.5 DDD 81 16,289 1.85 (1.49–2.31) 1.57 (1.25–1.95) < 0.001
  > 0.5 DDD/≤ 1.0 DDD 663 159,847 1.56 (1.42–1.73) 1.32 (1.19–1.47) < 0.001
  > 1.0 DDD 195 43,226 1.67 (1.43–1.94) 1.40 (1.19–1.65) < 0.001
 Test for trendd        0.77
Others:
  ≤ 0.5 DDD 46 4100 4.15 (3.13–5.52) 2.59 (1.89–3.54) < 0.001
  > 0.5 DDD/≤ 1.0 DDD 87 13,404 2.48 (1.99–3.08) 1.61 (1.27–2.03) < 0.001
  > 1.0 DDD 47 8529 2.12 (1.60–2.80) 1.48 (1.10–1.99) 0.009
 Test for trendd        0.19
  1. aDaily doses could not be evaluated for some prescriptions
  2. bBased on numbers in adjusted analysis
  3. cAdjusted for age, sex, year of diagnosis of depression, severity of depression, deprivation, smoking status, alcohol intake, ethnic group (white/not recorded or non-white), coronary heart disease, diabetes, hypertension, cancer, epilepsy/seizures, hypothyroidism, osteoarthritis, asthma/chronic obstructive airways disease, rheumatoid arthritis, osteoporosis, liver disease, renal disease, obsessive-compulsive disorder, statins, NSAIDS, aspirin, antihypertensive drugs, anticonvulsants, hypnotics/anxiolytics, oral contraceptives, hormone replacement therapy, antipsychotics, bisphosphonates, anticoagulants; fracture outcome also adjusted for falls
  4. dTest for trend uses continuous values of dose
  5. DDD defined daily dose, GI gastrointestinal, SSRIs selective serotonin reuptake inhibitors, TCAs tricyclic and related antidepressants
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