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Table 5 Unadjusted and adjusted hazard ratios for six adverse outcomes (falls, fracture, upper gastrointestinal bleed, road traffic accident, adverse drug reaction, and all-cause mortality) by individual antidepressant drug compared with citalopram, 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 analysisb
Antidepressant drug No of eventsa Person yearsa Hazard ratio 95% CI Hazard ratio 95% CI P
Falls
SSRIs:
  Citalopram 628 92,765 1.00   1.00   
  Escitalopram 92 13,180 1.04 (0.84–1.28) 1.01 (0.82–1.25) 0.91
  Fluoxetine 539 80,665 1.02 (0.91–1.15) 0.99 (0.88–1.12) 0.92
  Paroxetine 115 16,322 1.06 (0.87–1.30) 1.05 (0.85–1.29) 0.65
  Sertraline 117 18,619 0.91 (0.74–1.13) 0.92 (0.74–1.15) 0.47
 TCAs:
  Amitriptyline 161 18,929 1.27 (1.07–1.50) 0.98 (0.83–1.16) 0.84
  Dosulepin 84 11,940 1.07 (0.83–1.37) 0.91 (0.70–1.17) 0.45
  Lofepramine 27 4709 0.87 (0.59–1.29) 0.79 (0.53–1.18) 0.25
  Trazodone 18 2335 1.22 (0.74–2.00) 0.98 (0.57–1.67) 0.94
Others:
  Mirtazapine 72 9959 1.12 (0.90–1.40) 0.97 (0.77–1.22) 0.78
  Venlafaxine 97 15,489 0.91 (0.74–1.12) 0.92 (0.75–1.13) 0.44
 All other antidepressants 31 4839 0.94 (0.67–1.32) 0.83 (0.59–1.18) 0.30
 Combined antidepressants 37 4121 1.26 (0.91–1.74) 1.08 (0.78–1.50) 0.65
 No current use 2493 558,933 0.62 (0.57–0.68) 0.67 (0.61–0.73) < 0.001
 Comparison between drugsc        0.98
Fracture
SSRIs:
  Citalopram 645 85,297 1.00   1.00   
  Escitalopram 90 12,193 0.95 (0.77–1.18) 0.97 (0.78–1.21) 0.82
  Fluoxetine 509 74,542 0.90 (0.80–1.01) 0.92 (0.82–1.04) 0.19
  Paroxetine 99 15,167 0.85 (0.69–1.05) 0.86 (0.70–1.07) 0.19
  Sertraline 121 17,149 0.94 (0.78–1.14) 0.95 (0.78–1.15) 0.59
TCAs:
  Amitriptyline 98 17,646 0.73 (0.60–0.90) 0.68 (0.55–0.83) < 0.001
  Dosulepin 59 11,075 0.70 (0.53–0.91) 0.67 (0.51–0.87) 0.003
  Lofepramine 28 4309 0.88 (0.62–1.25) 0.84 (0.58–1.20) 0.33
  Trazodone 15 2102 0.96 (0.59–1.57) 0.82 (0.50–1.35) 0.43
Others:
  Mirtazapine 73 8938 1.04 (0.81–1.32) 0.93 (0.73–1.19) 0.56
  Venlafaxine 106 14,174 0.96 (0.78–1.19) 0.96 (0.77–1.19) 0.68
 All other antidepressants 23 4472 0.71 (0.49–1.03) 0.63 (0.43–0.93) 0.020
 Combined antidepressants 29 3759 0.97 (0.65–1.45) 0.90 (0.60–1.35) 0.61
 No current use 2759 510,172 0.70 (0.64–0.76) 0.74 (0.67–0.81) < 0.001
 Comparison between drugsc        0.015
Upper GI bleed
SSRIs:
  Citalopram 110 94,862 1.00   1.00   
  Escitalopram 20 13,436 1.24 (0.76–2.03) 1.29 (0.78–2.12) 0.32
  Fluoxetine 123 82,236 1.28 (0.99–1.66) 1.24 (0.95–1.62) 0.11
  Paroxetine 26 16,569 1.28 (0.83–1.98) 1.17 (0.75–1.82) 0.49
  Sertraline 18 18,964 0.84 (0.52–1.35) 0.79 (0.48–1.30) 0.35
TCAs:
  Amitriptyline 35 19,565 1.60 (1.11–2.30) 1.29 (0.88–1.89) 0.19
  Dosulepin 22 12,178 1.63 (1.07–2.48) 1.31 (0.85–2.02) 0.22
  Lofepramine 7 4817 1.18 (0.51–2.71) 1.03 (0.45–2.36) 0.95
  Trazodone 10 2343 3.94 (2.13–7.26) 2.73 (1.44–5.17) 0.002
Others:
  Mirtazapine 19 10,154 1.75 (1.10–2.79) 1.19 (0.73–1.95) 0.48
  Venlafaxine 30 15,664 1.76 (1.19–2.58) 1.53 (1.03–2.27) 0.034
 All other antidepressants 9 4945 1.71 (0.90–3.25) 1.41 (0.72–2.78) 0.31
 Combined antidepressants 12 4245 2.49 (1.37–4.53) 2.04 (1.12–3.74) 0.020
 No current use 588 570,654 0.94 (0.76–1.16) 0.96 (0.78–1.19) 0.73
 Comparison between drugsc        0.08
Road traffic accident
SSRIs:
  Citalopram 398 91,139 1.00   1.00   
  Escitalopram 71 12,981 1.25 (0.96–1.64) 1.25 (0.95–1.64) 0.11
  Fluoxetine 311 79,365 0.91 (0.78–1.05) 0.86 (0.74–1.01) 0.06
  Paroxetine 78 16,030 1.11 (0.86–1.43) 1.05 (0.81–1.35) 0.73
  Sertraline 69 18,362 0.87 (0.69–1.10) 0.82 (0.64–1.06) 0.13
TCAs:
  Amitriptyline 85 18,784 1.04 (0.80–1.36) 1.05 (0.80–1.38) 0.72
  Dosulepin 35 11,855 0.68 (0.46–1.00) 0.70 (0.47–1.04) 0.08
  Lofepramine 20 4694 0.93 (0.56–1.56) 0.92 (0.55–1.52) 0.74
  Trazodone 7 2294 0.68 (0.33–1.41) 0.74 (0.35–1.55) 0.43
Others:
  Mirtazapine 50 9826 1.16 (0.88–1.52) 1.20 (0.91–1.58) 0.20
  Venlafaxine 60 15,179 0.94 (0.72–1.22) 0.87 (0.67–1.14) 0.31
 All other antidepressants 19 4777 0.90 (0.55–1.46) 0.93 (0.57–1.52) 0.77
 Combined antidepressants 18 4063 1.01 (0.64–1.59) 1.04 (0.66–1.65) 0.87
 No current use 2343 546,915 1.01 (0.90–1.13) 0.93 (0.82–1.04) 0.19
 Comparison between drugsc        0.045
Adverse drug reaction
SSRIs:
  Citalopram 163 94,933 1.00   1.00   
  Escitalopram 21 13,436 0.95 (0.61–1.48) 0.92 (0.58–1.45) 0.72
  Fluoxetine 134 82,362 0.95 (0.75–1.21) 0.92 (0.72–1.17) 0.51
  Paroxetine 36 16,608 1.20 (0.82–1.76) 1.23 (0.83–1.82) 0.29
  Sertraline 40 18,967 1.24 (0.91–1.70) 1.27 (0.92–1.74) 0.14
TCAs:
  Amitriptyline 66 19,635 1.94 (1.45–2.60) 1.73 (1.27–2.34) < 0.001
  Dosulepin 27 12,162 1.23 (0.80–1.88) 1.16 (0.75–1.81) 0.50
  Lofepramine 21 4819 2.39 (1.55–3.70) 2.40 (1.56–3.70) < 0.001
  Trazodone < 5 2372 0.50 (0.12–2.00) 0.49 (0.12–1.99) 0.32
Others:
  Mirtazapine 23 10,224 1.48 (0.92–2.37) 1.42 (0.88–2.31) 0.15
  Venlafaxine 40 15,689 1.72 (1.16–2.55) 1.75 (1.17–2.62) 0.006
 All other antidepressants 15 4949 1.81 (1.11–2.98) 1.71 (1.03–2.83) 0.038
 Combined antidepressants 11 4257 1.78 (0.98–3.24) 1.69 (0.92–3.09) 0.09
 No current use 432 571,401 0.54 (0.45–0.65) 0.58 (0.47–0.70) < 0.001
 Comparison between drugsc        < 0.001
All-cause mortality
SSRIs:
  Citalopram 405 95,640 1.00   1.00   
  Escitalopram 57 13,539 0.99 (0.77–1.26) 0.98 (0.75–1.27) 0.87
  Fluoxetine 347 82,935 1.00 (0.88–1.15) 1.04 (0.91–1.20) 0.56
  Paroxetine 64 16,705 0.93 (0.72–1.19) 0.94 (0.73–1.21) 0.64
  Sertraline 97 19,139 1.18 (0.96–1.46) 1.21 (0.97–1.50) 0.09
TCAs:
  Amitriptyline 194 19,845 2.28 (1.93–2.69) 1.77 (1.49–2.10) < 0.001
  Dosulepin 64 12,292 1.23 (0.95–1.60) 1.03 (0.78–1.35) 0.83
  Lofepramine 29 4863 1.42 (0.98–2.05) 1.18 (0.79–1.76) 0.42
  Trazodone 24 2390 2.30 (1.47–3.60) 1.49 (0.95–2.35) 0.08
Others:
  Mirtazapine 110 10,343 2.54 (2.07–3.11) 1.67 (1.33–2.09) < 0.001
  Venlafaxine 73 15,835 1.11 (0.88–1.42) 1.06 (0.83–1.36) 0.65
 All other antidepressants 48 5001 2.25 (1.68–3.02) 1.78 (1.32–2.38) < 0.001
 Combined antidepressants 41 4299 2.29 (1.68–3.12) 1.67 (1.21–2.31) 0.002
 No current use 1541 575,623 0.63 (0.57–0.71) 0.76 (0.68–0.85) < 0.001
 Comparison between drugsc        < 0.001
  1. aBased on numbers in adjusted analysis
  2. bAdjusted 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, stroke/TIA, 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
  3. cComparison is between the 11 individual drugs
  4. GI gastrointestinal, SSRIs selective serotonin reuptake inhibitors, TCAs tricyclic and related antidepressants
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