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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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