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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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