Table 1 Characteristics of included studies

Alcoff et al. [51]

50 participants with subacute and chronic LBP; mean age imipramine group 29.2 years, placebo group 33.8 years^b; n = 24 (48%) female

USA; 2 sites

2

Oral imipramine 75 for 3 days, 150 thereafter, n = 28

Placebo, n = 22

8 weeks

SBPQ, BDI

Atkinson et al. [52]

121 participants with chronic LBP; mean age 46.4 (10.2) years; n = 47 (38.8%) female

USA

7

Oral desipramine target concentrations of 50 ng/mL n = 17, or 110 ng/mL n = 17, or 150 ng/mL n = 18, or fluoxetine target concentrations of 50 ng/mL n = 14, or 100 ng/mL n = 14, or 150 ng/mL n = 15

Active placebo (benztropine mesylate) n = 26

12 weeks

DDS, BDI, RMDQ

Atkinson et al. [62]

103 participants with chronic LBP; mean age 49.2 (9.4) years; n = 38 (37%) female

USA

3

Oral maprotiline 150, n = 33, or paroxetine 30, n = 34

Active placebo (diphenhydramine) 37.5, n = 36

8 weeks

DDS, BDI

Atkinson et al. [63]

78 participants with chronic LBP; mean age nortriptyline group 45.79 (10.59) years, placebo group 47.13 (10.65) years; n = 0 (0%) female

USA

2

Oral nortriptyline 25 for 3 days, 50 for 4 days, 75 for 3 days, 100 for 4 days to reach target concentration of 50–150 ng/ml, n = 38

Placebo, n = 40

8 weeks

DDS, BDI

Dickens et al. [64]

92 participants with chronic LBP. Mean age 45 years^b; n = 50 (54%) female

UK

2

Oral paroxetine 20, n = 44

Placebo, n = 48

8 weeks

100 mm VAS, MADRS

Goodkin et al. [65]

42 participants with chronic LBP; mean age 53.6 (12.9) years; n = 16 (38%) female

USA

2

Oral trazodone 50, increasing to 600, n = 22

Placebo, n = 22

6 weeks

100 mm VAS, BDI

Gould et al. [66]

142 participants with chronic LBP; mean age 55.8 (11.7) years; n = 15 (11 %) female

USA

4

Oral desipramine hydrochloride to reach target concentration of 5–60 ng/ml, n = 37, or desipramine hydrochloride to reach target concentration of 5–60 ng/ml and cognitive behavioral therapy, n = 37

Active placebo (benztropine mesylate) 0.125 and cognitive behavioral therapy, n = 33, or active placebo (benztropine mesylate) 0.125, n = 32

12 weeks

DDS, RMDQ

Jenkins et al. [67]

59 participants with acute and chronic LBP; mean age imipramine group 26 years, placebo group 26.7 years^b; n = 3 (5%) female

UK

2

Oral imipramine 75, n = 30

Placebo, n = 29

4 weeks

10 cm VAS, BDI

Johnson et al. [68] (crossover)

14 participants with chronic LBP; mean age 36.93 (13.05) years; n = 0 (0%) female

USA

2

Oral duloxetine, 30 for 1 week, titration to 60 for 2 weeks, then maintenance for 4 weeks, 30 for final week, n = 7 ^a

Placebo, n = 7^a

8 weeks/phase with 1-week washout

BPI

Katz et al. [69] (crossover)

54 participants with chronic LBP; mean age 50.6 (10.7) years; n = 21 (48%) female^c

USA

2

Oral bupropion 150 for 3 days, 300 until end week 5, 150 until week 7, n = 21^a

Placebo, n = 23^a

7 weeks/phase with 2-week washout

11-point NRS, BDI, RMDQ

Konno et al. [53]

458 participants with chronic LBP; mean age 58.9 (13.4) years; n = 237 (52%) female

Japan; 58 sites

2

Oral duloxetine 20 first week, 40 second week, 60 weeks 3–14, n = 232

Placebo, n = 226

14 weeks

11-point NRS, RMDQ

NCT00227292 (withdrawn)

Chronic LBP

Germany

2

Oral escitalopram 10 for 1 week, 20 for 3 weeks

Placebo

4 weeks

VAS, HDRS

NCT01225068

40 participants with chronic neuropathic LBP; mean age 47.7 (10.3) years; n = 21 (52%) female

USA

2

Oral milnacipran 100, option to increase to 200 after 2 weeks, n = 20. Drug escalated in week 1 and discontinued after week 6

Placebo, n = 20

6 weeks

100 mm VAS

NCT03249558 (ongoing)

Chronic LBP or chronic neck pain

USA

3

Oral morphine 60 plus duloxetine, or morphine plus placebo duloxetine, or placebo morphine plus duloxetine 60

Placebo

10 weeks

VAS

NCT03364075 (crossover; terminated)

Chronic LBP

NR

3

Oral duloxetine 30 for 1 week then 60 for 1 week plus placebo, or propranolol 40 for 1 week then 60 for 1 week plus placebo, or duloxetine 30 for 1 week then 60 for 1 week plus propranolol 40 for 1 week then 60 for 1 week

Placebo

2 weeks/phase with 1-week washout

Pain index

Pheasant et al. [54] (crossover)

16 participants with chronic LBP; mean age 47.2 years^b; n = 16 (75%) female

USA

2

Oral amitriptyline 50, n = 6^a

Active placebo (atropine) 0.2, n = 10^a

6 weeks/phase with 2-week washout

Functional evaluation rating

Schliessbach et al. [55] (crossover)

50 participants with chronic LBP; mean age 54.4 (17.3) years; n = 32 (64%) female

Switzerland

2

Oral imipramine 75  single dose, n = 50

Active placebo (tolderodine) 1.0, single dose, n = 50

2 h/phase with 1-week washout

11-point NRS

Schukro et al. [56] (crossover)

41 participants with chronic LBP and leg pain; mean age 57.9 years (13.4); n = 21 (51%) female

Austria

2

Oral duloxetine 30 to 60 first week; 60 to 120 second week; 120 for 2 weeks, n = 16^a

Placebo, n = 18^a

4 weeks/phase with 2-week washout

10 cm VAS, BDI, RMDQ

Skljarevski et al. [57]

236 participants with chronic LBP, mean age duloxetine groups 51.8 (14.9) years; placebo group 51.2 (13.5) years; n = 144 (61%) female

18 clinical sites in Brazil, France, Germany, Mexico, and Netherlands

2

Oral duloxetine 30 for 1 week, 60 for 6 weeks, non-responders increased to 120/day for remainder of study, n = 115

Placebo, n = 121

13 weeks

11-point NRS, BDI-II, RMDQ

Skljarevski et al. [58]

404 participants with chronic LBP; mean age duloxetine 20 mg group 52.9 (12.8) years, duloxetine 60 mg group 53.3 (14.7) years, duloxetine 120 mg group 54.9 (14.8) years, placebo group 54 (13.5) years; n = 232 (57%) female

NR

4

Oral duloxetine 20, n = 59, or 60, n = 116, or 120, n = 112

Placebo, n = 117

13 weeks

11-point NRS, BDI-II, RMDQ

Skljarevski et al. [59]

401 participants with chronic LBP, mean age duloxetine group 54.9 (13.7) years; placebo group 53.4 (14.2) years; n = 246 (61%) female

27 sites in Germany, Netherlands, Poland, Russia, Spain, and USA

2

Oral duloxetine 60, n = 198

Placebo, n = 203

12 weeks

11-point NRS, BDI-II, RMDQ

Treves et al. [60]

68 participants with chronic LBP, LBP with leg pain, and sciatica; mean age 45.6^b years; n = 35 (51%) female

France

3

IV clomipramine, progressive doses in the morning until maximum dose of 75 reached (3rd day) and maintained for the next 7 days with placebo in evening, n = 25, or IV clomipramine progressive doses in the evening until maximum dose of 75 reached (3rd day) and maintained for the next 7 days with placebo in morning, n = 27

IV placebo (isotonic glucose), n = 16

10 days

10 cm VAS

Urquhart et al. [61]

146 participants with chronic LBP; mean age amitriptyline group 53.5 (14.2) years, placebo group 56.0 (13.2) years; n = 56 (38.%) female

Australia

2

Oral amitriptyline 25, n = 72

Active placebo (benztropine mesylate) 1.0, n = 74

6 months

100 mm VAS, BDI, RMDQ