Withdrawals
outcome Reference Intervention Assessment time Outcome/effect size
Paracetamol-opioids vs nsaids – continued
Withdrawals due to 1 RCT (Parr et al. Dextropropoxyphene- 4 weeks 1.5% (dextro-para) and
respiratory AEs 1989) N=755 paracetamol vs slow-release 3.5% (diclofenac)
diclofenac Dextro-para better
Withdrawals due to 1 RCT (Parr et al. Dextropropoxyphene- 4 weeks 42% (dextro-para) and
CNS AEs 1989) N=755 paracetamol vs slow-release 23% (diclofenac)
diclofenac NSAID better
Total number of 1 RCT (Parr et al. Dextropropoxyphene- 4 weeks 17% (dextro-para) and
withdrawals 1989) N=755 paracetamol vs slow-release 15% (diclofenac)
diclofenac Both groups similar
Table 7.14 Withdrawals – continued
Pain outcome Reference Intervention Assessment time Outcome/effect size Knee
Opioid vs placebo
Pain relief (VAS) 1 MA (Bjordal et al. Opioids vs placebo 2–4 weeks Mean difference 10.5,
2007) 6 RCTs, 95% CI 7.4 to 13.7
N=1057 Favours opioids
Knee and/or hip Opioid vs placebo
Improvement in pain 1 RCT (Jensen and Tramadol vs placebo 2 weeks p=0.01
(verbal rating scale) Ginsberg 1994) Favours tramadol
during daily activities N=264
Improvement in pain 1 RCT (Jensen and Tramadol vs placebo 2 weeks p=0.006
(verbal rating scale) Ginsberg 1994) Favours tramadol
during walking N=264
Improvement in pain 1 RCT (Jensen and Tramadol vs placebo 2 weeks p=0.04
(verbal rating scale) Ginsberg 1994) Favours tramadol
during sleep N=264
Pain relief (VAS) 1 RCT (Jensen and Tramadol vs placebo 2 weeks NS Ginsberg 1994) N=264
Opioid-paraceatmol vs placebo
Pain intensity 1 MA (Cepeda et al. Tramadol/tramadol- Range 14–91 days Mean difference –8.47,
2006) 3 RCTs paracetamol vs placebo 95% CI –12.1 to –4.9,
p<0.00001
Favours opiod/opioid-paracetamol
Table 7.15 Symptoms: pain
continued
Pain outcome Reference Intervention Assessment time Outcome/effect size Knee and/or hip
Opiodis: low strength vs high strength
Total daily pain 1 RCT (Bird et al. Low dose tramadol vs 2 weeks (end of Cohort 1: NS
score (VAS) 1995) N=40, cohort 1 pentazocine treatment) Cohort 2: tramadol
(patients who took SS better
at least 1 dose in each period and had pain scores for at least 4 days Cohort 2 (patients who took at least 1 dose in each period and recorded pain scores on less than 4 days unless they withdrew due to lack of efficacy)
WOMAC pain, 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 107.2 (tramadol) and
change from 2006) (N=1020) treatment) 74.2 (placebo), p<0.01
baseline Favours tramadol
Arthritis pain intensity 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 27.8 (tramadol) and
in the index joint, 2006) (N=1020) treatment) 20.2 (placebo)
change from baseline Favours tramadol
WOMAC pain on 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of NS
walking on a flat 2006) (N=1020) treatment)
surface, change from baseline; Arthritis pain intensity in the non-index joint, change from baseline
WOMAC pain, 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 111.5 (tramadol) and
change from 2006) (N=1020) treatment) 74.2 (placebo), p<0.01
baseline Favours tramadol
WOMAC pain on 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 20.5 (tramadol) and
walking on a flat 2006) (N=1020) treatment) 13.6 (placebo), p<0.01
surface, change
from baseline Favours tramadol
Arthritis pain intensity 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 29.9 (tramadol) and
in the index joint, 2006) (N=1020) treatment) 20.2 (placebo), p<0.01
change from baseline Favours tramadol
Arthritis pain intensity 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 23.3 (tramadol) and
in the non-index 2006) (N=1020) treatment) 14.5 (placebo), p<0.01
joint, change from Favours tramadol
baseline
Table 7.15 Symptoms: pain – continued
continued
Pain outcome Reference Intervention Assessment time Outcome/effect size Knee and/or hip
Opiodis: low strength vs high strength – continued
WOMAC pain, 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 103.9 (tramadol) and
change from 2006) (N=1020) treatment) 74.2 (placebo), p<0.05
baseline Favours tramadol
WOMAC pain on 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 19.4 (tramadol) and
walking on a flat 2006) (N=1020) treatment) 13.6 (placebo), p<0.05
surface, change Favours tramadol
from baseline
Arthritis pain intensity 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 30.2 (tramadol) and
in the index joint, 2006) (N=1020) treatment) 20.2 (placebo), p<0.01
change from baseline Favours tramadol
Arthritis pain intensity 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 23.5 (tramadol) and
in the non-index 2006) (N=1020) treatment) 14.5 (placebo), p<0.01
joint, change from Favours tramadol
baseline
WOMAC pain, 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 107.8 (tramadol) and
change from 2006) (N=1020) treatment) 74.2 (placebo), p<0.01
baseline Favours tramadol
WOMAC pain on 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 19.7 (tramadol) and
walking on a flat 2006) (N=1020) treatment) 13.6 (placebo), p<0.05
surface, change Favours tramadol
from baseline
Arthritis pain intensity 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 28.0 (tramadol) and
in the index joint, 2006) (N=1020) treatment) 20.2 (placebo), p<0.01
change from baseline Favours tramadol
Arthritis pain intensity 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 21.3 (tramadol) and
in the non-index joint, 2006) (N=1020) treatment) 14.5 (placebo), p<0.05
change from baseline Favours tramadol
Table 7.15 Symptoms: pain – continued
Stiffness outcome Reference Intervention Assessment time Outcome/effect size Knee and/or hip
Opioids vs placebo
WOMAC stiffness, 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 43.0 (tramadol) and
change from baseline 2006) (N=1020) treatment) 32.2 (placebo), p<0.05
Favours tramadol WOMAC stiffness, 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 46.8 (tramadol) and
change from baseline 2006) (N=1020) treatment) 32.2 (placebo), p<0.01
Favours tramadol Table 7.16 Symptoms: stiffness
continued
Stiffness outcome Reference Intervention Assessment time Outcome/effect size Knee and/or hip
Opioids vs placebo – continued
WOMAC stiffness, 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 48.0 (tramadol) and
change from baseline 2006) (N=1020) treatment) 32.2 (placebo), p<0.01
Favours tramadol WOMAC stiffness, 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 45.0 (tramadol) and
change from baseline 2006) (N=1020) treatment) 32.2 (placebo), p<0.05
Favours tramadol Opioids: Low strength vs high strength
Morning stiffness 1 RCT (Bird et al. Low dose tramadol vs 2 weeks (end of p=0.034
duration 1995) N=40. pentazocine treatment) Favours tramadol
Morning stiffness 1 RCT (Bird et al. Low dose tramadol vs 2 weeks (end of NS
severity score. 1995) N=40. pentazocine treatment)
Table 7.16 Symptoms: stiffness – continued
Function outcome Reference Intervention Assessment time Outcome/effect size Knee and/or hip
Opioids vs placebo
Patient ratings of 1 RCT (Jensen and Tramadol vs placebo 2 weeks p=0.022
good or better in their Ginsberg 1994) N=264 Favours tramadol
overall assessment of treatment
Observers ratings of 1 RCT (Jensen and Tramadol vs placebo 2 weeks p=0.017
good or better in Ginsberg 1994) N=264 Favours tramadol
their overall assess-ment of treatassess-ment
Number of patients 1 RCT (Jensen and Tramadol vs placebo 2 weeks NS reporting improve- Ginsberg 1994) N=264
mentin: climbing stairs, getting out of bed and rising from a chair
WOMAC physical 1 RCT(Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 331.7 (tramadol) and
function, change from 2006) (N=1020) treatment) 234.3 (placebo), p<0.05
baseline (331.7 and Favours tramadol
234.3)
WOMAC total, change 1 RCT(Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 481.5 (tramadol) and
from baseline 2006) (N=1020) treatment) 340.5 (placebo), p<0.01
Favours tramadol Table 7.17 Symptoms: function
continued
Function outcome Reference Intervention Assessment time Outcome/effect size Knee and/or hip
Opioids vs placebo – continued
WOMAC physical 1 RCT(Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 350.2 (tramadol) and
function, change 2006) (N=1020) treatment) 234.3 (placebo), p<0.01
from baseline Favours tramadol
WOMAC total, 1 RCT(Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 510.0 (tramadol) and
change from baseline 2006) (N=1020) treatment) 340.5 (placebo), p<0.01
Favours tramadol WOMAC physical 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 336.1 (tramadol) and
function, change 2006) (N=1020) treatment) 234.3 (placebo), p<0.01
from baseline Favours tramadol
WOMAC total, 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 486.4 (tramadol) and
change from baseline 2006) (N=1020) treatment) 340.5 (placebo), p<0.01
Favours tramadol WOMAC physical 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 329.8 (tramadol) and
function, change 2006) (N=1020) treatment) 234.3 (placebo), p<0.05
from baseline Favours tramadol
WOMAC total, 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 479.2 (tramadol) and
change from baseline 2006) (N=1020) treatment) 340.5 (placebo), p<0.05
Favours tramadol Opioids/opioid-paracetamol vs placebo
At least moderate 1 MA (Cepeda et al. Tramadol/ tramadol- Range 14–91 days RR 1.4, 95% CI 1.2 to improvement in 2006) 4 RCTs, N=793 paracetamol vs placebo 1.6, p<0.00001
global assessment Favours tramadol
Opioids: Low strength vs high strength
Patient’s overall 1 RCT (Bird et al. Low dose tramadol vs 2 weeks (end of p=0.003
assessment of 1995) N=40. pentazocine treatment) Favours tramadol
treatment
Table 7.17 Symptoms: function
Global assessment
outcome Reference Intervention Assessment time Outcome/effect size
Knee and/or hip Opioids vs placebo
Physician’s global 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 22.9 (tramadol) and
assessment of 2006) (N=1020) treatment) 17.2 (placebo), p<0.05
disease activity, Favours tramadol
change from baseline
Table 7.18 Global assessment
continued
Global assessment
outcome Reference Intervention Assessment time Outcome/effect size
Knee and/or hip
Opioids vs placebo – continued
Patient’s global 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of NS
assessment of 2006) (N=1020) treatment)
disease activity
Physician’s global 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 22.4 (tramadol) and
assessment of 2006) (N=1020) treatment) 17.2 (placebo), p<0.01
disease activity, Favours tramadol
change from baseline
Patient’s global 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 21.8 (tramadol) and
assessment of 2006) (N=1020) treatment) 16.2 (placebo), p<0.01
disease activity Favours tramadol
Physician’s global 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 23.8 (tramadol) and
assessment of 2006) (N=1020) treatment) 17.2 (placebo), p<0.01
disease activity, Favours tramadol
change from baseline
Patient’s global 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 23.5 (tramadol) and
assessment of 2006) (N=1020) treatment) 16.2 (placebo), p<0.01
disease activity Favours tramadol
Physician’s global 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 22.9 (tramadol) and
assessment of 2006) (N=1020) treatment) 17.2 (placebo), p<0.05
disease activity, Favours tramadol
change from baseline
Patient’s global 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of NS
assessment of 2006) (N=1020) treatment)
disease activity
Opioids/opioid-paracetamol vs palcebo
At least moderate 1 MA (Cepeda et al. Tramadol/tramadol- Range 14–91 days RR 1.4, 95% CI 1.2 to improvement in 2006) 4 RCTs, N=793 paracetamol vs placebo 1.6, p<0.
global assessment Favours tramadol
Table 7.18 Global assessment – continued
QoL outcome Reference Intervention Assessment time Outcome/effect size Knee and/or hip
Opioids vs placebo
Sleep quality, 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of All p<0.05
trouble falling asleep, 2006) (N=1020) treatment) Favours tramadol
awakened by pain in the night and in the morning, the need for sleep medication
SF-36 physical and 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of NS
mental components, 2006) (N=1020) treatment)
change from baseline
Sleep quality, trouble 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of All p<0.05
falling asleep, 2006) (N=1020) treatment) Favours tramadol
awakened by pain in the night and in the morning
SF-36 physical and 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of NS
mental components; 2006) (N=1020) treatment)
The need for sleep medication, change from baseline
Sleep quality, trouble 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of All p<0.05
falling asleep, 2006) (N=1020) treatment) Favours tramadol
awakened by pain in the night and in the morning
SF-36 physical and 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of NS
mental components; 2006) (N=1020) treatment)
The need for sleep medication, change from baseline
Sleep quality, trouble 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of All p<0.05
falling asleep, 2006) (N=1020) treatment) Favours tramadol
awakened by pain in the night
SF-36 physical and 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of NS
mental component; 2006) (N=1020) treatment)
Being awakened by pain in the morning;
The need for sleep medication, change from baseline
Table 7.19 Quality of life
Adverse events and withdrawals as
outcome Reference Intervention Assessment time Outcome/effect size
Knee and/or hip Opioids vs placebo
Withdrawal rate 1 MA (Bjordal et al. Opiodis vs placebo Not mentioned Opioids had high
2007) withdrawal rates
(20–50%)
Withdrawals due 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 14% (tramadol) and
to AEs 2006) (N=1020) treatment) 10% (placebo)
Favours placebo Number of patients 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 71% (tramadol) and
reporting at least 2006) (N=1020) treatment) 56% (placebo)
1 AE Favours placebo
Number of patients 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 1.5% (tramadol) and
reporting at least 2006) (N=1020) treatment) 1% (placebo)
1 SAE Favours placebo
Withdrawals due 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 20% (tramadol) and
to AEs 2006) (N=1020) treatment) 10% (placebo)
Favours placebo Number of patients 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 73% (tramadol) and
reporting at least 2006) (N=1020) treatment) 56% (placebo)
1 AE Favours placebo
Number of patients 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 2% (tramadol) and
reporting at least 2006) (N=1020) treatment) 1% (placebo)
1 SAE Favours placebo
Withdrawals due 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 26% (tramadol) and
to AEs 2006) (N=1020) treatment) 10% (placebo)
Favours placebo Number of patients 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 76% (tramadol) and
reporting at least 2006) (N=1020) treatment) 56% (placebo)
1 AE Favours placebo
Number of patients 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 1.5% (tramadol) and
reporting at least 2006) (N=1020) treatment) 1% (placebo)
1 SAE Favours placebo
Withdrawals due 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 29% (tramadol) and
to AEs 2006) (N=1020) treatment) 10% (placebo)
Favours placebo Number of patients 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 84% (tramadol) and
reporting at least 2006) (N=1020) treatment) 56% (placebo)
1 AE Favours placebo
Number of patients 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 3% (tramadol) and
reporting at least 2006) (N=1020) treatment) 1% (placebo)
1 SAE Favours placebo
Table 7.20 Adverse events and withdrawals
continued
Adverse events and withdrawals as
outcome Reference Intervention Assessment time Outcome/effect size
Knee and/or hip
Opioids/opioid-paracetamol vs placebo
Minor AEs 1 MA (Cepeda et al. Tramadol/tramadol- Range 14–91 days Mean difference 2.17, 2006) 4 RCTs, N=953 paracetamol vs placebo 95% CI 1.8 to 2.7,
p<0.00001 Favours placebo Opioids: low strength vs high strength
Percentage of 1 RCT (Jensen and High dose tramadol vs 2 weeks (end of All p≤0.001 patients experiencing Ginsberg 1994) dextropropoxyphene study) Favours
AEs, nausea, vomiting N=264 dextropropoxyphene
and the percentage of withdrawals due to AEs
Percentage of 1 RCT (Jensen and High dose tramadol vs 2 weeks (end of NS patients experiencing Ginsberg 1994) dextropropoxyphene study)
constipation N=265
Numbers of patients 1 RCT (Bird et al. Low dose tramadol vs 2 weeks (end of No p-values given
with AEs and nausea, 1995) N=40 pentazocine treatment) Favours tramadol
patient withdrawals due to AEs and treatment failure
Number of patients 1 RCT (Bird et al. Low dose tramadol vs 2 weeks (end of No p-values given
who experienced 1995) N=40 pentazocine treatment) Favours pentazocine
vomiting and diarrhoea
Table 7.20 Adverse events and withdrawals – continued
Rescue medication
outcome Reference Intervention Assessment time Outcome/effect size
Knee and/or hip Opioids vs placebo
Rescue medication 1 RCT (Gana et al. Tramadol 100 mg vs placebo 12 weeks (end of 3% (tramadol) and
use 2006) (N=1020) treatment) 7% (placebo)
Favours tramadol Rescue medication 1 RCT (Gana et al. Tramadol 200 mg vs placebo 12 weeks (end of 3% (tramadol) and
use 2006) (N=1020) treatment) 7% (placebo)
Favours placebo Rescue medication 1 RCT (Gana et al. Tramadol 300 mg vs placebo 12 weeks (end of 1.5% (tramadol) and
use 2006) (N=1020) treatment) 7% (placebo); p<0.05
Favours placebo Rescue medication 1 RCT (Gana et al. Tramadol 400 mg vs placebo 12 weeks (end of 2.5% (tramadol) and
use 2006) (N=1020) treatment) 7% (placebo); p<0.05
Favours placebo Table 7.21 Rescue medication