Cochrane review into paracetamol and hip and knee OA:(Leopoldino et al., 2019)
Little benefit at 12 weeks compared with placebo (dosage varying 1.95g/day to 4g/day); on average 3% difference between paracetamol and placebo
On VAS, pain reduced by 23 points on 0-100 scale with placebo, and 26 points with paracetamol, a 3% difference (clinically meaningful difference normally 9%)
Physical function improved by 12 points on 0-100 scale with placebo and 15 points with paracetamol, 3% difference; clinically meaningful difference estimated at 10%
Side effects: abnormal liver function occurred in 18/1000 participants with placebo and 70/1000 with paracetamol but clinical importance of this quoted as uncertain
Guidelines vary from conditional for use to conditional against use. Adjunct to core treatments
RACGP Guidelines NEUTRAL
Opioids in general (Tramadol and others) summary
-Opioids when compared to placebo have only small benefits on pain and function from 2-12 weeks of treatment
-contribute no measurable benefit to QOL, and
-show an increased risk of harms.
Strong opioids (hydromorphone, morphine, oxycodone, oxymorphone) inferior efficacy and overall worse safety than weak/intermediate opioids (codeine, tapentadol, hydrocodone, tramadol) (Osani et al., 2020)
Tramadol (Toupin April et al., 2019) Cochrane review-compared with placebo, moderate qulait evidence to show taking Tramadol for up to 3 months had no important benefit on mean pain or function, although slightly more people in tramadol group reported an important improvement than in placebo group.
Moderate quality evidence shows adverse events probably cause substantially more participants to stop Tramadol. Increase in serious adverse events less certain due to small number of events
(Zeng et al., 2019) Significantly higher mortality with Tramadol at one year compared with other meds
Non tramadol opioids (da Costa et al., 2014) Updated Cochrane review:
Opiods decrease pain intensity and improve function but small benefits. Out of 100 people, 10 will respond more to opioid than placebo, with an 1 point difference on pain scale (VAS out fo 10).
Out of 100 people, 8 more will respond to opioid more than placebo with a difference of 1 point in a 10 point disability scale.
Dose increases don’t appear to result in further pain reduction. Prolonging treatment seems to result in even smaller pain reduction. Effects on pain of questionable clinical relevance as 95% CI didn’t include minimal clinically important difference (0.9cm on 10cm VAS)
1.3% of participants who used opioids experienced side effects resulting in hospitalisation, persistent disability or death.
2.4% experienced withdrawal symptoms
Adverse events: occurred in 1 in 20 sufficient to stop participants taking medication
Opioids can create hyperalgesia
Recent systematic review and meta-analysis concluded: “Opioids provide minimal relief of OA symptoms within a 12 week period, and they are known to cause discomfort in a majority of patients. Clinicians and policy makers should reconsider the utility of opioids in the management of OA”
Guidelines vary but general consensus is either (i) consider if not had adequate response to other measures and not suitable for surgical management or (ii) conditional against.
RACGP OA Guidelines recommend STRONLY AGAINST both oral and transdermal opioids
Please see Western Australian government handout and recommendation on opioids
General recommendation is to take at lowest dose for shortest amount of time.
NSAIDs have a larger effect size on pain then paracetamol, and high quality guidelines concur on recommending NSAIDs (either strong for or conditional for).
However, NSAIDs have risk of side effects/adverse events, including GI bleeds and CV events.
Ibuprofen and naproxen may be preferred over diclofenac, as diclofenac associated with higher CV risk.
Co-morbidities need to be considered with taking NSAIDS, particularly GI and cardiovascular co-morbidities.
Topical NSAIDs can also be considered taking into account side effects, with guidelines varying in their recommendation from neutral to strong for.
The RACGP guidelines are conditional for oral NSAIDs and neutral for topical NSAIDs (due to lack of evidence)
Duloxetine (Cymbalta)
Thought that an imbalance of serotonin and noreipinephrine systems is a factor in central pain pathways and sensitization. Duloxetine is a selective serotonin and nor-adrelanine reuptake inhibitor (SNRI) that can be used in treatment of depression, also been used for fibromyalgia and diabetic peripheral neuropathic pain.
(Osani & Bannuru, 2019) found significant moderate effect on pain, function and QOL in knee OA patients however reported incidences of GI adverse events were approx. 4 times higher than with placebo.
A recent systematic review and meta-analysis of duloxetine for OA and chronic low back pain found Duloxetine had modest to moderate effects on pain relief, function improvement, mood regulation and improvement in quality of life. Adverse events were mild, and included decreased appetite, fatigue, nausea, hyperhidrosis, constipation and dry mouth (Weng, Wang et al 2020).
Most guidelines including RACGP are conditional for (as adjunct to core treatment)
TBC