Opioids for osteoarthritis? Weighing benefits and risks: A Cochrane Musculoskeletal Group review

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Applied Evidence

Opioids for osteoarthritis? Weighing benefits and risks: A Cochrane Musculoskeletal Group review

J Fam Pract. 2011 April;60(4):206-212

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References

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TABLE 2
Tramadol for OA: Post-review RCTs are consistent with meta-analysis

Study duration (N)

Intervention groups

Primary outcome measures

Improvement in

Adverse effects

Pain

Global assessment

Function

Gana*²⁰ 12 wk (1020)

Tramadol ER
100 mg
200 mg
300 mg
400 mg

Placebo

WOMAC OA index (pain and physical function subscales)

100-mm VAS: Subject global disease

Treatment groups, 35%

Placebo, 25%

Treatment groups, 32%-36%

Placebo, 24%

Treatment groups, 31%-33%

Placebo, 22%

≥1 AE
Treatment groups, 71%-84% Placebo, 56%

Withdrawals due to AEs
Treatment groups, 20%-30% Placebo, 10%

Delemos*²¹ 12 wk (1001)

Tramadol ER
100 mg
200 mg
300 mg Celecoxib 200 mg

Placebo

WOMAC OA index (pain and physical function subscales)

100-mm VAS: Subject global disease

Tramadol, 27%-39%

Celecoxib, 45%

Placebo, 32%

Tramadol, 28%-40%

Celecoxib, 44%

Placebo, 30%

Tramadol, 26%-35%

Celecoxib, 43%

Placebo, 28%

≥1 AE
Tramadol, 63%-75% Celecoxib, 60% Placebo, 60%

Withdrawals due to AEs
Tramadol, 12%-31% Celecoxib,10% Placebo, 8%

Burch^†22 12 wk (646)

Tramadol (Contramid OAD) 100 mg titrating to 300 mg

Placebo

Pain intensity (11-point numerical scale)

Physician/patient global impressions of change (7-point scale)

Treatment group, 40%

Placebo, 33%

Treatment group, 80%

Placebo, 69%

NA

AEs
Treatment group: Nausea, 15.3%; constipation, 14.1%; dizziness/vertigo, 9.7%; somnolence, 6.7%

Placebo: Nausea, 5.6%; constipation, 4.2%; dizziness/vertigo, 3.7%; somnolence, 3.7%

Withdrawals due to AEs
Treatment group, 10% Placebo, 5%

Beaulieu*¹⁹ 6 wk (128)

Tramadol CR 200 mg titrating to 400 mg

Diclofenac SR 75 mg titrating to 150 mg

WOMAC OA index (pain and physical function subscales)

100-mm VAS: Pain intensity Subject global disease

Physician/patient global impressions of change (7-point scale)

Both groups, ~29%

Tramadol, 67%^‡

Diclofenac, 54%^‡

Tramadol, 29%^‡

Diclofenac, 29%^‡

Withdrawals due to AEs
Tramadol, 16% Diclofenac, 15%

*Hip or knee osteoarthritis.
^†Knee osteoarthritis.
^‡Not statistically significant.
AEs, adverse events; CR, controlled release; ER, extended release; NA, not assessed; OA, osteoarthritis; OAD, once a day; RCTs, randomized controlled trials; SR, sustained release; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities.

Oral and transdermal opioids: Pain relief but high risk
Among the patients with OA of the hip or knee—the study population for the review of oral and transdermal opioids—all the opioids tested were more effective than placebo. The benefits, however, were small to moderate, and were off set by large increases in the risk of AEs and a high dropout rate.

FAST TRACK

In the opioid review—which included trials of 4 oral opioids and transdermal fentanyl—the effect size was similar, regardless of analgesic potency or administration route.

Four of the 10 trials reported the number of patients experiencing any AE: 23% of those taking opioids vs 15% of patients on placebo.¹¹ This represents an NNH of 12 (TABLE 1). All 10 trials reported the number of patients who withdrew due to AEs. Those receiving opioids were 4 times as likely to withdraw due to AEs, compared with those taking placebo. The NNH to cause one additional withdrawal was 19 (95% CI, 13-29).

Bottom line

FAST TRACK

The American College of Rheumatology recommends tramadol for moderate-to-severe OA pain in patients who have contraindications or haven’t responded to COX-2-specific inhibitors and NSAIDs.

The data highlight both the limited role of opioids (including tramadol) in OA treatment and—when they are being considered for this patient population—the importance of making patients aware that the risks may outweigh the benefits. Used judiciously and with adequate patient counseling, tramadol may be an option when COX-2-specific inhibitors and NSAIDs fail or cannot be tolerated. Although the small-to-moderate benefits of non-tramadol opioids are generally outweighed by large increases in the risk of AEs, their use may be considered for severe OA pain if tramadol is ineffective or causes intolerable AEs.

CORRESPONDENCE
Faline Howes, BMedSci, MBBS, MPH, FRACGP, Menzies Research Institute Tasmania, Private Bag 23, University of Tasmania, Hobart, Tasmania, Australia 7001; Faline.Howes@ utas.edu.au