Cochrane · intervention · CD004715

Pharmacological interventions for pain in patients with temporomandibular disorders

Mujakperuo, HR, Watson, M, Morrison, R, et al. · Cochrane Database of Systematic Reviews · 2010 · Cochrane Library

Oral Health Oral and maxillofacial surgery Temporomandibular disorders and sleep2 versionsAMSTAR 2: not assessed

Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.

Questions

47

current version

GRADE rated

0

No studies

0

Included studies

11

as reported

No studies 0 · 0%Ungraded 47 · 100%Very low 0 · 0%Low 0 · 0%Moderate 0 · 0%High 0 · 0%

Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.

Review question

Element	Planned (methods)	Found (results)
Population	Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997), irrespective of race, gender, profession or residence; moderate to severe pain of minimum 3 months' duration. Excluded: patients without pain who had radiographic TMJ pathology plus deviation/clicking.	496 participants across 11 RCTs; most female (n=414, 83%); studies published 1983-2010; smallest 20, largest 83 participants
Intervention	A pharmacological agent, alone or in combination with other treatments for TMD; all routes except parenteral treatments.	Oral clonazepam (n=2); Oral gabapentin (n=1); Topical capsaicin (n=1); Oral diclofenac sodium (n=1); Oral naproxen (n=1); Oral celecoxib (n=1); Topical methyl salicylate (n=1); Oral cyclobenzaprine (n=1); Oral glucosamine hydrochloride/chondroitin sulphate (n=1); Oral piroxicam (n=1); Oral diazepam (n=1); Oral prazepam (n=1); Oral propranolol (n=1)
Comparison	Placebo, alone or in combination with other treatments for TMD	Placebo (n=11)
Outcomes	Patient-reported pain relief (VAS or validated categorical scale); patient global assessment of improvement, time to symptom relief, duration of symptom relief, overall quality of life, analgesic use; adverse events (types, participants affected, number of events, withdrawals)	Pain relief (n=11); Adverse events (n=10); Global assessment of improvement (n=2); Quality of life (n=1)
Study designs	Randomised controlled trials (quasi-randomised trials excluded)	Randomised controlled trials (n=11), all double-blind (parallel-group and one two-period cross-over)
Timing	Not specified	Trial duration: minimum 7 days, maximum 12 weeks, median 4 weeks

Search date: 2010-08. Databases: Cochrane Oral Health Group's Trials Register; CENTRAL; MEDLINE; EMBASE; CINAHL

Questions and results

Current version only

Oral clonazepam (benzodiazepine) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 6 questions

Outcome	Effect	Evidence	Status / GRADE
Participants' assessment of improvement of pain in right TMJ (VAS) 60 days same question in other reviews	MD -0.74 [-3.14, 1.66]	1 study · 20 participants	Ungraded
Jaw pain (VAS) 3 weeks same question in other reviews	MD -0.20 [-1.69, 1.29]	1 study · 41 participants	Ungraded
Pain on palpation of left masseter muscle (VAS) 60 days same question in other reviews	MD -0.89 [-2.46, 0.68]	1 study · 20 participants	Ungraded
Pain on palpation of right masseter muscle (VAS) 60 days same question in other reviews	MD -1.11 [-2.66, 0.44]	1 study · 20 participants	Ungraded
Participants' assessment of improvement of pain in left TMJ (VAS) 60 days same question in other reviews	MD -1.36 [-3.68, 0.96]	1 study · 20 participants	Ungraded
Adverse events (withdrawals due to adverse effects) 60 days same question in other reviews	One participant in the clonazepam group withdrew from the study by Harkins et al 1991 due to severe headache.	1 study · 20 participants	Ungraded

Oral gabapentin (anticonvulsant) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 4 questions

Outcome	Effect	Evidence	Status / GRADE
Spontaneous pain in the TMJ (VAS) 12 weeks same question in other reviews	MD -3.20 [-4.71, -1.69]	1 study · 44 participants	Ungraded
Participants' assessment of global function (VAS) 12 weeks same question in other reviews	MD -1.50 [-3.10, 0.10]	1 study · 44 participants	Ungraded
Number of tender sites on muscles of mastication (palpation index) 12 weeks same question in other reviews	MD -4.56 [-6.99, -2.13]	1 study · 44 participants	Ungraded
Adverse events (withdrawals due to adverse effects) 12 weeks same question in other reviews	Four of the participants withdrew from the study by Kimos et al 2007 due to adverse effects, but neither the type of adverse effect nor the trial group was specified.	1 study · 44 participants	Ungraded

Topical capsaicin (0.025% cream) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 4 questions

Outcome	Effect	Evidence	Status / GRADE
Adverse events (withdrawals due to adverse effects) 4 weeks same question in other reviews	Three participants from the topical capsaicin group withdrew from the study by Winocur et al 2000 due to the severity of the burning sensation and redness.	1 study · 30 participants	Ungraded
Pain on daily activity (VAS) 4 weeks same question in other reviews	MD -1.12 [-3.12, 0.88]	1 study · 30 participants	Ungraded
Maximum pain while on medication (VAS) 4 weeks same question in other reviews	MD -0.91 [-2.89, 1.07]	1 study · 30 participants	Ungraded
Present pain of TMD (VAS) 4 weeks same question in other reviews	MD -0.61 [-2.45, 1.23]	1 study · 30 participants	Ungraded

Oral diclofenac sodium (NSAID) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 5 questions

Outcome	Effect	Evidence	Status / GRADE
Adverse events (reported; mild, no withdrawals) 2 weeks same question in other reviews	Ekberg et al 1996 (diclofenac) reported adverse effects. Per the review's Adverse effects of interventions section: 'All but one study (Lobo et al 2004) reported adverse effects. Most of the reported adverse effects…	1 study · 32 participants	Ungraded
Pain at rest (not improved) 2 weeks same question in other reviews	RR 0.89 [0.46, 1.76]	1 study · 32 participants	Ungraded
Tenderness on palpation of three or more masticatory muscles 2 weeks same question in other reviews	RR 0.75 [0.34, 1.67]	1 study · 32 participants	Ungraded
Severe or very severe symptoms 2 weeks same question in other reviews	RR 0.88 [0.42, 1.84]	1 study · 32 participants	Ungraded
Daily pain (not improved) 2 weeks same question in other reviews	RR 0.71 [0.49, 1.04]	1 study · 32 participants	Ungraded

Oral naproxen (NSAID) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Pain intensity (VAS) 6 weeks same question in other reviews	MD -1.70 [-2.14, -1.25]	1 study · 68 participants	Ungraded
Adverse events (reported; mild, no withdrawals) 6 weeks same question in other reviews	Ta and Dionne 2004 (naproxen) reported adverse effects. Per the review: 'All but one study (Lobo et al 2004) reported adverse effects. Most of the reported adverse effects were mild and similar to the adverse effects…	1 study · 68 participants	Ungraded

Oral celecoxib (COX-2 inhibitor) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Pain intensity (VAS) 6 weeks same question in other reviews	MD 0.03 [-0.40, 0.45]	1 study · 68 participants	Ungraded
Adverse events (reported; mild, no withdrawals) 6 weeks same question in other reviews	Ta and Dionne 2004 (celecoxib) reported adverse effects. Per the review: 'All but one study (Lobo et al 2004) reported adverse effects. Most of the reported adverse effects were mild and similar to the adverse effects…	1 study · 68 participants	Ungraded

Topical methyl salicylate (Theraflex-TMJ) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Spontaneous masseter muscle pain (numerical graph rating scale) 15 days same question in other reviews	MD -2.00 [-2.38, -1.62]	1 study · 52 participants	Ungraded
Spontaneous TMJ pain (numerical graph rating scale) 15 days same question in other reviews	MD -0.90 [-1.35, -0.45]	1 study · 52 participants	Ungraded

Oral cyclobenzaprine (muscle relaxant) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Jaw pain (VAS) 3 weeks same question in other reviews	MD -1.30 [-2.67, 0.07]	1 study · 41 participants	Ungraded
Adverse events (reported; mild, no withdrawals) 3 weeks same question in other reviews	Herman et al 2002 (cyclobenzaprine) reported adverse effects. Per the review's Adverse effects of interventions section: 'All but one study (Lobo et al 2004) reported adverse effects. Most of the reported adverse…	1 study · 41 participants	Ungraded

Oral glucosamine hydrochloride/chondroitin sulphate vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 4 questions

Outcome	Effect	Evidence	Status / GRADE
Pain on TMJ palpation (ordinal scale) 3 months same question in other reviews	MD -0.30 [-3.09, 2.49]	1 study · 45 participants	Ungraded
Total pain rating index (McGill Pain Questionnaire) 3 months same question in other reviews	MD 1.60 [-8.29, 11.49]	1 study · 45 participants	Ungraded
Adverse events (withdrawals due to adverse effects) 3 months same question in other reviews	Two allergic reactions and one severe abdominal pain led to three withdrawals from the intervention group in the study by Nguyen et al 2001.	1 study · 45 participants	Ungraded
Pain intensity (VAS) 3 months same question in other reviews	MD -0.70 [-2.16, 0.76]	1 study · 45 participants	Ungraded

Oral piroxicam (NSAID) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Number of participants with severe dysfunction (pain of TMD not improved) 15 days same question in other reviews	RR 0.71 [0.29, 1.76]	1 study · 41 participants	Ungraded
Adverse events (reported; mild, no withdrawals) 15 days same question in other reviews	Roldan et al 1990 (piroxicam) reported adverse effects. Per the review's Adverse effects of interventions section: 'All but one study (Lobo et al 2004) reported adverse effects. Most of the reported adverse effects…	1 study · 41 participants	Ungraded

Oral diazepam (benzodiazepine) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 2 questions

Outcome	Effect	Evidence	Status / GRADE
Adverse events (reported; mild, no withdrawals) 15 days same question in other reviews	Roldan et al 1990 (diazepam) reported adverse effects. Per the review's Adverse effects of interventions section: 'All but one study (Lobo et al 2004) reported adverse effects. Most of the reported adverse effects were…	1 study · 41 participants	Ungraded
Number of participants with severe dysfunction (pain of TMD not improved) 15 days same question in other reviews	RR 0.67 [0.27, 1.66]	1 study · 41 participants	Ungraded

Oral prazepam (benzodiazepine) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 7 questions

Outcome	Effect	Evidence	Status / GRADE
No improvement in TMJ pain on external palpation 8 days · 5 mg prazepam same question in other reviews	RR 0.75 [0.47, 1.19]	1 study · 83 participants	Ungraded
No improvement in TMJ pain on external palpation 8 days · 10 mg prazepam same question in other reviews	RR 1.10 [0.68, 1.49]	1 study · 83 participants	Ungraded
No improvement in spontaneous TMJ pain 8 days · 10 mg prazepam same question in other reviews	RR 1.23 [0.81, 1.88]	1 study · 83 participants	Ungraded
No improvement in TMJ pain during mastication 8 days · 10 mg prazepam same question in other reviews	RR 1.18 [0.79, 1.77]	1 study · 83 participants	Ungraded
No improvement in spontaneous TMJ pain 8 days · 5 mg prazepam same question in other reviews	RR 0.79 [0.45, 1.38]	1 study · 83 participants	Ungraded
No improvement in TMJ pain during mastication 8 days · 5 mg prazepam same question in other reviews	RR 0.97 [0.61, 1.54]	1 study · 83 participants	Ungraded
Adverse events (reported; mild, no withdrawals) 8 days same question in other reviews	Rossi et al 1983 (prazepam) reported adverse effects. Per the review's Adverse effects of interventions section: 'All but one study (Lobo et al 2004) reported adverse effects. Most of the reported adverse effects were…	1 study · 83 participants	Ungraded

Oral propranolol (beta-blocker) vs Placebo

Population: Adult patients aged >=18 years, clinically or radiographically diagnosed with TMD (McNeill 1997 criteria); moderate to severe pain of minimum 3 months' duration

CD004715.PUB2 (current) · 5 questions

Outcome	Effect	Evidence	Status / GRADE
Adverse events (treatment-emergent) 1 week per period (cross-over) same question in other reviews	Tchivileva et al 2010: at least one treatment-emergent adverse event was reported by five participants (12.5%) during the propranolol period (nausea, diarrhoea, insomnia, dizziness, fatigue) and four participants (10%)…	1 study · 40 participants	Ungraded
Reduction in pain intensity (percentage of patients responding) 1 week per period (cross-over) same question in other reviews	Tchivileva et al 2010: a significantly greater percentage of patients (67.5% versus 32.5%) experienced reduction in pain intensity rating during the propranolol treatment period than the placebo treatment period (P =…	1 study · 40 participants	Ungraded
Reduction in pain duration (percentage of day) 1 week per period (cross-over) same question in other reviews	Tchivileva et al 2010: no statistically significant difference in reduction in pain duration (P = 0.802) between propranolol and placebo.	1 study · 40 participants	Ungraded
Change in pain index 1 week per period (cross-over) same question in other reviews	Tchivileva et al 2010: statistically significant difference in reduction in pain index between the propranolol treatment period and the placebo treatment period (P = 0.02).	1 study · 40 participants	Ungraded
Reduction in pain intensity rating 1 week per period (cross-over) same question in other reviews	Tchivileva et al 2010: Reduction in pain intensity rating (primary outcome) comparing propranolol treatment to placebo treatment did not reach statistical significance (P = 0.104); pairwise differences between…	1 study · 40 participants	Ungraded

Any pharmacological agent (opioid analgesic; NSAID/non-narcotic analgesic; steroid; muscle relaxant; CNS depressant; anti-anxiety/tranquillizing agent; antidepressant; antiepileptic; capsaicin), alone or with a non-pharmacological therapy vs Placebo

Population: Adults with temporomandibular disorders (TMD) diagnosed by clinical and/or imaging criteria (McNeil 1997); moderate to severe pain of minimum 3 months' duration

CD004715 · 1 question

Outcome	Effect	Evidence	Status / GRADE
Outcome NR	no estimate extracted	0 studies	No studies