What do systematic reviews say?

Sulodexide (heparin plus dermatan sulphate chains) vs prednisone

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes
  Sulodexide was without significant adverse events; one significant adverse event (gastritis) was reported for the prednisone group.
  1 study · 20 participants
  GRADE not reported

Bee propolis (one 500 mg capsule per day) vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 months (minimum)
  Propolis was associated with low rates of minimal side effects.
  1 study · 19 participants
  GRADE not reported

Individualised homeopathic medicine (two doses over 24 hours) vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 days
  A statistically significant difference was reported in mean pain score and mean ulcer size favouring the homeopathic group (P<0.05). Summary data not presented, precluding further analysis.
  1 study · 100 participants
  GRADE not reported

Subantimicrobial dose doxycycline (20 mg twice daily for 90 days) vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  90 days
  No differences in adverse events were reported.
  1 study · 50 participants
  GRADE not reported

Individualised homeopathic medicine (two doses over 24 hours) vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 days
  No participant needed to discontinue treatment due to adverse events.
  1 study · 100 participants
  GRADE not reported

Clofazimine (100 mg daily for 30 days, then 100 mg every other day) vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 months
  One trial at high risk of bias compared clofazimine (n=23) with placebo (n=20). The number of individuals in the clofazimine group who had no further aphthous episodes from beginning treatment until completion at 6…
  1 study · 43 participants
  GRADE not reported

LongoVital (herbal component alone) vs placebo

LongoVital (herbal component alone) showed no clear difference in number of days of pain (monthly average) compared with placebo; GRADE not reported.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  4 to 6 months
  MD -3.80 [-9.39, 1.79]
  1 study · 50 participants
  GRADE not reported

Beclometasone dipropionate (systemic corticosteroid) vs Placebo or no treatment

The review found no eligible studies for this question.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes
  Table 1: 'Studies of these corticosteroids were not found or included in the review but are included here for completeness.' No trial of beclometasone dipropionate for RAS was identified.
  0 studies
  No studies found

Vitamin B12 (sublingual, 1000 mcg daily for 6 months) vs placebo

Vitamin B12 (sublingual, 1000 mcg daily for 6 months) led to higher 'No ulcer' status during last 2 months of treatment compared with placebo; GRADE not reported.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 months
  RR 3.27 [1.23, 8.66]
  1 study · 58 participants
  GRADE not reported

Subantimicrobial dose doxycycline (20 mg twice daily for 90 days) vs placebo

Subantimicrobial dose doxycycline (20 mg twice daily for 90 days) showed no clear difference in number of ulcers at end of 90-day treatment compared with placebo; GRADE not reported.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  90 days
  MD -0.5 [-1.10, 0.10]
  1 study · 50 participants
  GRADE not reported

Colchicine (0.5 mg three times per day) vs Clofazimine (100 mg daily for 30 days, then 100 mg every other day)

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 months
  Clofazimine was associated with an increase in cutaneous adverse effects (Fisher's exact test P=0.015), easily controlled; there was a greater percentage of treatment interruptions in the colchicine group due to…
  1 study · 46 participants
  GRADE not reported

Perilla cooking oil vs Soybean cooking oil

Perilla cooking oil showed no clear difference in average number of days for resolution of ulcers compared with soybean cooking oil; GRADE not reported.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  8 months
  MD 0.80 [-1.83, 3.43]
  1 study · 33 participants
  GRADE not reported

Leukotriene receptor antagonist vs placebo

Montelukast (leukotriene receptor antagonist; 10 mg daily for 1… led to lower time to resolution of first ulcer (days) compared with placebo; GRADE not reported.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  2 months
  MD -3.95 [-4.38, -3.52]
  1 study · 40 participants
  GRADE not reported

LongoVital (herbal component alone) vs placebo

LongoVital (herbal component alone) showed no clear difference in mean size of ulcers compared with placebo; GRADE not reported.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  4 to 6 months
  MD -0.30 [-0.56, 0.04]
  1 study · 50 participants
  GRADE not reported

Pentoxifylline vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  60 days (plus 60-day follow-up)
  A single trial at high risk of bias compared pentoxifylline 400 mg three times daily (n=14) with placebo (n=12). No statistically significant differences were reported for pain, number of ulcers and ulcer-free days at…
  1 study · 26 participants
  GRADE not reported

Colchicine (0.5 mg three times per day) vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 months
  The trial by de Abreu 2009 (high risk of bias) also assessed colchicine (n=23) versus placebo (n=20). The number with no further aphthous episodes at 6 months was not significantly different from placebo (Fisher's…
  1 study · 43 participants
  GRADE not reported

Individualised homeopathic medicine (two doses over 24 hours) vs placebo

Individualised homeopathic medicine (two doses over 24 hours) led to higher pain free by end of study (day 6) compared with placebo; GRADE not reported.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 days
  RR 2.00 [1.39, 2.89]
  1 study · 100 participants
  GRADE not reported

Leukotriene receptor antagonist vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  2 months
  The study reported equal drug-related adverse effects for those treated with montelukast and placebo.
  1 study · 40 participants
  GRADE not reported

Thalidomide (immunomodulator) vs Placebo or no treatment

The review found no eligible studies for this question.

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes
  Authors' conclusions: 'this review did not find trials involving several of other systemic interventions used for RAS, for example thalidomide in the absence of any systemic condition, despite its limitations on…
  0 studies
  No studies found

Clofazimine (100 mg daily for 30 days, then 100 mg every other day) vs placebo

• Systemic interventions for recurrent aphthous stomatitis (mouth ulcers) 2012 · Cochrane All outcomes

  6 months
  Clofazimine was associated with an increase in cutaneous adverse effects (skin pigmentation and drying) (Fisher's exact test P=0.015), but these were reported to be easily controlled.
  1 study · 43 participants
  GRADE not reported