What do systematic reviews say?

Full-mouth disinfection (FMD): scaling/root planing (subgingival instrumentation) of all quadrants within 24 hours plus adjunctive antiseptic (chlorhexidine) treatments (rinsing, pocket irrigation, tongue/tonsil brushing) vs Quadrant scaling and root planing (control): SRP of each quadrant in separate sessions at least one week apart

• Full‐mouth treatment modalities (within 24 hours) for periodontitis in adults 2022 · Cochrane All outcomes
  13 studies provided adverse-event/participant-reported information; 3 reported an event after FMD or FMS; most important harm was increased body temperature. FMD/chlorhexidine-specific harms reported by Fonseca 2015…
  13 studies
  GRADE not reported

Full-mouth scaling (FMS): scaling/root planing (subgingival instrumentation) of all quadrants within 24 hours, without antiseptic vs Quadrant scaling and root planing (control): SRP of each quadrant in separate sessions at least one week apart

• Full‐mouth treatment modalities (within 24 hours) for periodontitis in adults 2022 · Cochrane All outcomes
  13 studies provided adverse-event/participant-reported information; 3 reported an event after FMD or FMS; most important harm was increased body temperature after treatment. Narrative, not separated by comparison and…
  13 studies
  GRADE not reported

Doxycycline + SRP vs Metronidazole + SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included studies have not reported adverse events
  Studies not reported
  No studies found

Amoxicillin + clavulanate + SRP vs Tetracycline + SRP

Amoxicillin + clavulanate + SRP showed no clear difference in adverse events compared with tetracycline + SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  The only included trial (Abu Fanas 1991) reported there were no adverse events.
  1 study · 8 participants
  GRADE not reported

Clindamycin + SRP vs SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Metronidazole + SRP vs Amoxicillin + metronidazole + SRP

Metronidazole + SRP showed no clear difference in adverse events compared with amoxicillin + metronidazole + SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  All three included trials (Matarazzo 2008; Silva 2011; Xajigeorgiou 2006) reported adverse events in both MTZ + SRP and AMOX + MTZ + SRP groups (nausea, vomiting, diarrhoea, headache, metallic taste, irritability, mild…
  3 studies · 84 participants
  GRADE not reported

Amoxicillin + metronidazole + SRP vs Clarithromycin + SRP

Amoxicillin + metronidazole + SRP showed no clear difference in adverse events compared with clarithromycin + SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  Two patients were reported to have vomiting and unbearable stomach pain in the AMOX + MTZ + SRP group (Araujo 2019).
  1 study
  GRADE not reported

Clarithromycin + SRP vs SRP

Clarithromycin + SRP showed no clear difference in adverse events compared with SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  Both included trials reported adverse events in the clarithromycin + SRP group: unpalatable taste and mild gastric intolerance in 2 patients (Pradeep 2011); mild gastrointestinal discomfort in 2 patients (Rebelatto…
  Studies not reported
  GRADE not reported

Metronidazole + SRP vs SRP

It is very uncertain whether metronidazole + SRP changes adverse events compared with SRP (very low certainty).

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  No severe adverse effects were reported by any of the participants in 1 study. 2 studies have not reported adverse events.
  3 studies · 71 participants
  Very low

Tetracycline + SRP vs SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Doxycycline + SRP vs SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Clindamycin + SRP vs Metronidazole + SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Azithromycin + SRP vs SRP

It is very uncertain whether azithromycin + SRP changes adverse events compared with SRP (very low certainty).

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  1 study reported diarrhoea, headache or dizziness, metallic taste, and general unwellness by 4 participants from the intervention group and 3 from the control group. In 1 study none of the participants reported any…
  2 studies · 110 participants
  Very low

Amoxicillin + metronidazole + SRP vs SRP

It is very uncertain whether amoxicillin + metronidazole + SRP changes adverse events compared with SRP (very low certainty).

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Most common adverse events were mild gastrointestinal disturbances, nausea and vomiting, metallic taste, and diarrhoea in the intervention group. Control group reported adverse events like hypothermia, mild…
  2 studies · 389 participants
  Very low

Clindamycin + SRP vs Doxycycline + SRP

The review found no eligible studies for this question.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes

  Long-term (≥ 1 year)
  Included study has not reported adverse events
  Studies not reported
  No studies found

Doxycycline + SRP vs Amoxicillin + metronidazole + SRP

Doxycycline + SRP showed no clear difference in adverse events compared with amoxicillin + metronidazole + SRP; GRADE not reported.

• Adjunctive systemic antimicrobials for the non‐surgical treatment of periodontitis 2020 · Cochrane All outcomes
  One trial (Akincibay 2008) did not report this outcome; Xajigeorgiou 2006 reported mild gastrointestinal discomfort in 2 subjects from the AMOX + MTZ + SRP group.
  1 study
  GRADE not reported

Enamel matrix derivative (EMD; Emdogain) vs Guided tissue regeneration (GTR) with barriers

Enamel matrix derivative (EMD; Emdogain) led to lower postoperative complications (infection) / adverse events compared with guided tissue regeneration (GTR) with barriers; GRADE not reported.

• Enamel matrix derivative (Emdogain®) for periodontal tissue regeneration in intrabony defects 2009 · Cochrane All outcomes

  1 year (time-points 1, 5 and 10 years planned)
  RR 0.12 [0.02, 0.85]
  3 studies
  GRADE not reported

Enamel matrix derivative (EMD; Emdogain) vs Various bone grafting (BG) procedures (animal-derived or synthetic bone / bioactive ceramic filler)

• Enamel matrix derivative (Emdogain®) for periodontal tissue regeneration in intrabony defects 2009 · Cochrane All outcomes

  1 year (time-points 1, 5 and 10 years planned)
  Complications and other adverse events: none occurred.
  1 study
  GRADE not reported

Enamel matrix derivative (EMD; Emdogain) vs placebo or control

• Enamel matrix derivative (Emdogain®) for periodontal tissue regeneration in intrabony defects 2009 · Cochrane All outcomes

  1 year (time-points 1, 5 and 10 years planned)
  No particular adverse events or infection attributable to EMD in any trial; no differences in pain, edema, hematoma, wound dehiscence or root sensitivity (Tonetti 2002).
  9 studies
  GRADE not reported