Data sourcesCochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Clinical Trials.gov and the WHO International Clinical Trials Registry Platform. There were no language restrictions.Study selectionRandomised controlled trials which compared the relief of pain with systemic antibiotics and analgesics against placebo and analgesics in the preoperative phase of irreversible pulpitis. The primary interest was pain control with an antibiotic or without one in the presence of analgesics. The secondary outcomes were type, dose and frequency of medication for pain relief and any adverse effects related to hypersensitivity or other reactions to either the antibiotic or analgesics.Data extraction and synthesisTwo authors independently assessed the results of the searches. Data extraction and risk bias assessment were also carried out independently. A third reviewer settled any disagreement on inclusion. Since only one study was included a meta-analysis could not be performed.ResultsOnly one double blind randomised clinical trial involving 40 participants with a diagnosis of irreversible pulpitis in one of their teeth was included in this review. This was a low risk, well-constructed double blind study. Half of the participants were treated with penicillin 500 mg, the other with a placebo every six hours over a seven- day period. In addition, all the participants were instructed to initially take one tablet of ibuprofen every 4-6 hours as needed and to take acetaminophen with codeine (two tablets every 4-6 hours) only if the ibuprofen did not relieve the pain.There was no significant difference in the mean total number of ibuprofen tablets over the study period; 9.2(standard deviation (SD) 6.02) in the penicillin group versus, 9.6 (SD 6.34) in the placebo group; mean difference -0.40 (95% CI -4.23 to 3.43); P value = 0.84.The mean total number of Tylenol tablets, 6.9 (SD 6.87), used in the penicillin group versus 4.45 (SD4.42) in the placebo group; mean difference 2.45 (95%CI -1.23 to 6.13; P value = 0.19). The study did not address adverse events.ConclusionsThere is insufficient evidence to accept or refute the benefit of using penicillin to control pain intensity associated with irreversible pulpitis. This study primarily found that antibiotics given preoperatively (before definitive root canal therapy) do not appear to significantly reduce toothache caused by irreversible pulpitis. Between the two groups, those taking the antibiotics and those taking the placebo, there was no statistical difference in the amount of oral analgesics taken to relieve the pain.