Title	Combination Therapy of Acetaminophen and Ibuprofen Is the Most Effective Treatment for Patients with Post-Endodontic Pain
Clinical Question	In patients with post-operative endodontic pain, does the combination of non-steroidal anti-inflammatory drugs (NSAIDs) with acetaminophen provide more pain relief than individual NSAIDs or acetaminophen or placebo?
Clinical Bottom Line	For patients with post-operative endodontic pain, post-operative combination therapy of ibuprofen and acetaminophen provides more pain relief than acetaminophen alone or placebo. Acetaminophen alone did not provide more post-operative endodontic pain relief than placebo, suggesting that acetaminophen should only be used in combination with other NSAIDs for post-endodontic pain relief. Although meta-analysis indicated that ibuprofen-acetaminophen combination provided the most post-operative pain relief, combination therapy was not statistically more effective than ibuprofen alone. However, this may be due to the differences in dosages and study designs causing heterogeneity between the limited studies on post-endodontic pain included in meta-analysis.
Best Evidence
PubMed ID Author / Year Patient Group Study type (level of evidence) 27939729 Smith/2017 1,007 patients from 15 included studies with pre-operative pain who undergo endodontic treatment Systematic Review and Meta-Analysis Key results Meta-analysis demonstrated that ibuprofen (600 mg) was more efficacious at reducing pain compared to placebo at 6 hours post-procedure (mean difference = 10.5 points on visual analog scale (VAS)). Ibuprofen (600 mg) plus acetaminophen (1000 mg) was significantly more efficacious at reducing pain compared to placebo at 6 hours post procedure (mean difference = 34.89 VAS points). Although ibuprofen (600 mg) plus acetaminophen (1000 mg) caused a mean reduction of 13.94 VAS points compared to ibuprofen (600 mg) alone, this difference was not statistically significant. 27080115 Elzaki/2016 170 patients with moderate-severe pain from irreversible pulpitis with no evidence of apical periodontitis Randomized Controlled Trial Key results This study compared post-endodontic pain reduction in the first 8 hours post-procedure by paracetamol (1000 mg), also known as acetaminophen, compared to combinations of paracetamol (1000 mg) plus one additional NSAID - either ibuprofen (600 mg), mefenamic acid (500 mg) or diclofenac K (50 mg) – compared to placebo. All five treatment groups, including placebo, showed significant reductions in post-operative pain scores compared to pre-operative pain scores on the numerical rating scale 11 (NRS-11) pain scale and the visual rating scale 4 (VRS-4) (p < 0.001). The paracetamol-ibuprofen combination produced the greatest reduction in post-endodontic pain scores (p < 0.005) compared to pre-operative pain scores. When comparing between groups, the combinations of paracetamol-ibuprofen produced significantly greater pain reduction than paracetamol alone (p = 0.003) or placebo (p<0.005). Paracetamol-diclofenac K also produced significantly greater pain reduction than placebo (p<0.005). Interestingly, there was no significant difference in pain reduction between paracetamol alone and placebo (p=0.623).
Evidence Search	Endodontic pain nsaids acetaminophen
Comments on The Evidence	Validity: The main limitation of the systematic review and meta-analysis conducted by Smith and collaborators in 2017 was the lack of research studies on post-endodontic pain. Of the 15 studies that met inclusion criteria for the systematic review, only 5 studies could be analyzed by meta-analysis. Due to the limited number of studies included, there was substantial heterogeneity between studies based on differences in drugs tested, differences in drug dosages used, and differences in the timing of drug administration and pain measurements. Elzaki and co-investigators in 2017 conducted a double-blinded, randomized clinical trial (RCT) with appropriate blinding procedures with both positive and negative control drug comparisons. Although recall bias is unlikely, the participants were only evaluated for 8 hours post-endodontic procedure. There appear to be no conflicting interests for the authors. Perspective: Collectively, these studies provide strong support and rationale for prescribing combination therapy of acetaminophen and ibuprofen for post-endodontic pain. In the UTHSCSA Graduate Endodontic Clinic, endodontic patients are routinely prescribed the combination of 600 mg ibuprofen and 325 mg acetaminophen every 6 hours as needed for post-endodontic pain. Combining two anti-inflammatory drugs with different mechanisms of action would be more likely to provide better pain relief than monotherapy with minimal risks of toxicity and adverse effects.
Applicability	Collectively, the results of the meta-analysis and RCT are consistent with each other, and the major findings are relevant and applicable to patients experiencing post-endodontic pain. It is important to note that the Elzaki study was conducted in the Middle East, so ethnic and geographic factors might influence the applicability of these data to US patient populations.
Specialty	(Endodontics) (General Dentistry)
Keywords	Endodontics, pain, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen
ID#	3197
Date of submission	03/30/2017
E-mail	eskander@livemail.uthscsa.edu
Author	Michael A. Eskander, BS
Co-author(s)
Co-author(s) e-mail
Faculty mentor	Nikita Ruparel, DDS, MS, PhD
Faculty mentor e-mail	Ruparel@uthscsa.edu
Basic Science Rationale (Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?) None available
Comments and Evidence-Based Updates on the CAT (FOR PRACTICING DENTISTS', FACULTY, RESIDENTS and/or STUDENTS COMMENTS ON PUBLISHED CATs) None available