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Review

Analgesic Efficacy of Postoperative Ibuprofen in Third Molar Surgery: A Meta-Analysis

by
Itzel Joselyn Mora-Falcón
1,
Iván Agustín Amador-Beas
1,
Ronell Bologna-Molina
2,3,
Nelly Molina-Frechero
4,
Othoniel Hugo Aragón-Martínez
5,
Nicolás Serafín-Higuera
6,
Sandra López-Verdín
7 and
Mario Alberto Isiordia-Espinoza
1,*
1
Departamento de Clínicas, Centro Universitario de los Altos, División de Ciencias Biomédicas, Universidad de Guadalajara, Tepatitlán de Morelos 47620, Mexico
2
Departamento de Patología Molecular, Facultad de Odontología, Universidad de la República (UDELAR), Montevideo 11200, Uruguay
3
Departamento de Investigación, Facultad de Odontología, Universidad Juárez Autónoma de Durango, Durango 34000, Mexico
4
Laboratorio de Cariología y Medicina Oral, Departamento de Salud, Universidad Autónoma Metropolitana-Xochimilco, Ciudad de Mexico 04960, Mexico
5
Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí 78290, Mexico
6
Centro de Ciencias de la Salud Mexicali, Facultad de Odontología Mexicali, Universidad Autónoma de Baja California, Mexicali 21040, Mexico
7
Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico
*
Author to whom correspondence should be addressed.
Oral 2025, 5(3), 72; https://doi.org/10.3390/oral5030072
Submission received: 30 July 2025 / Revised: 28 August 2025 / Accepted: 4 September 2025 / Published: 18 September 2025
(This article belongs to the Topic Advances in Dental Health, 2nd Edition)
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Versions Notes

Abstract

Purpose: The aim of this study is to determine the analgesic efficacy of ibuprofen 200, 400, and 600 mg after lower third molar surgery. Material and Methods: Clinical trials that included patients undergoing third molar surgery comparing ibuprofen with placebo were included. The only exclusion criteria was loss of postoperative patient follow-up greater than 20%. PubMed, Wiley, Science Direct, EBSCOhost, Scopus, and Web of Science databases were used to search for clinical trials. The risk of bias of the included articles was assessed using the Cochrane Collaboration’s seven-point risk of bias tool, and dichotomous data for the most important variables for determining analgesic efficacy and adverse effects were then concentrated into one database for statistical analysis. Results: The qualitative analysis was performed with 57 clinical trials and a total of n = 7735 patients. Moreover, the number of patients who took rescue analgesics and the global evaluation of the studied drugs showed statistical differences in favor of ibuprofen 200 (n = 797 and n = 694, respectively), 400 (n = 2803 and n = 2407, respectively), and 600 mg (n = 1149 and n = 291, respectively) compared to placebo. Adverse effects, such as nausea, vomiting, and headache, resulted in statistical differences in favor of ibuprofen 200 (n = 1461, n = 1319, and n =1342, respectively), 400 (n = 3917, n = 3124, and n = 2477, respectively), and 600 mg (n = 716) in comparison to placebo. The numbers needed to treat indicated high efficacy of ibuprofen in controlling pain after third molar surgery, while the numbers needed to harm were high, indicating the good safety profile of this drug. Conclusions: Ibuprofen has high analgesic efficacy and a good safety profile when used after third molar surgery.

1. Introduction

Postoperative pain is the main challenge for a general dentist or maxillofacial surgeon after performing impacted lower third molar surgery [1,2]. This phenomenon is dictated by the trauma of the soft and bony tissues of the peri-surgical region [3,4,5,6,7,8], as well as other factors, such as the patient’s adherence to postoperative indications for managing inflammatory complications set by the clinicians [9,10,11] and their knowledge of pharmacological options to meet the needs of each case [12,13,14,15,16,17,18].
Pain after third molar surgery occurs in the immediate postoperative period [5,17]. According to the clinical characterization of this postoperative pain model, peak pain occurs between 5 and 8 h postoperatively. However, episodes of pain can continue to occur at any time during the first 24 h postoperatively [5,17,18]. Third molar surgery is usually performed under local anesthesia, which facilitates pain assessment. It is usually rapid in onset and has mild-to-moderate intensity, affecting the patient’s quality of life [17].
Conventional postoperative pharmacological treatment after lower third molar surgery consists of using mainly three types of medications: nonsteroidal anti-inflammatory pain drugs (NSAIDs) [15,16,17], opioid analgesics [18], and glucocorticoids [14,19]. Undoubtedly, the main group of drugs used to control pain and other postsurgical complications after third molar surgery is NSAIDs [20].
Recently, a quantitative systematic review evaluated the analgesic effectiveness of ibuprofen and traditional NSAIDs in oral surgery [20]. However, the pooled data comparisons were limited due to the number of drugs and the doses used for each [20]. On the other hand, in clinical research, it is essential to compare the effect of an analgesic drug with a placebo to determine its analgesic efficacy [21].
This systematic review aims to synthesize information reported in clinical trials on the analgesic effectiveness of the postoperative administration of ibuprofen compared to placebo following lower third molar surgery.

2. Materials and Methods

This systematic review was carried out according to the PRISMA guidelines [22,23], and the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (2011) [24].

2.1. Selection Criteria

Inclusion criteria (PICO) [25]:
Population: Patients undergoing third molar surgery.
Interventions: Ibuprofen administered postoperatively (200 mg, 400 mg, and 600 mg).
Control: Postoperative administration of placebo.
Outcome: The number of patients requiring rescue analgesic medication, overall evaluation of study treatments (patient satisfaction), and adverse effects.
Exclusion criteria: Loss of postoperative patient follow-up greater than 20%.

2.2. Search Using Databases

Clinical trials published from January 1990 to May of this year were considered for inclusion in this systematic review. The PubMed, Wiley, Science Direct, EBSCOhost, Scopus, and Web of Science databases were utilized to read the abstracts of those studies that were located with the following keywords: “Ibuprofen”, “placebo”, “third molar surgery”; “third molar removal”, “wisdom teeth surgery”, “wisdom teeth removal”, “wisdom teeth extraction”, “oral surgery”, “third molar extraction”, and “dental extraction”.
The PubMed search was conducted using study types “Clinical Trial”, “Randomized Controlled Trial”, “Controlled Clinical Trial”, and “Clinical Study”, and published in English or Spanish. In Wiley Online Library, the publication type (“Journals”) and Subjects (“Dentistry”) filters were used. The ScienceDirect search was limited to “research articles” (article type), areas of “Medicine and Dentistry”, and “Pharmacology, Toxicology and Pharmaceutical Sciences”. At EBSCOhost, the search was filtered only by “scholarly publications” (source type). In Scopus, the search was filtered by three areas: “Medicine”, “Dentistry”, and “Pharmacology, Toxicology, and Pharmaceutics”; “Article” was selected as the document type, “Journal” as the source, and “Human” only as the keyword. Finally, in Web of Science, the information was filtered by document type (“article”) and Web of Science category (“Dentistry, Oral Surgery, Medicine”, “Pharmacology, Pharmacy”, “Surgery”, “General Internal Medicine” and “Anesthesiology”). In all databases, only articles in English and Spanish were considered. This review was registered in the PROSPERO database—University of York (ID: CRD42025649382).

2.3. Assessment of Bias

The Cochrane Collaboration’s seven-point risk of bias tool was utilized [20,26,27,28,29].

2.4. Data Extraction

The data were initially concentrated in an Excel file and subsequently transferred to statistical software for analysis in this study. The number of patients requiring rescue analgesic medication, overall evaluation of study treatments (the total of patients reporting a global assessment as good, very good, or excellent), and adverse effects—nausea, dizziness, vomiting, or headache—were extracted.
When a clinical trial assessed the efficacy of a dose (e.g., ibuprofen 200 mg) using two or more dosage forms (e.g., tablets, capsules, soluble tablets, etc.), the data were summed and concentrated in the statistical analysis as a single data point that was used for comparison with placebo.
Two academics independently searched for clinical trials indicating a comparison between ibuprofen and placebo in third molar surgery, conducting a risk of bias assessment and data extraction. The disagreements between two professors thoroughly examined, and a consensus was ultimately reached with the facilitation of a third researcher [30,31,32].

2.5. Statistical Analysis

The number of patients requiring rescue analgesic medication and the overall evaluation of the study treatments (patient satisfaction) were analyzed using the random effects method due to the high heterogeneity observed (I2 test > 30%) [24,28,29,33,34]. On the other hand, the data analysis on adverse effects showed low heterogeneity, so the fixed effects model was used (I2 test < 30%) [24,28,29,33,34]. The Mantel-Haenszel test, the Odds Ratio (OR), and the confidence intervals (CIs) were calculated—estimators of the effect size—using the Review Manager 5.3 software for Windows. Moreover, the number needed to treat (NNT), the number needed to harm (NNH), and the CIs were obtained using the Risk Reduction Calculator (University of Illinois) [35,36,37]. A p-value of <0.05 in the overall test and an OR > 1 was considered a statistical difference [28,29,34]. Using data from the variables rescue analgesia and global treatment assessment, publication bias was assessed by visual inspection of funnel plots [24].

3. Results

3.1. Database Search

In the databases consulted for the search, 8993 articles were found. After removing articles unrelated to the topic, the duplicated articles, and performing a screening of the articles, 71 articles were obtained for a complete evaluation. During the full review, 9 articles that did not use placebo as a comparison group were discarded and 5 additional articles were eliminated because they did not meet the PICO criteria. Only 57 articles were included in the qualitative analysis and 49 clinical trials provided data for the quantitative analysis (meta-analysis) of this systematic review (Figure 1) [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94].

3.2. Evaluation of Bias

The risk of bias assessment showed that 54 studies scored low to moderate risk of bias [38,39,40,42,43,44,45,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,86,87,88,89,90,91,92,93,94] while only 3 studies scored high risk of bias (Figure 2) [41,46,85].

3.3. Qualitative Analysis

The qualitative characteristics of 57 clinical trials were assessed to determine the analgesic effectiveness and adverse effects of ibuprofen 200 (n = 994), 400 (n = 3143), and 600 mg (n = 805) compared to placebo (n = 2793) following, at least, a third molar surgery [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94]. The total number of participants in this qualitative analysis was n = 7735 (Table S1) [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94].
Ibuprofen 400 mg was the most commonly used in the trials included in this systematic review [38,39,40,41,43,47,50,51,52,54,55,56,57,59,60,61,63,64,66,68,69,70,71,72,73,74,75,76,77,78,79,80,81,83,84,85,86,87,88,92,93,94] followed by ibuprofen 200 mg [40,46,49,50,51,53,58,59,60,67,73,75,77,83,86,89,90], and finally ibuprofen 600 mg [42,44,45,48,62,65,69,82,86,91]. A total of 19 trials performed the surgical procedure using local anesthesia alone [38,39,40,44,52,57,58,61,62,63,68,69,73,79,80,82,83,90,91], 28 studies used sedation/general anesthesia [41,43,45,47,48,49,50,51,53,54,55,59,60,65,66,70,72,76,78,81,84,85,86,87,88,89,92,94], and 10 trials did not report these data [42,46,56,64,67,71,74,75,77,93]. On the other hand, 14 studies used paracetamol, an NSAID or an opioid analgesic as monotherapy [43,44,49,52,58,62,64,65,66,79,82,83,86,90], 27 clinical trials used a combination of an NSAID and an opioid analgesic [41,42,45,47,48,50,54,55,57,59,60,68,69,70,71,72,76,77,78,81,84,85,88,89,92,93,94], and 16 articles did not report this information (Table S1) [38,39,40,46,51,53,56,61,63,67,73,74,75,80,87,91].

3.4. Quantitative Analysis

The number of patients taking rescue analgesics after third molar surgery who received ibuprofen 200 mg and placebo was evaluated in 7 clinical trials [49,53,59,60,77,86,89]. Evaluation of the pooled data shows that fewer patients in the ibuprofen 200 mg group needed to take rescue analgesics compared with the placebo group (n = 797, I2 = 0%, Z = 7.97, OR = 0.20, 95% CIs = 0.13 to 0.29, p = 0.00001, Figure 3). Moreover, 24 clinical studies assessed ibuprofen 400 mg compared to the placebo [38,39,41,43,47,57,59,60,64,68,69,70,71,72,76,77,79,84,85,86,87,88,93,94]. The pooled data analysis showed that fewer patients in the ibuprofen 400 mg group took rescue analgesics compared to placebo (n = 2803, I2 = 56%, Z = 8.98, OR = 0.21, 95% CIs = 0.15 to 0.30, p = 0.00001, Figure 3). The number of patients requiring rescue analgesics with ibuprofen 600 mg and placebo was assessed using data from 9 articles [42,44,45,48,62,65,69,82,86]. The result was similar to that obtained with the two previous doses of ibuprofen, indicating a decrease in the number of patients requiring rescue medication compared to the placebo group (n = 1149, I2 = 72%, Z = 3.84, OR = 0.26, 95% CIs = 0.13 to 0.52, p = 0.0001, Figure 3). The NNT and CIs can be seen in Table 1.
The overall evaluation of ibuprofen 200 mg was performed with data from 6 clinical trials [49,59,60,77,86,89] while that of ibuprofen 400 mg was conducted with 20 studies [39,41,47,57,59,60,66,69,70,71,72,76,77,80,84,85,86,87,88,94], and ibuprofen 600 mg was made using 2 clinical trials [42,86]. The pooled results show that ibuprofen 200 (n = 694), 400 (n = 2407), and 600 mg (n = 291) resulted in better patient scores when compared to the placebo group (Figure 4). The NNT and CIs can be seen in Table 1.

3.5. Adverse Effects

Data from 13 articles were used to evaluate the adverse effects of ibuprofen 200 mg and placebo [40,46,49,51,53,59,60,73,75,77,83,89,90]. The pooled analysis shows that ibuprofen caused a decrease in nausea (n = 1461, I2 = 0%, Z = 3.14, OR = 0.48, 95% CIs = 0.31 to 0.76, p = 0.002; Figure 5) [40,46,49,51,53,59,60,75,77,83,89,90], vomiting (n = 1319, I2 = 0%, Z = 2.24, OR = 0.51, 95% CIs = 0.29 to 0.92, p = 0.02; Figure 5) [40,46,49,53,59,60,73,75,77,89,90], and headache (n = 1342, I2 = 0%, Z = 2.72, OR = 0.53, 95% CIs = 0.34 to 0.84, p = 0.007; Figure 5) [40,46,49,51,53,59,60,75,77,83,90] when compared to placebo. The NNH and CIs can be seen in Table 1.
Data from 28 clinical trials were used to assess the adverse effects of ibuprofen 400 mg and placebo [39,40,41,43,47,51,54,55,57,59,60,66,70,71,72,73,74,75,76,77,80,81,83,84,85,87,92,93]. The results showed that ibuprofen significantly decreased the number of patients reporting nausea (n = 3917, I2 = 0%, Z = 3.51, OR = 0.65, 95% CIs = 0.51 to 0.83, p = 0.0004; Figure 6) [39,40,41,43,47,51,54,55,57,59,60,66,70,71,72,74,75,76,77,80,81,83,84,85,92,93], vomiting (n = 3124, I2 = 0%, Z = 3.14, OR = 0.61, 95% CIs = 0.45 to 0.83, p = 0.002; Figure 6) [40,41,43,47,59,60,66,70,71,72,74,75,76,77,81,84,87,92,93], and headache (n = 2477, I2 = 0%, Z = 2.95, OR = 0.58, 95% CIs = 0.41 to 0.84, p = 0.003; Figure 6) when compared to placebo [40,41,43,47,51,54,55,57,59,60,70,72,75,77,81,83,84,85,87]. The NNH and CIs can be seen in Table 1.
Data from 4 clinical trials were used to assess the adverse effects of ibuprofen 600 mg and placebo (n = 822) [42,45,48,82]. A pooled analysis shows that vomiting and headache were decreased in the ibuprofen group compared with placebo (n = 716, I2 = 0%, Z = 2.98, OR = 0.19, 95% CIs = 0.07 to 0.57, p = 0.003, and n = 716, I2 = 0%, Z = 3.65, OR = 0.27, 95% CIs = 0.13 to 0.54, p = 0.0003, respectively; Figure 7) [42,45,48].

3.6. Assessment of Publication Bias

The funnel plot for rescue analgesic use shows slight asymmetry, suggesting potential publication bias. The OR close to 0.1 indicates that the treatment results in a significant reduction in rescue analgesic use (a). On the other hand, the funnel plot for the overall treatment assessment shows that the studies are dispersed, but center on an OR of 10. This OR demonstrates that ibuprofen has significant and robust efficacy (b) (Figure 8).

4. Discussion

This systematic review analyzed the qualitative data from 57 studies and quantitative data from 49 clinical trials to determine the size of the analgesic effect of three doses of ibuprofen in comparison to placebo. The qualitative analysis showed that ibuprofen 400 mg was the most commonly used in the trials included in this systematic review [38,39,40,41,43,47,50,51,52,54,55,56,57,59,60,61,63,64,66,68,69,70,71,72,73,74,75,76,77,78,79,80,81,83,84,85,86,87,88,92,93,94], followed by ibuprofen 200 mg [40,46,49,50,51,53,58,59,60,67,73,75,77,83,86,89,90] and, finally, ibuprofen 600 mg [42,44,45,48,62,65,69,82,86,91]. Moreover, the pooled results show that ibuprofen substantially reduced the number of patients requiring rescue analgesia postoperatively compared with placebo. The overall assessment of the treatments showed that a greater number of patients rated ibuprofen as good, very good, and excellent compared to placebo. Both indicators of analgesic efficacy had high heterogeneity, so the statistical analysis was performed with a conservative approach using the random effects model. In this regard, the NNTs for the number of patients requiring rescue analgesics and global evaluation of the study drugs were low, close to NNT = 3, indicating that ibuprofen could be a highly efficient treatment with important clinical value after third molar surgery [95,96].
Franco-de la Torre et al., 2021 [20] conducted a systematic review and meta-analysis to compare the analgesic effect of ibuprofen in comparison with other analgesic treatments following third molar surgery. Although it was possible to compare ibuprofen with aspirin, bromfenac, and low doses of diclofenac, the sample size was small. In addition, analysis using pooled data of ibuprofen compared to other drugs was not feasible for the most part [20]. Due to these challenges, it was impossible to determine the NNT, NNH, or CIs in the systematic review by Franco-de la Torre et al., 2021 [20]. We decided to carry out this study to achieve larger sample sizes, which would allow for the calculation of these clinically important analgesic efficacy indicators, as well as to summarize existing information on the analgesic efficacy and adverse effects of ibuprofen 200, 400, and 600 mg following third molar surgery, so that the expert clinicians can have it available for implementation in clinical practice and/or to avoid its use.
Without a doubt, ibuprofen 400 mg was the most used dose in the clinical trials included in this systematic review, followed by ibuprofen 200 mg and then ibuprofen 600 mg. According to some authors, ibuprofen 400 mg is considered the “gold standard” analgesic treatment for the treatment of pain after third molar surgery [94]. Considering the above, clinicians must have highly relevant data such as NNT, NNH, and CIs at their disposal. This is one of several clinical studies our group is conducting to determine the indicators of the clinical utility—NNT, NNH, and CIs—of NSAIDs in third molar surgery so that physicians can become familiar with them and decide which one to use based on availability in their office or hospital or determine which drug they recommend in their private consultation.
Ibuprofen is considered the safest non-selective NSAID for the COX-2 enzyme [97]. Its main adverse effects occur in the gastrointestinal system and the kidneys [98,99]. Franco-de la Torre et al., 2021, in their systematic review and meta-analysis, evaluated the adverse effects of ibuprofen without distinguishing the type of adverse reaction, considering only the number of patients who reported adverse effects for each treatment [20]. In our systematic review, a statistical analysis was performed using pooled data of the most encountered adverse effects—nausea, dizziness, vomiting, and headache—in the included clinical trials. The results show that ibuprofen 200, 400, and 600 mg produced fewer adverse effects compared to placebo after the third molar extraction. Furthermore, in this systematic review, the NNH of ibuprofen was high, confirming the clinical safety of ibuprofen in oral surgery in relation to the severity of adverse effects found in the clinical trials included in the statistical analysis. It is important to note that none of the studies included in this systematic review reported serious adverse effects [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94].
The main advantage of our study was the number of clinical trials included in both the qualitative and quantitative analyses. This entails a series of important points that we would like to highlight, such as the sample size achieved with all the included studies, which in turn provides greater robustness to the statistical analysis that demonstrated the NNT and NNH of ibuprofen 200, 400, and 600 mg, which had not been previously calculated specifically for third molar surgery. A bias assessment was performed, which revealed that most of the clinical trials included in this review exhibited high methodological rigor and yielded statistics that could be utilized by clinicians in their daily practice (NNT and NNH). The main disadvantage of this study was that some clinical trials did not provide data because they did not evaluate the variables of interest or presented the variable, but measured it on a measurement scale different from that established in our methodology. Another important limitation of this study is that a subgroup analysis was not performed considering the ibuprofen administration schedule (single-dose or multiple-doses), nor comparing the different pharmaceutical presentations of ibuprofen.
In conclusion, the statistical analysis in this systematic review and meta-analysis demonstrates that ibuprofen has high analgesic efficacy and a good safety profile when used after third molar surgery. Furthermore, the results of this meta-analysis could be considered a guide for the clinical use of ibuprofen 200, 400, and 600 mg after third molar surgery.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/oral5030072/s1, Table S1: Sociodemographic characteristics, treatments, and specifications of the surgical procedure.

Author Contributions

All authors made substantial contributions to the conception of this review. M.A.I.-E., S.L.-V. and O.H.A.-M. conceived and designed the study. M.A.I.-E., R.B.-M. and I.J.M.-F. analyzed the results, including the abstract and body of the article, figures, and tables. M.A.I.-E., I.A.A.-B., N.S.-H. and N.M.-F. helped with the statistical analysis and interpretation of the results. M.A.I.-E., R.B.-M. and N.M.-F. helped with the writing of the original draft. O.H.A.-M., S.L.-V. and M.A.I.-E. helped with the review and editing of the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This study was not supported by any funding.

Institutional Review Borad Statement

This article does not contain studies with human participants or animals performed by any author.

Data Availability Statement

The database is under the protection of the corresponding author. Therefore, if you would like to obtain this database, please contact Mario Alberto Isiordia-Espinoza.

Acknowledgments

Not applicable.

Conflicts of Interest

The authors declare no competing interests.

References

  1. Chakraborty, P.K.; Shai, A.; Tilak, P.B.D.; Kumar, A.; Kamdar, A.; Niranjana, A.; Kisave, P.N. Comparative Analgesic Efficacy of Intramuscular Dexamethasone, Ketorolac, Tramadol, and Butorphanol with Regard to Postoperative Pain After Mandibular Third Molar Surgery. J. Pharm. Bioallied Sci. 2024, 16 (Suppl. S2), S1378–S1380. [Google Scholar] [CrossRef]
  2. Latifi, F.; Choobsaz, P.; Yousefi-Koma, A.A.; Yousefi-Koma, H.; Mirtaleb, M.H. Comparison of the analgesic effects of single-dose 75 mg oral pregabalin versus single-dose 400 mg oral ibuprofen after impacted third mandibular molar surgery: A randomized, double-blind, split-mouth clinical trial. Dent. Med. Probl. 2023, 60, 619–625. [Google Scholar] [CrossRef]
  3. Palaia, G.; Tenore, G.; Tribolati, L.; Russo, C.; Gaimari, G.; Del Vecchio, A.; Romeo, U. Evaluation of wound healing and postoperative pain after oral mucosa laser biopsy with the aid of compound with chlorhexidine and sodium hyaluronate: A randomized double blind clinical trial. Clin. Oral Investig. 2019, 23, 3141–3151. [Google Scholar] [CrossRef] [PubMed]
  4. Pippi, R. Post-Surgical Clinical Monitoring of Soft Tissue Wound Healing in Periodontal Implant Surgery. Int. J. Med. Sci. 2017, 14, 721–728. [Google Scholar] [CrossRef] [PubMed]
  5. Patil, S.K.R.; Bhola, N. Efficacy of Kinesio taping in post operative sequalae after surgical removal of mandibular third molars: A split mouth randomized control study. BMC Oral Health 2023, 23, 964. [Google Scholar] [CrossRef] [PubMed]
  6. Thuruthel, M.J.; Surej Kumar, L.K.; Kurien, N.M.; Tharakan, M. Efficacy of gelatamp in controlling the postoperative sequelae following mandibular posterior teeth extraction—Asplit-mouth study. J. Oral Biol. Craniofacial Res. 2023, 13, 96–103. [Google Scholar] [CrossRef]
  7. Gursoytrak, B.; Kocaturk, Ö.; Koparal, M.; Gulsun, B. Comparison of Dexmedetomidine Ketamine for Managing Postoperative Symptoms After Third-Molar Surgery. J. Oral Maxillofac. Surg. 2021, 79, 532–536. [Google Scholar] [CrossRef]
  8. Patil, C.; Jadhav, A.K.R.; Bhola, N.; Borle, R.M.; Mishra, A. Piezosurgery vs bur in impacted mandibular third molar surgery: Evaluation of postoperative sequelae. J. Oral Biol. Craniofacial Res. 2019, 9, 259–262. [Google Scholar] [CrossRef]
  9. Aloy-Prósper, A.; Pellicer-Chover, H.; Balaguer-Martínez, J.; Llamas-Monteagudo, O.; Peñarrocha-Diago, M. Patient compliance to postoperative instructions after third molar surgery comparing traditional verbally written form versus the effect of a postoperative phone call follow-up a: Arandomized clinical study. J. Clin. Exp. Dent. 2020, 12, e909–e915. [Google Scholar] [CrossRef]
  10. Shenoi, R.S.; Rajguru, J.G.; Parate, S.R.; Ingole, P.D.; Khandaitkar, S.R.; Karmarkar, J.S. Compliance of postoperative instructions following the surgical extraction of impacted lower third molars Indian. J. Dent. Res. Off. Publ. Indian Soc. Dent. Res. 2021, 32, 87–91. [Google Scholar] [CrossRef]
  11. Alvira-González, J.; Gay-Escoda, C. Compliance of postoperative instructions following the surgical extraction of impacted lower third molars: A randomized clinical trial. Med. Oral Patol. Oral Cir. Bucal 2015, 20, e224–e230. [Google Scholar] [CrossRef]
  12. Camps-Font, O.; Sábado-Bundó, H.; Toledano-Serrabona, J.; Valmaseda-de-la-Rosa, N.; Figueiredo, R.; Valmaseda-Castellón, E. Antibiotic prophylaxis in the prevention of dry socket surgical site infection after lower third molar extraction: A network meta-analysis. Int. J. Oral Maxillofac. Surg. 2024, 53, 57–67. [Google Scholar] [CrossRef] [PubMed]
  13. Torof, E.; Morrissey, H.; Ball, P.A. The Role of Antibiotic Use in Third Molar Tooth Extractions: A Systematic Review and Meta-Analysis. Medicina 2023, 59, 422. [Google Scholar] [CrossRef] [PubMed]
  14. Varvara, G.; Bernardi, S.; Cutilli, T.; Bianchi, S.; Sinjari, B.; Piattelli, M. Anti-inflammatory steroid use in impacted third molar surgery: A systematic review. J. Biol. Regul. Homeost. Agents 2017, 31, 1095–1099. [Google Scholar] [PubMed]
  15. Pergolizzi, J.V.; Breve, F.; Magnusson, P.; LeQuang, J.K.; Varassi, G. Current and emerging COX inhibitors for treating postoperative pain following oral surgery. Expert Opin. Pharmacother. 2023, 24, 347–358. [Google Scholar] [CrossRef]
  16. Silva, P.U.J.; Meneses-Santos, D.; Vieira, W.A.; Ramacciato, J.C.; Silva, R.P.D.; Silva, M.C.P.D.; Rode, S.M.; Paranhos, L.R. Preemptive use of intravenous ibuprofen to reduce postoperative pain after lower third molar surgery: A systematic review of randomized controlled trials. Clinics 2021, 76, e2780. [Google Scholar] [CrossRef]
  17. Cetira Filho, E.L.; Carvalho, F.S.R.; de Barros Silva, P.G.; Barbosa, D.A.F.; Alves Pereira, K.M.; Ribeiro, T.R.; Costa, F.W.G. Preemptive use of oral nonsteroidal anti-inflammatory drugs for the relief of inflammatory events after surgical removal of lower third molars: Asystematic review with meta-analysis of placebo-controlled randomized clinical trials. J. Cranio Maxillofac. Surg. 2020, 48, 293–307. [Google Scholar] [CrossRef]
  18. Gounari, M.M.; Tsaousi, G.; Zouloumis, L.; Kouvelas, D.; Pourzitaki, C. Efficacy and safety of parenteral and local application of tramadol in mandibular third molar extraction: A qualitative systematic review of current evidence. Oral Maxillofac. Surg. 2024, 28, 499–513. [Google Scholar] [CrossRef]
  19. Selvido, D.I.; Bhattarai, B.P.; Niyomtham, N.; Riddhabhaya, A.; Vongsawan, K.; Pairuchvej, V.; Wongsirichat, N. Review of dexamethasone administration for management of complications in postoperative third molar surgery. J. Korean Assoc. Oral Maxillofac. Surg. 2021, 47, 341–350. [Google Scholar] [CrossRef]
  20. Franco-de la Torre, L.; Figueroa-Fernández, N.P.; Franco-González, D.L.; Alonso-Castro, Á.J.; Rivera-Luna, F.; Isiordia-Espinoza, M.A.A. Meta-Analysis of the Analgesic Efficacy of Single-Doses of Ibuprofen Compared to Traditional Non-Opioid Analgesics Following Third Molar Surgery. Pharmaceuticals 2021, 14, 360. [Google Scholar] [CrossRef]
  21. Klinger, R.; Stuhlreyer, J.; Schwartz, M.; Schmitz, J.; Colloca, L. Clinical Use of Placebo Effects in Patients With Pain Disorders. Int. Rev. Neurobiol. 2018, 139, 107–128. [Google Scholar] [CrossRef]
  22. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  23. Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; Moher, D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. Ann. Intern. Med. 2009, 151, W65–W94. [Google Scholar] [CrossRef] [PubMed]
  24. Higgins, J.P.; Green, S. (Eds.) Cochrane Handbook for Systematic Reviews of Interventions; Version 5.1.0; The Cochrane Collaboration: Oxford, UK, 2011; Available online: http://www.cochranehandbook.org (accessed on 9 September 2024).
  25. Leonardo, R. PICO: Model for clinical questions. Evid.-Based Med. Pract. 2018, 3, 2. [Google Scholar]
  26. Higgins, J.P.; Altman, D.G.; Gøtzsche, P.C.; Jüni, P.; Moher, D.; Oxman, A.D.; Savovic, J.; Schulz, K.F.; Weeks, L.; Sterne, J.A.; et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011, 343, d5928. [Google Scholar] [CrossRef] [PubMed]
  27. Sung, J.M.; Kim, J.Y.; Kwon, B.S.; Kim, K.N. Risk of bias for randomized controlled trials in Journal of Clinical Monitoring Computing. J. Clin. Monit. Comput. 2023, 37, 103–111. [Google Scholar] [CrossRef]
  28. Isiordia-Espinoza, M.A.; Franco-González, M.A.; Alonso-Castro, Á.J.; Franco-de la Torre, L. Analgesic effectiveness safety of celecoxib versus non-opioid active controls after third molar surgery: Ameta-analytical evaluation. J. Stomatol. Oral Maxillofac. Surg. 2022, 123, e1–e9. [Google Scholar] [CrossRef]
  29. Isiordia-Espinoza, M.A.; Alonso-Castro, Á.J.; Serafín-Higuera, N.; Castañeda-Santana, D.I.; de la Rosa Coronado, M.; Bologna-Molina, R.E. Postoperative administration of ketorolac compared to other drugs for pain control after third molar surgery: Ameta-analysis of double-blind randomized clinical trials. Br. J. Clin. Pharmacol. 2022, 88, 2591–2604. [Google Scholar] [CrossRef]
  30. Jones, A.; Steel, D. Evaluating the quality of medical evidence in real-world contexts. J. Eval. Clin. Pract. 2018, 24, 950–956. [Google Scholar] [CrossRef]
  31. Atkins, D.; Eccles, M.; Flottorp, S.; Guyatt, G.H.; Henry, D.; Hill, S.; Liberati, A.; O’Connell, D.; Oxman, A.D.; Phillips, B.; et al. Systems for grading the quality of evidence and the strength of recommendations I: Critical appraisal of existing approaches The GRADE Working Group. BMC Health Serv. Res. 2004, 4, 38. [Google Scholar] [CrossRef]
  32. Guyatt, G.H.; Oxman, A.D.; Vist, G.E.; Kunz, R.; Falck-Ytter, Y.; Alonso-Coello, P.; Schünemann, H.J. GRADE Working Group GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008, 336, 924–926. [Google Scholar] [CrossRef] [PubMed]
  33. Higgins, J.P.; Thompson, S.G.; Deeks, J.J.; Altman, D.G. Measuring inconsistency in meta-analyses. BMJ 2003, 327, 557–560. [Google Scholar] [CrossRef] [PubMed]
  34. Whitley, E.; Ball, J. Statistics review 3: Hypothesis testing and P values. Crit. Care 2002, 6, 222–225. [Google Scholar] [CrossRef] [PubMed]
  35. Citrome, L.; Ketter, T.A. When does a difference make a difference? Interpretation of number needed to treat number needed to harm likelihood to be helped or harmed. Int. J. Clin. Pract. 2013, 67, 407–411. [Google Scholar] [CrossRef]
  36. Andrade, C. The numbers needed to treat harm, (NNT; NNH) statistics: What they tell us what they do not. J. Clin. Psychiatry 2015, 76, e330–e333. [Google Scholar] [CrossRef]
  37. Risk Reduction Calculator. Available online: http://araw.mede.uic.edu/cgi-bin/nntcalc.pl (accessed on 24 October 2024).
  38. Ahlström, U.; Bakshi, R.; Nilsson, P.; Wåhlander, L. The analgesic efficacy of diclofenac dispersible ibuprofen in postoperative pain after dental extraction. Eur. J. Clin. Pharmacol. 1993, 44, 587–588. [Google Scholar] [CrossRef]
  39. Bakshi, R.; Frenkel, G.; Dietlein, G.; Meurer-Witt, B.; Schneider, B.; Sinterhauf, U. A placebo-controlled comparative evaluation of diclofenac dispersible versus ibuprofen in postoperative pain after third molar surgery. J. Clin. Pharmacol. 1994, 34, 225–230. [Google Scholar] [CrossRef]
  40. Black, P.; Max, M.B.; Desjardins, P.; Norwood, T.; Ardia, A.; Pallotta, T. A randomized double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain. Clin. Ther. 2002, 24, 1072–1089. [Google Scholar] [CrossRef]
  41. Brain, P.; Leyva, R.; Doyle, G.; Kellstein, D. Onset of analgesia efficacy of ibuprofen sodium in postsurgical dental pain: A randomized placebo-controlled study versus standard ibuprofen. Clin. J. Pain 2015, 31, 444–450. [Google Scholar] [CrossRef]
  42. Brown, J.D.; Daniels, S.E.; Bandy, D.P.; Ko, A.T.; Gammaitoni, A.; Mehta, A.; Boice, J.A.; Losada, M.C.; Peloso, P.M. Evaluation of multiday analgesia with etoricoxib in a double-blind randomized controlled trial using the postoperative third-molar extraction dental pain model. Clin. J. Pain 2013, 29, 492–498. [Google Scholar] [CrossRef]
  43. Cheung, R.; Krishnaswami, S.; Kowalski, K. Analgesic efficacy of celecoxib in postoperative oral surgery pain: A single-dose, two-center, randomized, double-blind, active- and placebo-controlled study. Clin. Ther. 2007, 29, 2498–2510. [Google Scholar] [CrossRef]
  44. Chopra, D.; Rehan, H.S.; Mehra, P.; Kakkar, A.K. A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model. Int. J. Oral Maxillofac. Surg. 2009, 38, 350–355. [Google Scholar] [CrossRef] [PubMed]
  45. Christensen, S.; Paluch, E.; Jayawardena, S.; Daniels, S.; Meeves, S. Analgesic Efficacy of a New Immediate-Release/Extended-Release Formulation of Ibuprofen: Results From Single- and Multiple-Dose Postsurgical Dental Pain Studies. Clin. Pharmacol. Drug Dev. 2017, 6, 302–312. [Google Scholar] [CrossRef] [PubMed]
  46. Cooper, S.A.; Cowan, A.; Tallarida, R.J.; Hargreaves, K.; Roszkowski, M.; Jamali, F.; Borenstein, M.; Lucyk, D.; Fielding, A.F.; Smith, B.; et al. The Analgesic Interaction of Misoprostol with Nonsteroidal Anti-Inflammatory Drugs. Am. J. Ther. 1996, 3, 261–267. [Google Scholar] [CrossRef] [PubMed]
  47. Cooper, S.A.; Desjardins, P.; Brain, P.; Paredes-Diaz, A.; Troullos, E.; Centofanti, R.; An, B. Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: A randomized, double-blind, placebo-controlled, single-dose trial. Curr. Med. Res. Opin. 2019, 35, 2149–2158. [Google Scholar] [CrossRef]
  48. Daniels, S.E.; Bandy, D.P.; Christensen, S.E.; Boice, J.; Losada, M.C.; Liu, H.; Mehta, A.; Peloso, P.M. Evaluation of the dose range of etoricoxib in an acute pain setting using the postoperative dental pain model. Clin. J. Pain 2011, 27, 1–8. [Google Scholar] [CrossRef]
  49. Daniels, S.E.; Atkinson, H.C.; Stanescu, I.; Frampton, C. Analgesic Efficacy of an Acetaminophen/Ibuprofen Fixed-dose Combination in Moderate to Severe Postoperative Dental Pain: A Randomized, Double-blind, Parallel-group, Placebo-controlled Trial. Clin. Ther. 2018, 40, 1765–1776.e5. [Google Scholar] [CrossRef]
  50. Desjardins, P.; Black, P.; Papageorge, M.; Norwood, T.; Shen, D.D.; Norris, L.; Ardia, A. Ibuprofen arginate provides effective relief from postoperative dental pain with a more rapid onset of action than ibuprofen. Eur. J. Clin. Pharmacol. 2002, 58, 387–394. [Google Scholar] [CrossRef]
  51. Dionne, R.A.; McCullagh, L. Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of ibuprofen. Clin. Pharmacol. Ther. 1998, 63, 694–701. [Google Scholar] [CrossRef]
  52. Ehrich, E.W.; Dallob, A.; De Lepeleire, I.; Van Hecken, A.; Riendeau, D.; Yuan, W.; Porras, A.; Wittreich, J.; Seibold, J.R.; De Schepper, P.; et al. Characterization of rofecoxib as a cyclooxygenase-2 isoform inhibitor and demonstration of analgesia in the dental pain model. Clin. Pharmacol. Ther. 1999, 65, 336–347. [Google Scholar] [CrossRef]
  53. Forbes, J.A.; Beaver, W.T.; Jones, K.F.; Kehm, C.J.; Smith, W.K.; Gongloff, C.M.; Zeleznock, J.R.; Smith, J.W. Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain. Clin. Pharmacol. Ther. 1991, 49, 674–684. [Google Scholar] [CrossRef] [PubMed]
  54. Forbes, J.A.; Edquist, I.A.; Smith, F.G.; Schwartz, M.K.; Beaver, W.T. Evaluation of bromfenac, aspirin, and ibuprofen in postoperative oral surgery pain. Pharmacotherapy 1991, 11, 64–70. [Google Scholar] [CrossRef] [PubMed]
  55. Forbes, J.A.; Beaver, W.T.; Jones, K.F.; Edquist, I.A.; Gongloff, C.M.; Smith, W.K.; Smith, F.G.; Schwartz, M.K. Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain. Clin. Pharmacol. Ther. 1992, 51, 343–352. [Google Scholar] [CrossRef] [PubMed]
  56. Fricke, J.R.; Halladay, S.C.; Francisco, C.A. Efficacy and safety of naproxen sodium and ibuprofen for pain relief after oral surgery. Curr. Ther. Res. 1993, 54, 619–627. [Google Scholar] [CrossRef]
  57. Gay, C.; Planas, E.; Donado, M.; Martínez, J.M.; Artigas, R.; Torres, F.; Mauleón, D.; Carganico, G. Analgesic Efficacy of Low Doses of Dexketoprofen in the Dental Pain Model. Clin. Drug Investig. 1996, 11, 320–330. [Google Scholar] [CrossRef]
  58. Giles, A.D.; Hill, C.M.; Shepherd, J.P.; Stewart, D.J.; Pickvance, N.J. A single dose assessment of an ibuprofen/codeine combination in postoperative dental pain. Int. J. Oral Maxillofac. Surg. 1986, 15, 727–732. [Google Scholar] [CrossRef]
  59. Hersh, E.V.; Cooper, S.; Betts, N.; Wedell, D.; MacAfee, K.; Quinn, P.; Lamp, C.; Gaston, G.; Bergman, S.; Henry, E. Single dose and multidose analgesic study of ibuprofen and meclofenamate sodium after third molar surgery. Oral Surg. Oral Med. Oral Pathol. 1993, 76, 680–687. [Google Scholar] [CrossRef]
  60. Hersh, E.V.; Levin, L.M.; Cooper, S.A.; Doyle, G.; Waksman, J.; Wedell, D.; Hong, D.; Secreto, S.A. Ibuprofen liquigel for oral surgery pain. Clin. Ther. 2000, 22, 1306–1318. [Google Scholar] [CrossRef]
  61. Hill, C.M.; Balkenohl, M.; Thomas, D.W.; Walker, R.; Mathé, H.; Murray, G. Pregabalin in patients with postoperative dental pain. Eur. J. Pain 2001, 5, 119–124. [Google Scholar] [CrossRef]
  62. Isola, G.; Matarese, M.; Ramaglia, L.; Iorio-Siciliano, V.; Cordasco, G.; Matarese, G. Efficacy of a drug composed of herbal extracts on postoperative discomfort after surgical removal of impacted mandibular third molar: A randomized, triple-blind, controlled clinical trial. Clin. Oral Investig. 2019, 23, 2443–2453. [Google Scholar] [CrossRef]
  63. Isola, G.; Matarese, M.; Ramaglia, L.; Cicciù, M.; Matarese, G. Evaluation of the efficacy of celecoxib ibuprofen on postoperative pain swelling mouth opening after surgical removal of impacted third molars: A randomized controlled clinical trial. Int. J. Oral Maxillofac. Surg. 2019, 48, 1348–1354. [Google Scholar] [CrossRef] [PubMed]
  64. Jones, K.; Seymour, R.A.; Hawkesford, J.E. Are the pharmacokinetics of ibuprofen important determinants for the drug’s efficacy in postoperative pain after third molar surgery? Br. J. Oral Maxillofac. Surg. 1997, 35, 173–176. [Google Scholar] [CrossRef] [PubMed]
  65. Joshi, A.; Parara, E.; Macfarlane, T.V. A double-blind randomised controlled clinical trial of the effect of preoperative ibuprofen, diclofenac, paracetamol with codeine and placebo tablets for relief of postoperative pain after removal of impacted third molars. Br. J. Oral Maxillofac. Surg. 2004, 42, 299–306. [Google Scholar] [CrossRef] [PubMed]
  66. Kellstein, D.; Leyva, R. Evaluation of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: A Pilot, Dose-Ranging, Randomized Study. Drugs RD 2020, 20, 237–247. [Google Scholar] [CrossRef]
  67. Kiersch, T.A.; Halladay, S.C.; Koschik, M. A double-blind, randomized study of naproxen sodium, ibuprofen, and placebo in postoperative dental pain. Clin. Ther. 1993, 15, 845–854. [Google Scholar]
  68. La Monaca, G.; Pranno, N.; Annibali, S.; Polimeni, A.; Pompa, G.; Vozza, I.; Cristalli, M.P. Comparative analgesic effects of single-dose preoperative administration of paracetamol (acetaminophen) 500 mg plus codeine 30 mg ibuprofen 400 mg on pain after third molar surgery. J. Evid. Based Dent. Pract. 2021, 21, 101611. [Google Scholar] [CrossRef]
  69. Lyngstad, G.; Skjelbred, P.; Swanson, D.M.; Skoglund, L.A. Analgesic effect of oral ibuprofen 400, 600, and 800 mg; paracetamol 500 and 1000 mg; and paracetamol 1000 mg plus 60 mg codeine in acute postoperative pain: A single-dose, randomized, placebo-controlled, and double-blind study. Eur. J. Clin. Pharmacol. 2021, 77, 1843–1852. [Google Scholar] [CrossRef]
  70. Malmstrom, K.; Daniels, S.; Kotey, P.; Seidenberg, B.C.; Desjardins, P.J. Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: A randomized, placebo- and active-comparator-controlled clinical trial. Clin. Ther. 1999, 21, 1653–1663. [Google Scholar] [CrossRef]
  71. Malmstrom, K.; Fricke, J.R.; Kotey, P.; Kress, B.; Morrison, B. A comparison of rofecoxib versus celecoxib in treating pain after dental surgery: A single-center, randomized, double-blind, placebo- and active-comparator-controlled, parallel-group, single-dose study using the dental impaction pain model. Clin. Ther. 2002, 24, 1549–1560. [Google Scholar] [CrossRef]
  72. Malmstrom, K.; Sapre, A.; Couglin, H.; Agrawal, N.G.; Mazenko, R.S.; Fricke, J.R., Jr. Etoricoxib in acute pain associated with dental surgery: A randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. Clin. Ther. 2004, 26, 667–679. [Google Scholar] [CrossRef]
  73. McQuay, H.J.; Angell, K.; Carroll, D.; Moore, R.A.; Juniper, R.P. Ibuprofen compared with ibuprofen plus caffeine after third molar surgery. Pain 1996, 66, 247–251. [Google Scholar] [CrossRef]
  74. Medve, R.A.; Wang, J.; Karim, R. Tramadol and acetaminophen tablets for dental pain. Anesth. Prog. 2001, 48, 79–81. [Google Scholar]
  75. Mehlisch, D.R.; Ardia, A.; Pallotta, T. A controlled comparative study of ibuprofen arginate versus conventional ibuprofen in the treatment of postoperative dental pain. J. Clin. Pharmacol. 2002, 42, 904–911. [Google Scholar] [CrossRef] [PubMed]
  76. Mehlisch, D.R.; Aspley, S.; Daniels, S.E.; Bandy, D.P. Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol alone in the management of moderate to severe acute postoperative dental pain in adolescents and adults: A randomized, double-blind, placebo-controlled, parallel-group, single-dose, two-center, modified factorial study. Clin. Ther. 2010, 32, 882–895. [Google Scholar] [CrossRef] [PubMed]
  77. Mehlisch, D.R.; Aspley, S.; Daniels, S.E.; Southerden, K.A.; Christensen, K.S. A single-tablet fixed-dose combination of racemic ibuprofen/paracetamol in the management of moderate to severe postoperative dental pain in adult and adolescent patients: A multicenter, two-stage, randomized, double-blind, parallel-group, placebo-controlled, factorial study. Clin. Ther. 2010, 32, 1033–1049. [Google Scholar] [CrossRef]
  78. Morrison, B.W.; Fricke, J.; Brown, J.; Yuan, W.; Kotey, P.; Mehlisch, D. The optimal analgesic dose of rofecoxib: Overview of six randomized controlled trials. J. Am. Dent. Assoc. 1939, 131, 1729–1737. [Google Scholar] [CrossRef]
  79. Nørholt, S.E.; Aagaard, E.; Svensson, P.; Sindet-Pedersen, S. Evaluation of trismus bite force pressure algometry after third molar surgery: A placebo-controlled study of ibuprofen. J. Oral Maxillofac. Surg. 1998, 56, 420–429. [Google Scholar] [CrossRef]
  80. Olson, N.Z.; Otero, A.M.; Marrero, I.; Tirado, S.; Cooper, S.; Doyle, G.; Jayawardena, S.; Sunshine, A. Onset of analgesia for liquigel ibuprofen 400 mg acetaminophen 1000 mg ketoprofen 25 mg placebo in the treatment of postoperative dental pain. J. Clin. Pharmacol. 2001, 41, 1238–1247. [Google Scholar] [CrossRef]
  81. Ostenfeld, T.; Price, J.; Albanese, M.; Bullman, J.; Guillard, F.; Meyer, I.; Leeson, R.; Costantin, C.; Ziviani, L.; Nocini, P.F.; et al. A randomized controlled study to investigate the analgesic efficacy of single doses of the cannabinoid receptor-2 agonist, G.W.8.4.2.1.6.6.; ibuprofen or placebo in patients with acute pain following third molar tooth extraction. Clin. J. Pain 2011, 27, 668–676. [Google Scholar] [CrossRef]
  82. Planas, M.E.; Gay-Escoda, C.; Bagán, J.V.; Santamaría, J.; Peñarrocha, M.; Donado, M.; Puerta, J.L.; García-Magaz, I.; Ruíz, J.; Ortiz, P. Oral metamizol (1 g 2 g) versus ibuprofen placebo in the treatment of lower third molar surgery pain: Randomised double-blind multi-centre study Cooperative Study Group. Eur. J. Clin. Pharmacol. 1998, 53, 405–409. [Google Scholar] [CrossRef]
  83. Schou, S.; Nielsen, H.; Nattestad, A.; Hillerup, S.; Ritzau, M.; Branebjerg, P.E.; Bugge, C.; Skoglund, L.A. Analgesic dose-response relationship of ibuprofen 50, 100, 200, and 400 mg after surgical removal of third molars: A single-dose, randomized, placebo-controlled, and double-blind study of 304 patients. J. Clin. Pharmacol. 1998, 38, 447–454. [Google Scholar] [CrossRef] [PubMed]
  84. Schwartz, J.I.; Kotey, P.N.; Fricke, J.R., Jr.; Gottesdiener, K. MK-0703 (a Cyclooxygenase-2 inhibitor) in Acute Pain Associated with Dental Surgery: A Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Dose-Ranging Study. Am. J. Ther. 2007, 14, 13–19. [Google Scholar] [CrossRef] [PubMed]
  85. Seymour, R.A.; Hawkesford, J.E.; Weldon, M.; Brewster, D. An evaluation of different ibuprofen preparations in the control of postoperative pain after third molar surgery. Br. J. Clin. Pharmacol. 1991, 31, 83–87. [Google Scholar] [CrossRef] [PubMed]
  86. Seymour, R.A.; Ward-Booth, P.; Kelly, P.J. Evaluation of different doses of soluble ibuprofen ibuprofen tablets in postoperative dental pain. Br. J. Oral Maxillofac. Surg. 1996, 34, 110–114. [Google Scholar] [CrossRef]
  87. Seymour, R.A.; Frame, J.; Negus, T.W.; Hawkesford, J.E.; Marsden, J.; Matthew, I.R. The comparative efficacy of aceclofenac ibuprofen in postoperative pain after third molar surgery. Br. J. Oral Maxillofac. Surg. 1998, 36, 375–379. [Google Scholar] [CrossRef]
  88. Seymour, R.A.; Hawkesford, J.E.; Hill, C.M.; Frame, J.; Andrews, C. The efficacy of a novel adenosine agonist (WAG994) in postoperative dental pain. Br. J. Clin. Pharmacol. 1999, 47, 675–680. [Google Scholar] [CrossRef]
  89. Seymour, R.A.; Watkinson, H.; Hawkesford, J.E.; Moore, U. The efficacy of buffered ketoprofen in postoperative pain after third molar surgery. Eur. J. Clin. Pharmacol. 2000, 55, 801–806. [Google Scholar] [CrossRef]
  90. Sunshine, A.; Olson, N.Z.; Marrero, I.; Tirado, S. Onset duration of analgesia for low-dose ketoprofen in the treatment of postoperative dental pain. J. Clin. Pharmacol. 1998, 38, 1155–1164. [Google Scholar] [CrossRef]
  91. Troullos, E.S.; Hargreaves, K.M.; Butler, D.P.; Dionne, R.A. Comparison of nonsteroidal anti-inflammatory drugs ibuprofen flurbiprofen with methylprednisolone placebo for acute pain swelling trismus. J. Oral Maxillofac. Surg. 1990, 48, 945–952. [Google Scholar] [CrossRef]
  92. Van Dyke, T.; Litkowski, L.J.; Kiersch, T.A.; Zarringhalam, N.M.; Zheng, H.; Newman, K. Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of postoperative pain: A double-blind, placebo- and active-controlled parallel-group study. Clin. Ther. 2004, 26, 2003–2014. [Google Scholar] [CrossRef]
  93. Weiser, T.; Richter, E.; Hegewisch, A.; Muse, D.D.; Lange, R. Efficacy safety of a fixed-dose combination of ibuprofen caffeine in the management of moderate to severe dental pain after third molar extraction. Eur. J. Pain 2018, 22, 28–38. [Google Scholar] [CrossRef]
  94. Zelenakas, K.; Fricke, J.R., Jr.; Jayawardene, S.; Kellstein, D. Analgesic efficacy of single oral doses of lumiracoxib ibuprofen in patients with postoperative dental pain. Int. J. Clin. Pract. 2004, 58, 251–256. [Google Scholar] [CrossRef]
  95. Moore, R.A.; Derry, S.; Wiffen, P.J.; Banerjee, S.; Karan, R.; Glimm, E.; Wiksten, A.; Aldington, D.; Eccleston, C. Estimating relative efficacy in acute postoperative pain: Network meta-analysis is consistent with indirect comparison to placebo alone. Pain 2018, 159, 2234–2244. [Google Scholar] [CrossRef] [PubMed]
  96. Moore, A.R.; Straube, S.; Paine, J.; Derry, S.; McQuay, H.J. Minimum efficacy criteria for comparisons between treatments using individual patient meta-analysis of acute pain trials: Examples of etoricoxib, paracetamol, ibuprofen, and ibuprofen/paracetamol combinations after third molar extraction. Pain 2011, 152, 982–989. [Google Scholar] [CrossRef] [PubMed]
  97. Bushra, R.; Aslam, N. An overview of clinical pharmacology of Ibuprofen. Oman Med. J. 2010, 25, 155–1661. [Google Scholar] [CrossRef] [PubMed]
  98. Rocca, G.D.; Chiarandini, P.; Pietropaoli, P. Analgesia in PACU: Nonsteroidal anti-inflammatory drugs. Curr. Drug Targets 2005, 6, 781–787. [Google Scholar] [CrossRef]
  99. Halpern, S.M.; Fitzpatrick, R.; Volans, G.N. Ibuprofen toxicity. A review of adverse reactions and overdose. Advers. Drug React. Toxicol. Rev. 1993, 12, 107–128. [Google Scholar]
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Figure 1. Study flow chart.
Figure 1. Study flow chart.
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Figure 2. Bias risk assessment [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94].
Figure 2. Bias risk assessment [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94].
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Figure 3. Number of patients who took rescue analgesics [38,39,41,42,43,44,45,47,48,49,53,57,59,60,62,64,65,68,69,70,71,72,76,77,79,82,84,85,86,87,88,89,93,94].
Figure 3. Number of patients who took rescue analgesics [38,39,41,42,43,44,45,47,48,49,53,57,59,60,62,64,65,68,69,70,71,72,76,77,79,82,84,85,86,87,88,89,93,94].
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Figure 4. Global evaluation of study medications [39,41,42,47,49,57,59,60,66,69,70,71,72,76,77,80,84,85,86,87,88,89,94].
Figure 4. Global evaluation of study medications [39,41,42,47,49,57,59,60,66,69,70,71,72,76,77,80,84,85,86,87,88,89,94].
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Figure 5. Adverse effects of ibuprofen 200 mg and placebo [40,46,49,51,53,59,60,73,75,77,83,89,90].
Figure 5. Adverse effects of ibuprofen 200 mg and placebo [40,46,49,51,53,59,60,73,75,77,83,89,90].
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Figure 6. Adverse effects of ibuprofen 400 mg and placebo [39,40,41,43,47,51,54,55,57,59,60,66,70,71,72,73,74,75,76,77,80,81,83,84,85,87,92,93].
Figure 6. Adverse effects of ibuprofen 400 mg and placebo [39,40,41,43,47,51,54,55,57,59,60,66,70,71,72,73,74,75,76,77,80,81,83,84,85,87,92,93].
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Figure 7. Adverse effects of ibuprofen 600 mg and placebo [42,45,48,82].
Figure 7. Adverse effects of ibuprofen 600 mg and placebo [42,45,48,82].
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Figure 8. Publication risk assessment using the variables analgesic consumption (a) [38,39,41,42,43,44,45,47,48,49,53,57,59,60,62,64,65,68,69,70,71,72,76,77,79,82,84,85,86,87,88,89,93,94] and overall evaluation of treatments (b) [39,41,42,47,49,57,59,60,66,69,70,71,72,76,77,80,84,85,86,87,88,89,94].
Figure 8. Publication risk assessment using the variables analgesic consumption (a) [38,39,41,42,43,44,45,47,48,49,53,57,59,60,62,64,65,68,69,70,71,72,76,77,79,82,84,85,86,87,88,89,93,94] and overall evaluation of treatments (b) [39,41,42,47,49,57,59,60,66,69,70,71,72,76,77,80,84,85,86,87,88,89,94].
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Table 1. The number needed to treat (NNT), the number needed to harm (NNH), and the confidence intervals (CIs) of ibuprofen for pain control after third molar surgery.
Table 1. The number needed to treat (NNT), the number needed to harm (NNH), and the confidence intervals (CIs) of ibuprofen for pain control after third molar surgery.
Analgesic EfficacyIbuprofen
200 mg400 mg600 mg
nNNTCIsnNNTCIsnNNTCIs
The number of patients who took rescue analgesics7973.73 to 4.728033.12.8 to 3.411493.42.8 to 4.2
Overall evaluation6942.62.2 to 3.124071.91.8 to 22911.61.4 to 2
Adverse effectsnNNHCIsnNNHCIsnNNHCIs
Nausea146127.616.3 to 89.8391728.418.4 to 61.6---
Vomiting131942.622.3 to 477.7312429.619 to 66.37161710 to 50.8
Headache134224.814.8 to 76.9247726.717.2 to 59.371612.37.7 to 31.2
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MDPI and ACS Style

Mora-Falcón, I.J.; Amador-Beas, I.A.; Bologna-Molina, R.; Molina-Frechero, N.; Aragón-Martínez, O.H.; Serafín-Higuera, N.; López-Verdín, S.; Isiordia-Espinoza, M.A. Analgesic Efficacy of Postoperative Ibuprofen in Third Molar Surgery: A Meta-Analysis. Oral 2025, 5, 72. https://doi.org/10.3390/oral5030072

AMA Style

Mora-Falcón IJ, Amador-Beas IA, Bologna-Molina R, Molina-Frechero N, Aragón-Martínez OH, Serafín-Higuera N, López-Verdín S, Isiordia-Espinoza MA. Analgesic Efficacy of Postoperative Ibuprofen in Third Molar Surgery: A Meta-Analysis. Oral. 2025; 5(3):72. https://doi.org/10.3390/oral5030072

Chicago/Turabian Style

Mora-Falcón, Itzel Joselyn, Iván Agustín Amador-Beas, Ronell Bologna-Molina, Nelly Molina-Frechero, Othoniel Hugo Aragón-Martínez, Nicolás Serafín-Higuera, Sandra López-Verdín, and Mario Alberto Isiordia-Espinoza. 2025. "Analgesic Efficacy of Postoperative Ibuprofen in Third Molar Surgery: A Meta-Analysis" Oral 5, no. 3: 72. https://doi.org/10.3390/oral5030072

APA Style

Mora-Falcón, I. J., Amador-Beas, I. A., Bologna-Molina, R., Molina-Frechero, N., Aragón-Martínez, O. H., Serafín-Higuera, N., López-Verdín, S., & Isiordia-Espinoza, M. A. (2025). Analgesic Efficacy of Postoperative Ibuprofen in Third Molar Surgery: A Meta-Analysis. Oral, 5(3), 72. https://doi.org/10.3390/oral5030072

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