Review A Meta-Analysis of the Analgesic Efficacy of Single-Doses of Ibuprofen Compared to Traditional Non-Opioid Analgesics Following Third Molar Surgery Lorenzo Franco-de la Torre 1, Norma Patricia Figueroa-Fernández 2, Diana Laura Franco-González 1, Ángel Josabad Alonso-Castro 3, Federico Rivera-Luna 2 and Mario Alberto Isiordia-Espinoza 1,* 1 Instituto de Investigación en Ciencias Médicas, Departamento de Clínicas, División de Ciencias Biomédicas, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, 47620, Mexico; [email protected] (L.F.-d.T.); [email protected] (D.L.F.-G.) 2 Departamento de Cirugía Oral y Maxilofacial, Facultad de Odontología, Universidad Autónoma de Baja California, Campus Mexicali, 21040, Mexico; [email protected] (N.P.F.-F.); [email protected] (F.R.-L.) 3 Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, 36250, Mexico; [email protected] * Correspondence: [email protected]; Tel.: 52-378-119-5786. Table S1. Features summary of the high-quality studies. Patients, evaluation period, First author, study design Evaluation of the clinical Treatments (n) and number of molars Adverse effects Conclusion and, and analgesic strategy efficacy extracted Ahlström et al., 1993 Group A: Ibuprofen 400 mg (n=32). Healthy patients. Pain was evaluated by VAS Diclofenac presented a Ibuprofen and diclofenac Randomized, double-blind, Group B: Diclofenac 50 mg (n=35). Assessment period was 6 h. at 20 and 40 minutes as well high incidence of adverse produced similar pain relief- parallel, clinical trial. Group C: Placebo (n=30). A mandibular third molar as 1 to 6 post-surgical h. effects when compared to analgesia. Single-dose study. All treatments were administered using the removed. ibuprofen and placebo Post-operative analgesia. oral route. Bakshi et al., 1994. Group A: Ibuprofen 400 mg (n=80). Healthy patients. Pain at 20 and 40 minutes, as Similar adverse effect were Diclofenac produced rapid Randomized, double-blind, Group B: Diclofenac 50 mg (n=83). Assessment period was 6 h. well as 1 to 6 post-surgical h observed for all treatments onset of analgesic effect in parallel, clinical trial. Group C: Placebo (n=82). One mandibular third molar with VAS, and VRS. Other comparison with ibuprofen Single-dose study. All treatments were administered using the extracted. variables were TOTPAR-6, and placebo. Post-operative analgesia. oral route. and global evaluation of treatments. Christensen et al., 2017. Group A: Ibuprofen 600 mg (n=109). Good health patients. Pain relief, PID, SPID, time Eleven patients receiving Ibuprofen presented faster Randomized, double-blind, Group B: Naproxen sodium 220 mg (n=58). The evaluation period was 24 to confirmed first ibuprofen and six patients onset and superior analgesia parallel, clinical trial. Group C: Placebo (n=29). h. perceptible relief, time to taking naproxen sodium than naproxen sodium. Single- and multi-dose study. (Clinical study 1). A third molar surgery. meaningful pain relief, time had adverse effects. Post-operative analgesia. to treatment failure, and percentage of treatment failures. Forbes et al., 1991. Group A: Ibuprofen 400 mg (n=37). Patients without clinical PID-4, PID-8, SPID-4, SPID- Similar number of adverse Bromfenac 25 mg and Randomized, double-blind, Group B. Aspirin 650 mg (n=41). significand condition. 8, peak PID score 4 and 8 h, effects were observed in all ibuprofen 400 mg were parallel, clinical trial. Group C: Bromfenac 5 mg (n=39). One to four third molar pain relief, TOTPAR-4, groups. significantly superior to the Single-dose study. Group D: Bromfenac 10 mg (n=43). extractions. TOTPAR-8 peak pain relief, other active treatments. Post-operative analgesia. Group E: Bromfenac 25 mg (n=42). Patients were evaluated total hours of 50% relief, and Group F: Placebo (n=39). during 8 h after surgery. overall evaluation. Forbes et al., 1992. Group A: Ibuprofen 400 mg (n=38). Patients without clinical PID, SPID, peak PID score, Similar frequency of Bromfenac 100 mg was more Randomized, double-blind, Group B. Aspirin 650 mg (n=38). significand condition. pain relief, TOTPAR-8, peak adverse effects were effective than ibuprofen. parallel, clinical trial. Group C: Bromfenac 10 mg (n=43). One to four third molar pain relief, total hours of observed in all groups. Single-dose study. Group D: Bromfenac 25 mg (n=41). extractions. 50% relief, and overall Post-operative analgesia. Group E: Bromfenac 50 mg (n=42). Patients were evaluated evaluation. Group F: Bromfenac 100 mg (n=40) during 8 h after surgery. Placebo (n=38). Hersh, et al., 1993. Group A: Ibuprofen 200 mg (n=51). Patients with good health. Pain intensity evaluation, Similar number of adverse The high dose of ibuprofen Randomized, double-blind, Group B: Ibuprofen 400 mg (n=49). One or more third molar PID, SPID, peak PID score, effects were recorded. and meclofenamate were parallel, clinical trial. Group C: Meclofenamate 50 (n=51). surgeries. pain relief, TOTPAR-8, peak most effective than the lower Single- and multi-dose study. Group D: Meclofenamate 100 (n=52). Patients were evaluated 8 h pain relief, overall doses of these agents after Post-operative analgesia. Group E: Placebo (n=51). following surgery. evaluation, and time to third molar surgery. remedication. Hersh, et al., 2000. Group A: Ibuprofen 200 mg. Patients with good health. TOTPAR-2, TOTPAR-6, All treatments were well Ibuprofen (200 and 400 mg) Randomized, double-blind, Group B: Ibuprofen 400 mg. One or more third molar SPID-2, SPID-6, onset of tolerated, with no serious was superior to parallel, clinical trial. Group C: Acetaminophen 1000 mg. surgeries. analgesia, and peak side effects reported. acetaminophen. Single- and multi-dose study. Group D: Placebo. Patients were evaluated 6 h analgesia effect, Post-operative analgesia. following surgery. remedication, and overall evaluation. Joshi et al., 2004. Group A: Ibuprofen 600 mg (n=31). Patients ASA I and II. Pain intensity was assessed There was no significant There was not difference Randomized, double-blind, Group B: Diclofenac 100 mg (n=29). A third molar extraction. using the VAS and VRS. difference among the between active treatments. parallel, clinical trial. Group C: Paracetamol 1000 mg and Codeine The evaluation period was 24 Time for the first analgesic groups. Single-dose study. 60 mg (n=30). h. and number of analgesic in Pre-operative analgesia. Group D: Placebo (n=29). the post-operative period were evaluated. Mehlisch et al., 2010a. Group A: Ibuprofen 400 mg (n=69). Healthy patients. SPIDR-4, SPRID-6, SPRID-8, Similar frequency of Ibuprofen/acetaminophen Randomized, double-blind, Group B: Acetaminophen 1000 mg (n=34). Two or more third molar TOTPAR-4, TOTPAR-6, adverse effects between all combination produced better parallel, clinical trial. Group C: Ibuprofen 400 mg/acetaminophen surgeries. TOTPAR-6, re-medication, treatments. analgesia than ibuprofen or Single-dose study. 1000 mg (n=67). Assessment period was 8 h. and global evaluation. acetaminophen alone. Post-operative analgesia. Group D: Ibuprofen 200 mg / acetaminophen 500 mg (n=33). Group E: Placebo (n=31). Mehlisch et al., 2010b. Group A: Ibuprofen 400 mg (n=74). Healthy patients. SPID-4, SPID-6, SPID-8, There was no significant Ibuprofen/acetaminophen Randomized, double-blind, Group B: Ibuprofen 200 mg (n=75). At least 3 lower third molar TOTPAR-4, TOTPAR-6, difference among the mixture was more effective parallel, clinical trial. Group C: Acetaminophen 1000 mg (n=74). surgeries. TOTPAR-6, re-medication, groups. than either drug alone. Single-dose study. Group D: Acetaminophen 500 mg (n=76). Assessment period was 8 h. and overall assessment of Post-operative analgesia. Group E: Ibuprofen 400 and acetaminophen study medication. 1000 mg (n=149). Group F: Ibuprofen 200 mg and acetaminophen 500 mg (n=143). Group G: Ibuprofen 100 mg and acetaminophen 250 mg (n=71). Group H: Placebo (n=73). Morrison et al., 2000. Group A: Ibuprofen 400 mg (n=127). Healthy patients and patients TOTPAR, onset of analgesia, Adverse effects of Rofecoxib provides analgesic Randomized, double-blind, Group B: Naproxen sodium 550 mg (n=140). with controlled systemic and peak analgesia effect, ibuprofen, naproxen efficacy similar a naproxen parallel, clinical trial. Group C: Placebo (n=275). disease. and overall evaluation. sodium, and placebo were sodium. Single-dose study. At least one mandibular third no shown. Post-operative analgesia. molar surgery. The evaluation was done through 24 hours. Olson et al., 2001. Group A: Ibuprofen 400 mg (n=67). Healthy patients. PRID, TOTPAR-2, TOTPAR- According to the Ibuprofen was superior to all Randomized, double-blind, Group B: Ketoprofen 25 mg (n=67). One or more third molar 6, SPID-2, SPID-6, SPRID-2, treatments, the adverse treatments. parallel, clinical trial. Group C: Acetaminophen 1000 mg (n=66). surgeries. SPRID-6, and the patient’s effects were next: Single-dose study. Group D: Placebo (n=39). Duration of trial was 6 hours overall evaluation of the 5.1% who received Post-operative analgesia. study medication. placebo. 7.5% in ketoprofen. 10.4% in ibuprofen 15.2% in acetaminophen. Planas et al., 1998. Group A: Ibuprofen 600 mg (n=74). Patients with sufficient mental Pain was evaluated using There was no difference Metamizol 2000 mg was Randomized, double-blind, Group B: Metamizol 1000 mg (n=75). status to complete the VAS and the verbal scale. between treatment groups. superior to ibuprofen and parallel, clinical trial. Group C: Metamizol 2000 mg (n=72). assessment PID and SPID were placebo for control of pain Single-dose study. Group D: Placebo (n=32). A third molar surgery. calculated. after surgery. Post-operative analgesia. Trial duration was 1 hour. Seymour et al., 1998. Group A: Ibuprofeno 400 mg (n=76). Healthy patients or patients AUC pain, AUC pain relief, There was no difference Ibuprofen was better Randomized, double-blind, Group B: Aceclofenac 150 mg (n=71).