Analgesic efficacy of diclofenac and ketoprofen patches versus ibuprofen tablets for pain control after archwire placement in orthodontic patients

Analgesic efficacy of diclofenac and ketoprofen patches versus ibuprofen tablets for pain control after archwire placement in orthodontic patients | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 28 April 2025 V1 Latest version Share on Analgesic efficacy of diclofenac and ketoprofen patches versus ibuprofen tablets for pain control after archwire placement in orthodontic patients Authors : Yasamin Babaee Hemmati and amirhossein toghrolian 0000-0002-4424-5785 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174582202.28212902/v1 746 views 324 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objectives: This study compared the analgesic efficacy of diclofenac and ketoprofen transdermal patches versus ibuprofen tablets for pain control following initial archwire placement in orthodontic patients. Materials and Methods: In this randomized clinical trial, 60 orthodontic patients were randomly assigned to 3 groups to receive either 30 mg ketoprofen transdermal patches every 12 hours, 15 mg diclofenac transdermal patches every 12 hours, or 400 mg ibuprofen tablets every 8 hours for 1 day. The pain severity was quantified at 2 and 6 hours, bedtime, 24 and 48 hours, and 3 and 7 days after initial archwire placement using the numeric rating scale (NRS). Data were analyzed by the generalized estimating equation (GEE), and the Kruskal Wallis, Bonferroni, Chi-square and Fisher’s exact tests (α=0.05). Results: The pain score was the lowest in the ketoprofen group, followed by the ibuprofen, and then the diclofenac group; but the difference was not significant (P>0.05). The pain score initially increased after archwire placement to 6 hours. It subsequently decreased until bedtime, increased again at 24 hours, and then followed a descending trend from 48 hours to 7 days. The trend of change in pain score over time was not significantly different among the three groups (P=0.657). Age (P=0.757) and gender (P=0.153) of patients did not affect their perceived pain. Conclusion: Considering the comparable analgesic efficacy of ibuprofen and the tested transdermal patches, diclofenac and ketoprofen patches may be used as an alternative to ibuprofen tablets for efficient pain control after initial archwire placement. Introduction Orthodontic treatment is performed to correct the position of misaligned teeth and create a beautiful smile using archwires, bonded brackets, aligners, or other orthodontic appliances for orthodontic tooth movement. However, this process can be associated with pain and discomfort for the patients. Understanding and management of this pain can facilitate the course of treatment for patients [1]. Pain is an unpleasant sensory experience associated with actual or possible tissue injury [2]. Pain control is highly important in orthodontic treatment since pain is the most common patient complaint and a major factor adversely affecting patient compliance [3]. The prevalence of orthodontic pain is relatively high, ranging from 77% to 95% [4]. Orthodontic pain is caused by the ischemia, inflammation, and edema of the compressed periodontal ligament. Inflammatory mediators such as histamine, bradykinin, prostaglandins, serotonin, and substance P are released in an inflamed periodontal ligament. These mediators stimulate the pain receptors, and generate pain as such [5]. Orthodontic pain often initiates within 2 hours following load application, reaches its peak during sleep or within 24 hours after appliance placement, and lasts for 5 to 7 days [6]. Orthodontic pain depends on factors such as age, gender, personal pain threshold, magnitude of the applied force, emotional state and stress level of patient, cultural issues, and previous pain experiences [7]. Different methods have been proposed for orthodontic pain control such as pharmacotherapy with non-steroidal anti-inflammatory drugs (NSAIDs), low-level laser therapy [5], transcutaneous electrical nerve stimulation [8], vibratory stimulation of the periodontal ligament, and bite wafers [6]. To date, using NSAIDs has been the most successful method of orthodontic pain control, and is considered as the gold standard for this purpose [6,9]. In brief, NSAIDs inhibit the cyclooxygenase (COX) enzymes and prevent the synthesis of arachidonic acid and subsequently the prostaglandins, which are important pain mediators [10]. Ibuprofen and diclofenac sodium are the most popular NSAIDs used for orthodontic pain control due to their optimal analgesic and anti-inflammatory properties [11]. Ketoprofen is another NSAID that not only inhibits the COX and lipoxygenase pathways, but also causes central and peripheral desensitization. Unlike other NSAIDs, ketoprofen inhibits central prostaglandin synthesis at both peripheral and central levels (brain COX and nitric oxide synthase), and is therefore expected to show high analgesic efficacy [12]. The half-life of ibuprofen is 1.8 to 2 hours while the half-life of diclofenac is 2 hours [13] and that of ketoprofen is 2-2.5 hours [14]. Close half-life of these medications enables more accurate comparison of their analgesic efficacy. Analgesics can be used through oral, injection, inhalation, and transdermal routes. Oral administration of a drug carries the potential for its first-pass metabolism and loss of a significant amount of the drug before it is absorbed systemically [15]. Moreover, oral intake of medications can be associated with a risk of gastrointestinal problems, renal insufficiency, hepatotoxicity, aggravation of asthma, sodium retention, hypertension, and resistance to antihypertensive medications due to high plasma concentration of the drug [16]. The injection route is also painful and can cause a sudden increase in plasma level of the drug and the associated side effects or complications [15]. Transdermal patches are medicated adhesive patches placed on the skin to deliver a certain dose of medication through the skin portals directly to the bloodstream [17]. Not undergoing the first-pass metabolism in the liver, reduced plasma concentration, and subsequently lower systemic toxicity and side effects are the main advantages of transdermal patches. Also, they are better accepted by patients [18] and can be particularly beneficial for patients with trypanophobia [19]. Several studies have evaluated the analgesic efficacy of NSAID transdermal patches for pain control following tooth extraction [18-21], periodontal surgery [22-24], maxillofacial surgical procedures [25], and endodontic treatment [26-29]. However, to the best of the authors’ knowledge, the efficacy of transdermal patches for orthodontic pain control has not been previously investigated. Also, controversy exists regarding the efficacy of transdermal patches. Three studies in the field of periodontology and pain control after periodontal flap surgery compared the analgesic efficacy of diclofenac sodium tablets and transdermal patches and showed that the patches had higher, equal, or lower analgesic efficacy than tablets [22-24]. Studies on pain control after tooth extraction also showed that the diclofenac transdermal patches had equal [19,30], or slightly lower efficacy than tablets in the first 24 hours after the procedure [15,22]. Additionally, diclofenac transdermal patches can have equal or lower analgesic efficacy compared with ketoprofen patches [18,21]. Studies on the efficacy of transdermal patches for endodontic pain control also showed almost equal analgesic efficacy of diclofenac tablets and patches, as well as ketoprofen patches and ibuprofen tablets [26,31]. Considering the significance of orthodontic pain control with minimal complications and side effects, this study aimed to compare the analgesic efficacy of diclofenac and ketoprofen transdermal patches versus ibuprofen tablets for pain control following initial archwire placement in orthodontic patients. The null hypothesis of the study was that no significant difference would be found in the analgesic efficacy of diclofenac and ketoprofen transdermal patches versus ibuprofen tablets for pain control following initial archwire placement in orthodontic patients. Materials and Methods This study was conducted at the Orthodontics Department of School of Dentistry, Guilan University of Medical Sciences from April 2024 to November 2024. The study protocol was approved by the ethics committee of the university (IR.GUMS.REC.1402.577), and registered in the Iranian Registry of Clinical Trials (#IRCT20190915044771N2). Trial design: A randomized clinical trial was designed in which patients received either diclofenac transdermal patches, ketoprofen transdermal patches, or ibuprofen tablets for pain control following archwire placement. The results were reported in accordance with the Consolidated Standards of Reporting Trials. Participants, eligibility criteria and settings: The inclusion criteria were patients requiring fixed orthodontic treatment of both the maxillary and mandibular arches, age range of 15 to 30 years, physical health with no systemic disease (ASA I), presence of 3-6 mm of crowding in both the maxillary and mandibular arches with no need for tooth extraction according to the Little’s Irregularity Index [32], no medication intake, no history of allergy, gastrointestinal bleeding, or discomfort following the intake of aspirin-like medications such as ibuprofen (NSAIDs in general), and having no problem taking ketoprofen, diclofenac, or ibuprofen. The exclusion criteria were patients who had taken analgesics during 24 hours prior to the treatment onset, illiterate patients (inability to read and write), those requiring restorative, endodontic, or extraction treatments, patients with spontaneous toothache or periodontal problems contraindicating orthodontic treatment, patients not willing to participate in the study, pregnancy or nursing, and those with a history of renal or hepatic diseases, or taking medications affecting the kidneys or the liver. Also, patients who did not take/use the assigned medication at the required time points according to the provided timetable or did not correctly report their pain score at the designated time points, patients with one or more brackets debonded in the first week after the treatment onset, and patients who required drug or analgesic intake for non-orthodontic reasons during the first week after the treatment onset were all excluded. The sample consisted of 60 patients between 15 to 30 years requiring fixed orthodontic treatment who were selected among those presenting to the Orthodontics Department of School of Dentistry, Guilan University of Medical Sciences during the aforementioned time period. Interventions: Written informed consent was obtained from all eligible participants prior to their enrollment. The consent form included important information about the study objectives, methodology, and advantages and possible side effects of medications. The patients were scheduled to undergo fixed orthodontic treatment at the Orthodontics Clinic of School of Dentistry of Guilan University of Medical Sciences by postgraduate students of orthodontics or orthodontists. Demographic information of patients was initially extracted from their records. All patients received orthodontic appliances including a buccal tube on first molars, brackets (0.022-inch MBT system), and 0.014-inch nickel-titanium archwires on both dental arches during a morning session. The patients were then randomly assigned to 3 parallel groups (n=20) with 1:1:1 allocation ratio using permuted blocks: A: Patients received 30 mg ketoprofen transdermal patches (Kefentech plaster 30mg, Jeil health science, Yongin-Si, South Korea) immediately after archwire placement, and also after 12 and 24 hours. B: Patients received 15 mg diclofenac transdermal patches (Defen Plaster 15 mg, Sinil Pharmaceutical Co, Seoul, Republic of Korea) immediately after completion of archwire placement, and also after 12 and 24 hours. C: Patients received 400 mg ibuprofen tablets (RAHA Pharmaceutical Co., Tehran, Iran) immediately after archwire placement and 8, 16, and 24 hours later. The abovementioned transdermal patches contain the lowest available dose internationally and also in Iran. Ibuprofen was used as the gold standard for reduction of orthodontic pain [33,34]. The patients in the ketoprofen and diclofenac groups were asked to apply the transdermal patch on a hairless area of the skin such as the arm or forearm immediately after archwire placement and also after 12 and 24 hours. In the ibuprofen group, the patients were asked to take 400 mg ibuprofen tablets immediately after archwire placement and also after 8, 16, and 24 hours. Also, all patients received an envelope containing 10 acetaminophen tablets (500 mg) as the rescue drug to take in case their pain was not subsided by the prescribed medication/patch. Also, they were asked to inform the researcher in case of using the rescue drug. Patients using the rescue drug were excluded from the study and were visited at the shortest possible time to find the cause of their severe pain. The patients were also requested to express their level of pain immediately after treatment, after 2 and 6 hours, at bedtime, after 24 and 48 hours, and also after 3 and 7 days following archwire placement using a numeric rating scale (NRS). They were asked to quantify their pain level by using a number between 0-10 that best described their experienced pain with 0 indicating no pain and 10 indicating the most excruciating pain possible. The NRS used in this study included both pictures and descriptions for an enhanced understanding [35]. To ensure that the patients completely understanded the method of using the medication, they were asked to open the envelope, and the method of use was verbally explained to them by the assistant. Next, the patients used the first dose of their medication after completion of bracket bonding and activation of #14 nickel-titanium archwire. Outcomes (primary and secondary): Orthodontic pain was the primary outcome in this study. Sample size calculation: The sample size was calculated to be a minimum of 16 patients in each group using the sample size calculation formula for ANOVA and pain variable in PASS 11 software, and considering an effect size of 0.60, study power of 0.95, significance level of 0.05, beta=0.04, mean value of 2.59 and standard deviation of 1.56 for the pain score according to a study by Farzanegan et al [36]. Considering 20% possible dropouts, the sample size increased to 20 patients in each group (a total of 60). Interim analyses and stopping guidelines: No interim analyses were performed and no stopping guidelines were established. Randomization: Using stratified permuted blocks, all eligible patients who consented to participate in the study randomly received an envelope containing the medication and instructions for use. The envelopes were administered by an assistant. Sixty patients underwent the randomization process, and their gender and type of medication were taken into account as the variables to randomly assign the patients into 3 groups (n=20 with 10 males and 10 females in each group). The medications were also labeled as A (ketoprofen), B (diclofenac) or C (ibuprofen). The envelopes were divided into two groups of blue and red. Female participants selected a red envelope and male participants selected a blue envelope. The medications and their instructions for use were placed in the envelopes according to the following sequences: Blue envelope blocks: ABC, ACB, BAC, BCA, CBA, CAB, ABC, ACB, BAC, BCA Red envelope blocks: CAB, CBA, ABC, ACB, BAC, BCA, ABC, ACB, CAB, CBA To ensure allocation concealment, sequentially numbered, sealed opaque envelopes were used [37]. Blinding: The orthodontist, researcher, and statistician were all blinded to the type of assigned medications to patients (their group allocation), and only the assistant who coded the envelopes was aware of their content. The patients could not be blinded due to the form of delivery of medications. Statistical analysis: Normal distribution of data was evaluated by the Kolmogorov-Smirnov test, and homogeneity of the variances was analyzed by the Levene’s test. Accordingly, quantitative variables were analyzed by the generalized estimating equation (GEE), Kruskal Wallis test, and Bonferroni test while qualitative variables were analyzed by the Chi-square or the Fisher’s exact test. In the GEE models, unstructured and exchangeable working correlation matrix structure were used along with the Corrected Quasi Likelihood under Independence Model Criterion. All statistical analyses were carried out using SPSS version 27 (SPSS Inc., IL, USA) at 0.05 level of significance. Participant flow: The sample consisted of 60 patients with a mean age of 19.93±4.64 years in three groups. Each group included 10 males and 10 females. The mean age was not significantly different among the three groups (P=0.972). Thus, the three groups were standardized in terms of age and gender. Figure 1 shows the CONSORT flow-diagram of patient selection and allocation. Harms: Only one patient developed gastrointestinal problems following the consumption of ibuprofen. Skin reactions or gastrointestinal problems were not observed in any patient in the ketoprofen or diclofenac group. Subgroup analyses: Table 1 compares the pain score among the three groups at different time points following the placement of archwire. As shown, no significant difference was observed among the three groups in pain score at any time point (P>0.05). Also, in all three groups, pain increased in the first 6 hours and then decreased at bed time. It increased again at bedtime until 24 hours; this increase was greater in the ibuprofen group compared with the other two groups. Pain experienced a descending trend from 48 hours to 7 days. GEE was applied to compare the trend of change in pain score among the three groups, which showed no significant difference (P>0.05). The overall pain score was the lowest in the ketoprofen group, followed by the ibuprofen, and then the diclofenac group; however, the difference did not reach statistical significance (Figure 2). Table 2 indicates the simultaneous effect of independent variables on the trend of pain score at the assessed time points. As indicated, only time had a significant effect on the trend of pain score (P0.05). Table 3 compares the number of patients with zero pain score in the three groups. The results showed no significant difference in this regard among the three groups at any time point (P>0.05). Discussion The present results showed that in the ketoprofen and ibuprofen groups, pain increased from 2 to 6 hours after archwire placement, decreased at bedtime, increased again after 24 hours, and then decreased from day 2 to day 7. An almost similar trend was also observed in the diclofenac group with the difference than the pain score remained unchanged at 24 hours. Increased pain score in the early hours after using the patches may be due to the fact that cutaneous absorption of drugs, unlike oral intake or injection, reaches its peak usually after 30 minutes to 2 hours, and is a gradual process. Also, the plasma concentration of topical medications such as transdermal patches containing NSAIDs is significantly lower than oral NSAIDs, and a longer time is required to reach a constant therapeutic plasma level [38]. Moreover, local inflammation due to the application of orthodontic forces at different parts of the oral cavity can aggravate pain before the medications can exert their anti-inflammatory effect [39]. Increased pain score in early hours after taking ibuprofen may be due to the time-consuming nature of its gastrointestinal absorption [5]. Ibuprofen needs to be taken periodically to ensure its optimal analgesic efficacy since it has a half-life of 1.8 to 2 hours [40]. Pain reduction at bedtime in all three groups can indicate that the plasma concentration of medications reached optimal level at bedtime [41]. It can also be due to the circadian rhythm since some inflammatory mediators such as interleukin-6 and prostaglandin E2 decrease at night, lowering the degree of inflammation and subsequently the pain score at night. An increase in level of melatonin at night can also affect pain perception since melatonin has anti-inflammatory and anti-oxidant effects as well, and can decrease pain by inhibiting the production of free radicals and inflammation. Furthermore, deep sleep decreases the activity of the sympathetic system and increases the activity of the parasympathetic system, potentially decreasing pain sensitivity [39,42]. At 24 hours, the pain score increased again, which was much higher in the ibuprofen group. The reason may be the constant plasma level of medications in the patch groups unlike the ibuprofen group [17]. Daily activities and mastication, and increased cortisol level in the morning can be other reasons for increased level of pain at 24 hours [43]. Gradual reduction of pain in all three groups from day 2 to day 7 is probably due to the reduction of inflammation and progression of the healing process since acute inflammation in response to tissue damage usually reaches its peak within the first 24-48 hours, and then the activity of anti-inflammatory factors such as interleukin-10 increases, causing a reduction in the immune response and enhancement of healing, resulting in pain relief [44]. In the present study, pain was assessed using the NRS due to its superiority to the visual analog scale (VAS), enabling easier parametrical analysis [45]. The results showed that the mean pain score was 2.51 at 2 hours, 3.53 at 6 hours, 3.01 at bedtime, and 3.43 at 24 hours. Following pain reduction starting from day 2, the mean pain score reached 0.28 at the end of the first week. These results were in line with the findings of a review study by Inauen et al [39]. They evaluated 37 randomized clinical trial (2,277 patients) regarding the pain score of patients at the leveling/alignment step using a 100 mm VAS, and reported fast onset of pain right after archwire placement. The mean pain score was 22.98 after 2 hours, 40.86 after 6 hours, 29.85 after 8 hours, and 42.42 after 24 hours. It then started to gradually subside, such that it reached 9 mm at the end of the first week. The trend of change in pain score in their study was close to that in the present study. However, the pain score was lower at 6 and 24 hours in the present study compared with theirs, which can be due to regular intake and higher efficacy of medications used in the present study compared with pain control methods in other studies. In the current study, orthodontic pain was moderate (NRS between 3-6) on day 1, which was in line with the results of Olteanu et al [42]. Literature is controversial regarding the effects of gender and age on perceived orthodontic pain. Olteanu et al. [42] showed higher pain score in males than females at the time of separator placement, cementation of bands, archwire activation, and elastic tension and increased with age. Unlike their study, the present results showed no significant effect of age and gender on the pain score. Similar results were reported by Ngan et al, [46] and Inauen et al [39]. Thus, gender- or age-related differences in pain perception may reflect cultural issues or personal experiences rather than actual physiological differences [47]. In the present study, the pain score was the lowest in the ketoprofen group, followed by the ibuprofen, and then the diclofenac group; but the difference was not significant. Thus, the null hypothesis of the study was accepted. The pain score was slightly, but not significantly, lower in the ketoprofen group than the diclofenac group. Both of these medications are NSAIDs, and decrease prostaglandin synthesis by inhibition of COX enzymes. In addition to the lower dosage of diclofenac than ketoprofen in the present study, these two medications have differences in selectivity for COX-1 and COX-2 enzymes, half-life, and chemical formulation, which may affect their efficacy and safety [27,48]. Diclofenac has a higher selectivity for COX-2, and is therefore used for cases of chronic inflammation such as osteoarthritis; therefore, it may have a lower efficacy than ketoprofen for management of orthodontic pain, which is due to acute inflammation; whereas, ketoprofen may be more effective for faster relief of acute pains such as orthodontic pain due to better penetration into the inflamed tissues and its effect on the minor inflammatory pathways such as leukotriene inhibition [48]. Also, diclofenac has a half-life of 2 hours but in transdermal patches, the medications are released slowly, and the effects may remain for 12-24 hours. Ketoprofen has a half-life of up to 2.5 hours but due to its stronger attachment to plasma proteins and greater penetration into the inflamed tissues, its effects may last longer (up to 48 hours) than those of diclofenac at the inflammation site [27]. Moreover, due to the polarity of its chemical structure, diclofenac has limited absorption through the skin, and carriers such as diethyl amine or fatty alcohols are often used to enhance its penetration. Thus, it has a slower absorption when applied through a transdermal patch. Ketoprofen has higher lipid solubility and can better penetrate deep into the tissues. It has a faster absorption through the skin and accumulates at the inflammation site in higher concentrations; these explanations justify lower pain score in the ketoprofen group [28]. Karunkar et al. [27] evaluated the analgesic efficacy of diclofenac and ketoprofen patches and showed that they were both effective for management of post-endodontic pain, and can be used as an alternative to diclofenac tablets for this purpose. Also, Dhanapal and Sureshbabu [29] suggested diclofenac transdermal patches as an alternative for management of mild to moderate endodontic pain with fewer systemic side effects. Zadsirjan et al. [26] showed that ketoprofen transdermal patches had a comparable efficacy to ibuprofen tablets for post-endodontic pain control in teeth with irreversible pulpitis. Furthermore, Mangal et al. [31] demonstrated comparable analgesic efficacy of diclofenac patch and tablets for post-endodontic pain control in single-rooted premolars with irreversible pulpitis. Despite different methodologies, the abovementioned results were in line with the current findings, highlighting the optimal comparable analgesic efficacy of diclofenac and ketoprofen patches. The optimal comparable analgesic efficacy of diclofenac and ketoprofen patches for management of post-extraction pain has also been reported [20,24,49]. In the present study, none of the patients in the patch groups experienced any gastrointestinal problem. In a study by Karunakar et al, [27] 1 out of 10 patients in the diclofenac patch group and none in the ketoprofen patch group developed gastrointestinal problems. Difference between their results and the present findings may be due to the administered dosage since the diclofenac patches in their study had 100 mg concentration (versus 15 mg in the present study). In the present study, no allergy or skin reaction occurred in any patient, which was similar to the study by Karunakar et al [27]. However, in a study by Zadsirjan et al, [26] one patient had a skin reaction to the first dose of ketoprofen patch, which may be due to the drug dosage (60 mg in their study versus 30 mg in the present study), their larger sample size (32 versus 20), and different patch structure due to different manufacturers. In the current study, no significant difference was found among the three groups in the frequency of patients with pain score zero. Similarly, Zadsirjan et al. [26] found no significant difference in this regard. Lack of a placebo group was a limitation of this study since inclusion of a placebo group would have enabled more accurate comparison of the analgesic efficacy of the tested medications. However, it was not performed since orthodontic pain is highly common after archwire placement, and having a placebo group was not ethical. Also, the pain level of patients was quantified subjectively, and inter-individual differences exist in pain perception which can affect the results. It should be noted that intake of NSAIDs during orthodontic treatment can interfere with the treatment process and decelerate orthodontic tooth movement [50]. Nonetheless, medication intake was limited to 1 day in the current study, and thus, its effect on orthodontic tooth movement was probably insignificant. Future studies with a larger sample size are required to increase the generalizability of the findings. Also, considering the increasing use of orthodontic aligners, future studies are recommended to focus on pain control methods in patients using aligners in comparison with fixed orthodontic treatment. Conclusion Considering the comparable analgesic efficacy of ibuprofen and the tested transdermal patches, diclofenac and ketoprofen patches may be used as an alternative to ibuprofen tablets for efficient pain control after initial archwire placement. Acknowledgments This study is derived from the doctoral thesis of a postgraduate orthodontics student at Guilan University of Medical Sciences. Author Contributions Yasamin babaee Hemmati: Project administration, Methodology, Supervision, Review & Editing Amirhossein Toghrolian: Conceptualization, Investigation, Writing-Editing, analyzed the data References 1. Ngan, P., Wilson, S., Shanfeld, J., & Amini, H. (1994). The effect of ibuprofen on the level of discomfort in patients undergoing orthodontic treatment. American Journal of Orthodontics and Dentofacial Orthopedics , 106 (1), 88–95. 2. Klasser, G. D., & Okeson, J. P. (2015). Role of the dentist in the management of orofacial pain. Pain Management , 5 (6), 407–411. 3. Alshammari, A. 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Comparison of the pain score among the three groups at different time points following the placement of archwire Time Ketoprofen Mean ± SD Diclofenac Mean ± SD Ibuprofen Mean ± SD P-value ⁕⁕ (F) 2 hours 2.50 ± 1.64 ab 2.60 ± 1.67 ac 2.45 ± 1.47 ac 0.857 (0.31) 6 hours 3.25 ± 1.65 a 3.90 ± 1.25 b 3.45 ± 1.82 b 0.394 (1.86) Bedtime 2.90 ± 1.80 ab 3.60 ± 1.53 ab 2.60 ± 1.79 ab 0.202 (3.20) 24 hours 3.62 ± 1.95 a 3.62 ± 1.46 ab 3.70 ± 1.81 b 0.238 (2.87) 48 hours 1.65 ± 1.39 b 1.55 ± 1.23 c 1.55 ± 1.23 c 0.978 (0.04) 72 hours 0.85 ± 1.23 c 0.65 ± 0.93 d 0.70 ± 0.66 d 0.641 (0.89) 7 days 0.35 ± 0.49 d 0.30 ± 0.66 e 0.20 ± 0.41 e 0.536 (1.25) P-value* (Wald Chi-Square) <0.001 (90.06) <0.001 (274.39) 0.05). ⁕⁕Kruskal Wallis Test\RL; * GEE (Bonferroni pairwise comparison) Table 2. Simultaneous effect of independent variables on trend of pain score at the assessed time points Group Ketoprofen -0.004 0.30 0.001 0.989 Diclofenac 0.22 0.29 0.61 0.435 Ibuprofen (R) - - - - Gender Female 0.35 0.24 2.04 0.153 Male (R) - - - - Age - -0.009 0.03 0.10 0.757 Time 2 hours 2.23 0.21 111.71 <0.001 6 hours 3.25 0.19 281.15 <0.001 Bedtime 2.75 0.20 184.89 <0.001 24 hours 3.15 0.20 245.25 <0.001 48 hours 1.30 0.14 88.69 <0.001 72 hours 0.48 0.10 22.74 <0.001 7 days (R) - - - - *GEE, R=Reference Table 3. Comparison of the number of patients with zero pain score among the three groups 2 hours 2 (10%) 3 (15%) 1 (5%) 0.877* 6 hours 1 (5%) 0 (0%) 1 (5%) 0.999* Bedtime 1 (5%) 0 (0%) 3 (15%) 0.625* 24 hours 2 (10%) 1 (5%) 1 (5%) 0.999* 48 hours 5 (25%) 4 (20%) 6 (30%) 0.819⁕⁕ 72 hours 9 (45%) 11 (55%) 8 (40%) 0.779⁕⁕ 7 days 13 (65%) 16 (80%) 16 (80%) 0.819⁕⁕ *: Fisher’s exact test; ⁕⁕:Chi-square test Figures Figure 1. CONSORT flow-diagram of patient selection and allocation Figure 2. Trend of change in pain score of orthodontic patients in the three groups Information & Authors Information Version history V1 Version 1 28 April 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords analgesics dermatology pain transdermal drug delivery Authors Affiliations Yasamin Babaee Hemmati View all articles by this author amirhossein toghrolian 0000-0002-4424-5785 [email protected] View all articles by this author Metrics & Citations Metrics Article Usage 746 views 324 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Yasamin Babaee Hemmati, amirhossein toghrolian. Analgesic efficacy of diclofenac and ketoprofen patches versus ibuprofen tablets for pain control after archwire placement in orthodontic patients. Authorea . 28 April 2025. DOI: https://doi.org/10.22541/au.174582202.28212902/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); Cited by Yasamin Babaee Hemmati, Amirhossein Toghrolian, Comparative Analgesic Efficacy of Diclofenac and Ketoprofen Transdermal Patches Versus Ibuprofen Tablets for Pain Control After Initial Archwire Placement in Orthodontic Patients: A Randomized Clinical Trial, Pain Research and Management, 2026 , 1, (2026). https://doi.org/10.1155/prm/9922008 Crossref Loading... 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