Peak Pain Intensity Difference Research Articles

Efficacy and safety of lornoxicam vs ibuprofen in primary dysmenorrhea: a randomized, double-blind, double dummy, active-controlled, cross over study

ObjectivesStudy was planned to evaluate the efficacy and safety of lornoxicam in moderate to severe menstrual pain due to primary dysmenorrhea. Study designThis doubled blind, double dummy, randomized, comparable study of lornoxciam versus ibuprofen was conducted at Sir Takhtsinghji General Hospital, Bhavnagar, Gujarat, India. Total 57 primary dysmenorrhea participants having mean age±standard deviation (SD) of 19.2±2.08 were analyzed. The participants were randomly allocated to either lornoxicam 8mg or ibuprofen 400mg two times a day for maximum of three days on two consecutive menstrual periods. The different medication was taken on each cycle. The analgesic efficacy was compared by a total area under pain relief score to 4 and 8h, pain intensity difference, sum of pain intensity difference to 4 and 8h, peak pain intensity difference to 4 and 8h, peak pain relief to 4 and 8h, total medication consumption, rescue medication and participant global evaluation. Adverse effects were recorded in both groups. ResultsIn both treatments, efficacy parameters were significantly reduced at measured time points as compared to baseline. No significant difference was observed between lornoxicam and ibuprofen in terms of efficacy parameters: total area under pain relief to 4h (8.0±2.6 vs 8.3±2.7), total area under pain relief to 8h (22.4±4.6 vs 23.0±4.4), sum of pain intensity difference to 4h (−5.7±1.9 vs −6.0±2.0), sum of pain intensity difference to 8h (−17.5±3.3 vs −17.8±3.5), peak pain relief to 4h (3.4±0.8 vs 3.5±0.8), peak pain relief to 8h (3.9±0.5 vs 3.9±0.4), peak pain intensity difference to 4h (−2.6±0.7 vs −2.7±0.7), peak pain intensity difference to 8h (−3.3±0.6 vs −3.3±0.6). Total medication consumption, a requirement of rescue medication and global evaluation of efficacy were comparable in both groups. The incidence of adverse effect was also similar in both groups. ConclusionsLornoxicam appears to be a new therapeutic agent for the treatment of primary dysmenorrhea.

Efficacy and Safety of Etodolac-Paracetamol Fixed Dose Combination in Patients With Knee Osteoarthritis Flare-up: A Randomized, Double-blind Comparative Evaluation

To evaluate the efficacy and safety of etodolac-paracetamol combination in comparison with etodolac alone in patients with knee osteoarthritis (OA) flare-up. In this double-blind, double-dummy, randomized, comparative, multicentric, parallel group study, 220 patients of either sex in the age range of 40 to 70 years with an OA flare-up were randomized either to etodolac (300 mg)-paracetamol (500 mg) combination or etodolac (300 mg) alone twice a day for 10 days. Efficacy outcomes were an average daily pain intensity score on 11-point visual analog scale, Western Ontario and McMaster score (WOMAC), and Lequesne Severity Index; total pain relief score at 30 minutes, 1, 2, and 4 hours after first-dose administration; OA flare-up symptoms resolution; patient's and investigator's overall assessment of study treatments. Etodolac-paracetamol was significantly superior to etodolac alone in reducing pain intensity (P<0.001), achieving pain relief (P<0.05) during the first 4 hours after the study dose administration, and resolution of the clinical signs and symptoms of OA flare-up such as morning stiffness, swelling/inflammation, and erythema. The combination showed significantly greater improvement in WOMAC scores and Lequesne Severity Index (P<0.001) than in etodolac monotherapy. Peak pain intensity difference over a period of 10 days was also significantly (P<0.001) higher in combination-treated patients compared with monotherapy-treated patients. The combination had significantly better patient's and investigator's global efficacy assessment (P=0.001). Both treatments were well tolerated and safe in patients with OA flare-up. For the treatment of painful OA flare-ups, the etodolac-paracetamol combination can offer improved clinical outcomes by targeting multiple pain pathways. The results of the current study show that etodolac-paracetamol is more effective in the treatment of OA flare-up than etodolac alone.

Efficacy and safety of aceclofenac and drotaverine fixed-dose combination in the treatment of primary dysmenorrhoea: a double-blind, double-dummy, randomized comparative study with aceclofenac

Objective To evaluate the efficacy and safety of aceclofenac–drotaverine combination against aceclofenac alone in patients with primary dysmenorrhoea. Study design This double-blind, double-dummy, randomized, comparative, multicentric study enrolled 200 women (100 women in each arm) in the age range of 18–35 years with primary dysmenorrhoea at four centers. The patients were randomly allocated to either aceclofenac 100 mg–drotaverine 80 mg b.i.d or aceclofenac 100 mg alone b.i.d for a maximum of 3 days. Primary efficacy parameters were total area under pain relief (PR) score up to 4 and 8 h (TOPAR/4 and TOPAR/8). Secondary efficacy measurements were pain-intensity difference (PID), sum of PID over 4 and 8 h (SPID/4 and SPID/8), peak PID over 4 and 8 h and peak PR over 4 and 8 h, total study drug consumption, and patient's and investigator's global evaluation of the efficacy. Results Both treatments showed significant improvement in baseline values in all efficacy parameters. The combination was significantly superior to monotherapy in terms of TOPAR/4 (24.0 vs 18.54) ( p = 0.000) and TOPAR/8 (40.3 vs 35.2) ( p = 0.003), SPID/4 (−17.9 vs −13.88) ( p = 0.000) and SPID/8 (−31.06 vs −26.8) ( p = 0.001), peak PID/4 (−6.60 vs −5.75) ( p = 0.001) and peak PR/4 (8.26 vs 7.10) ( p = 0.000). At the end of 8 h, both treatments were comparable with respect to peak PID/8 and peak PR/8 ( p > 0.05). The total number of doses consumed by patients treated with combination therapy was less than with monotherapy (150 vs 168 doses). The combination was significantly superior to monotherapy with respect to patient's and investigator's global evaluation of the efficacy ( p = 0.002 and p = 0.001, respectively). Both treatments were well tolerated. Conclusion This study establishes the efficacy of aceclofenac–drotaverine combination in patients with primary dysmenorrhoea. The fixed-dose combination of aceclofenac and drotaverine should therefore be considered as a suitable, effective and well tolerated treatment option for primary dysmenorrhoea.

A randomized, multicentric, comparative evaluation of aceclofenac–paracetamol combination with aceclofenac alone in Indian patients with osteoarthritis flare-up

Objective: To evaluate efficacy and safety of aceclofenac–paracetamol combination against aceclofenac alone in patients with osteoarthritis (OA) flare-up. Methods: This open, randomized, comparative, multicentric, 10-day study enrolled 199 patients (aceclofenac 100 mg + paracetamol 500 mg bid: 101; aceclofenac 100 mg, bid: 98) with painful OA flare-up. Primary efficacy parameters were pain intensity difference (PID), sum of PID (SPID), and peak PID over 4 h (0.5, 1, 2, 4 h) after first dose of study medication. Secondary efficacy measurements were mean pain intensity scores from day 1 to day 10, WOMAC scores, changes in baseline signs and symptoms, and patient's and investigator's overall efficacy assessment. Results: Both treatments showed significant improvement in their baseline values in all efficacy parameters. The combination was superior over monotherapy in terms of PID ( -0.54 vs -0.23, -1.23 vs -0.72, -1.73 vs -1.23 and -1.94 vs -1.43 at 0.5, 1, 2 and 4 h respectively), SPID ( -5.46 vs -3.63) and peak PID ( -2.08 vs -1.56; p < 0.05). At the end of therapy, both treatments were comparable (p > 0.05) with respect to average pain intensity from day 1 to day 10, changes in WOMAC scores and resolution of baseline signs and symptoms. The combination was significantly superior to monotherapy with respect to the patients' and investigators' overall efficacy assessments (p = 0.035 and p = 0.009 respectively). Conclusion: The findings of this open-label, comparative study in Indian patients demonstrates that aceclofenac–paracetamol combination is effective and well tolerated in relieving OA flare-up pain. The combination showed rapid pain relief compared with monotherapy which is desirable by such patients and, hence, this combination can play an important role in the management of acute painful OA flare-up.

Oral naltrexone to enhance analgesia in patients receiving continuous intrathecal morphine for chronic pain: A randomized, double-blind, prospective pilot study

Years' worth of observations suggest that morphine has both inhibitory and excitatory actions, and that selective blockade of excitatory effects by low doses of opioid antagonists (e.g., naltrexone) may paradoxically enhance morphine analgesia. The purpose of this pilot study was to evaluate and compare the analgesic efficacy and safety of two different low doses of oral naltrexone given in addition to chronic intrathecal morphine infusions in patients with chronic nonmalignant pain (CNMP). After institutional review board approval, 15 patients with CNMP receiving continuous intrathecal morphine were admitted into a prospective, randomized, double-blind, placebo-controlled, seven-day pilot study. Patients were randomized into three treatment groups based on oral naltrexone dose: 100 microg (Group A, n = 3), 10 microg (Group B, n = 7), or placebo (Group C, n = 5). All patients continued with their constant intrathecal morphine infusion, and in addition they received one capsule of study medication every 12 hours for seven days. Other analgesics or coanalgesics were kept at a constant dose level throughout the study. Patients rated pain scores (visual analogue score [VAS]; 0 = no pain, 10 = worst pain imaginable) and side effects three times daily throughout the study period. Efficacy measures included pain intensity difference (PID) scores, constructed so that positive scores indicate a reduction in pain intensity and negative scores indicate a worsening of pain. Fifteen patients (six male, nine female) with a mean (SD) age of 55 (10) years and weight of 81 (21) kg completed the study. The mean (SD) baseline VAS pain intensity rating was similar in all three groups (6.8 [1.5]). Baseline pain VAS score minus the lowest daily pain VAS score yielded the peak PID score. The peak PID score from Day 1 was statistically (p < 0.05) highest (median PID score: 5.9) in Group A compared with Group C. There was a trend in PID scores across Days 2 through 7, with median PID scores higher (i.e., greater pain relief p = 0.07) in Group A. In the daily global pain assessments, the pain scores across Days 2 through 7 approached significance (least pain) in Group A compared to Group C (p = 0.07) or B (p = 0.08). Side effects were common (93 percent of patients), minor (headache, nausea, sedation, dry mouth), and similar across treatment groups. No serious adverse events were observed, and no evidence of opioid withdrawal was seen. 1) Patients with chronic pain who received oral naltrexone 100 microg BID in addition to their chronic intrathecal morphine infusions demonstrated the greatest improvement (p = 0.07) in their daily pain scores. Because of the small sample size, the results did not reach traditional levels of significance. 2) Side effects were common, minor, and similar across treatment groups. 3) No serious adverse events were recorded. 4) No evidence of opioid antagonist toxicity or opioid withdrawal was observed.

Analgesic efficacy and tolerability of oxycodone 5 mg/ibuprofen400 mg compared with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg in patients with moderate to severe postoperative pain: A randomized, double-blind, placebo-controlled, single-dose, parallel-group study in a dental pain model

Background: Combination therapy has been widely By combining 2 drugs with different mechanisms of action, such therapy provides additive analgesic effects while reducing the risk for adverse effects. Objective: This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo in a dental pain model. Methods: This was a multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group, single-dose study in patients experiencing moderate to severe pain after surgical removal of ≥2 ipsilateral impacted third molars. Patients were randomly assigned to receive oxycodone 5 mg/ibuprofen 400 mg, oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, or placebo. The primary outcome measures were total pain relief through 6 hours after dosing (TOTPAR 6), sum of pain intensity differences through 6 hours (SPID 6), and adverse events. Secondary efficacy measures included SPID 3 and TOTPAR 3, peak pain relief, peak pain intensity difference, time to onset of pain relief, time to use of rescue medication, proportion of patients reporting pain half gone, and the patient's global evaluation. Results: Two hundred forty-nine patients (43.5% male; 87.5% white; mean age, 19.1 years; mean body weight, 153.6 pounds) were randomized to treatment as follows: 62 to oxycodone 5 mg/ibuprofen 400 mg, 61 to oxycodone 5 mg/acetaminophen 325 mg, 63 to hydrocodone 7.5 mg/acetaminophen 500 mg, and 63 to placebo. Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo (mean [SD] TOTPAR 6, 14.98 [5.37], 9.53 [6.77], 8.36 [6.68], and 5.05 [6.49], respectively; P < 0.001, oxycodone 5 mg/ibuprofen 400 mg vs all other treatments). SPID 6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg compared with all other treatments (mean: 7.78 [4.11], 3.58 [4.64], 3.32 [4.73], and 0.69 [4.85]; P < 0.001). Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points ( P < 0.001, all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [ P = 0.006]), with the exception of the time to onset of analgesia. The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg (6.5% and 3.2%, respectively) and placebo (3.2% and 1.6%). Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg ( P = 0.011 and P = 0.009, respectively) but not with hydrocodone 7.5 mg/acetaminophen 500 mg. Conclusions: In this study in patients with moderate to severe pain after surgery to remove impacted third molars, oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/nonopioid combinations tested, and was associated with fewer adverse events.

TQ-1011 is superior to morphine and placebo in alleviating moderate to severe postsurgical pain

TQ-1011 is an injectable non-opioid analgesic under clinical investigation for the treatment of acute postsurgical pain. This single dose, single-center, double blind, randomized study compared the analgesic efficacy and safety of intravenous (IV) doses of TQ-1011, 50 and 100 mg, with morphine sulfate 4 mg and placebo in patients with moderate to severe postsurgical pain following third molar surgery. Each treatment was administered over 2 minutes. One hundred and thirty patients (44 M, 86 F) with moderate or severe post-surgical pain were assessed. Pain intensity (using standard categorical and visual analog scales) and pain relief (categorical only) were assessed at baseline and 12 time points over 8 hours following dosing. Times to perceptible and meaningful pain relief were measured by stopwatch and were used to determine time to onset of analgesia. The a priori primary measure of efficacy was Total Pain Relief (TOTPAR) 0–4. Secondary measures of efficacy included TOTPAR (at other time points), Sum of Pain Intensity Difference (SPID), Sum of Pain Relief Intensity Difference (SPRID), Time to First Rescue, Peak Pain Intensity Difference (PPID), Peak Pain Relief (PPR), Time to Confirmed Perceptible Pain Relief (onset) and Patient Global Evaluation. Safety was assessed during the study and at follow-up 5–10 days post-treatment by chemistry, hematology, urinalysis, vital signs and volunteered or observed adverse effects. All efficacy analyses were performed on the Intent-to-Treat population. TQ-1011 50 mg and 100 mg were well tolerated. Both doses provided rapid onset of effect (5 and 7 minutes) and significant analgesic efficacy. The TOTPAR 0–4 for TQ-1011 50 mg, 100 mg, morphine 4 mg and placebo were 10.6, 11.6, 2.7 and 2.8, respectively. On every measure of efficacy, TQ-1011 50 mg and 100 mg IV were superior to IV morphine 4 mg and placebo (p<0.001). This research was sponsored by TheraQuest Biosciences.

Comparison of rofecoxib and oxycodone plus acetaminophen in the treatment of acute pain: A randomized, double-blind, placebo-controlled study in patients with moderate to severe postoperative pain in the third molar extraction model

Background: Opiates, acetaminophen, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2-selective inhibitors such as rofecoxib are used in the treatment of acute pain because of their anti-inflammatory and/or analgesic properties. Rofecoxib has demonstrated an improved gastrointestinal safety profile compared with nonselective NSAIDs. Objective: The aim of this study was to compare the analgesic efficacy and tolerability profile of rofecoxib 50 mg with those of the centrally acting, nonsalicylate, opiate/nonopiate analgesic combination oxycodone/acetominophen 5 325 mg in patients with pain after dental surgery. Methods: In this randomized, double-blind, placebo- and active comparator-controlled study, patients experiencing moderate to severe postoperative pain after extraction of ≥2 third molars (including ≥1 mandibular impaction) received a single oral dose of rofecoxib 50 mg, oxycodone/acetaminophen 5 325 mg , or placebo. End points included total pain relief over 6 hours (TOPAR6, the primary end point) and 4 hours (TOPAR4), patient's global assessment of treatment at 6 hours (GLOBAL6) and 24 hours (GLOBAL24), summed pain intensity difference over 6 hours (SPID6), onset of analgesic effect (time to perceptible/meaningful pain relief, using a 2-stopwatch method), peak pain relief (PEAKPR), peak pain intensity difference (PEAKPID), and duration of analgesic effect (time to use of rescue analgesia). Results: Two hundred twelve patients (63% female, 37% male; 76% white, 24% other; mean [SD] age, 20.9 [4.4] years; age range, 16–41 years) were enrolled in the study and received a single oral dose of rofecoxib 50 mg (n = 90), oxycodone/acetaminophen 5 325 mg (n = 91), or placebo (n = 31). The analgesic effect of rofecoxib was significantly greater than that of oxycodone/acetaminophen at P < 0.001 for TOPAR6, TOPAR4, GLOBAL6, GLOBAL24, and SPID6; at P < 0.010 for PEAKPR and PEAKPID; and at P < 0.001 for median time to use of rescue analgesia. Significantly fewer patients in the rofecoxib group (72.2%) took rescue analgesia within 24 hours postdose compared with the oxycodone/acetaminophen group (94.5%; P < 0.001) and the placebo group (96.8%; P < 0.02). Both active treatments were similar with respect to onset of analgesic effect. Both were generally well tolerated; the overall incidence of adverse experiences in the rofecoxib, oxycodone/acetaminophen, and placebo groups was 51.1%, 64.8%, and 48.4%, respectively. Rofecoxib was associated with a significantly lower incidence of nausea (18.9% vs 39.6%; P < 0.001) and vomiting (6.7% vs 23.1%; P < 0.001) compared with oxycodone/acetaminophen. Conclusions: In study patients with moderate to severe pain after dental surgery, rofecoxib 50 mg had a greater analgesic effect than oxycodone/acetaminophen 5 325 mg and was associated with less nausea and vomiting.

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

Background: Rofecoxib and celecoxib, selective cyclooxygenase-2 inhibitors, have analgesic efficacy similar to that of nonselective nonsteroidal anti-inflammatory drugs. Objective: This study was designed to confirm earlier findings that the overall analgesic efficacy of rofecoxib 50 mg was superior to that of celecoxib 200 mg and to extend the comparison to include celecoxib 400 mg. Methods: In this single-center, randomized, double-blind, placebo- and active-comparator-controlled, parallel-group, single-dose study, patients who experienced moderate or severe pain after surgical extraction of at least 2 third molars received a single oral dose of either rofecoxib 50 mg, celecoxib 400 mg, celecoxib 200 mg, ibuprofen 400 mg, or placebo. Patients recorded scores of pain intensity, pain relief, and global assessment at prespecified time intervals throughout the 24-hour period after dosing. The end points were total pain relief (TOPAR) score over 8 hours (TOPAR8; primary end point), TOPAR score over 12 hours (TOPAR12), sum of pain intensity difference (SPID) over 8 and 12 hours (SPID8 and SPID12), patient's global assessment of study drug at 8 hours, time to confirmed perceptible pain relief (ie, time to onset of analgesic effect), peak pain intensity difference (PID), peak pain relief, time to first dose of rescue medication (ie, duration of analgesic effect), and percentage of patients using rescue medication. Results: A total of 482 patients (358 females, 124 males; mean age, 22.1 years) were enrolled. Rofecoxib 50 mg ( n = 151 patients) demonstrated significantly greater overall analgesic efficacy compared with celecoxib 400 mg ( n = 151), as measured by TOPAR8 (least squares mean [SE] 17.2 [0.8] vs 15.0 [0.8]; P < 0.05) and TOPAR12 (25.3 [1.2] vs 21.0 [1.2]; P < 0.05), as well as a significantly longer duration of analgesic effect ( P < 0.05). Time to onset of analgesic effect and peak analgesic effect were similar for rofecoxib 50 mg and celecoxib 400 mg. Rofecoxib also showed significantly greater overall analgesic efficacy than did celecoxib 200 mg ( n = 90) including greater TOPAR8 scores (17.2 [0.8] vs 11.5 [1.1]; P < 0.001), faster onset of analgesic effect ( P < 0.001), greater peak analgesic effect ( P < 0.001 for peak pain relief and peak PID), and longer duration of analgesic effect ( P < 0.001). The overall analgesic efficacy of rofecoxib 50 mg was similar to that of ibuprofen 400 mg ( n = 45), except that the duration of analgesic effect of rofecoxib 50 mg was significantly longer ( P < 0.001). All active treatments produced significantly greater overall analgesic efficacy compared with that of placebo ( P < 0.001 for all scores [TOPAR8, TOPAR12, SPID8, SPID12, and patient's global assessment] for all study drugs). The adverse-events (AE) profile was generally similar in all treatment groups. The 3 most common AEs were nausea, postextraction alveolitis, and vomiting. Conclusions: In this study, rofecoxib 50 mg provided generally superior overall analgesic efficacy compared with that of celecoxib 400 and 200 mg, including a significantly longer duration of analgesic effect. The overall analgesic efficacy of rofecoxib 50 mg was generally similar to that of ibuprofen 400 mg, except for a significantly longer duration of analgesic effect.

Myth: codeine is a powerful and effective analgesic.

Patients look to physicians not only to prevent and treat disease, but also to alleviate pain and suffering. Pain is the most common complaint among patients seen in the emergency department.1 A widely held belief is that codeine is a powerful and effective analgesic. The classic therapeutic regimen, endorsed by the American Society of Anesthesiologists Task Force on Pain Management, is to begin with nonopiate analgesia and to add opiate therapy if the level of pain control proves to be inadequate.2 The most common prepackaged combination therapy is codeine with acetaminophen (Tylenol #3 or #4).3 The underlying theory of this plan is that using 2 drugs with different mechanisms of action will, in essence, attack the problem from 2 sides. Unfortunately, studies have shown that this combination is at best only slightly more efficacious than nonopiate analgesia alone and results in a greatly increased number of adverse side effects. In a systematic literature review and meta-analysis of 29 published trials, de Craen and colleagues examined the change in both efficacy and safety when codeine was added to paracetamol (acetaminophen) for the relief of pain.4 Multiple reviewers were used to assess all studies, and 13 predefined methodologic criteria were applied to assess the quality of each trial. Pain intensity and relief were quantified through visual analog scales. In most studies, 60 mg of codeine was administered; the dosage of paracetamol ranged from 400 to 1,000 mg. Results of the pooled analysis of the 19 single-dose trials showed that adding codeine leads to an increase in analgesic effect of only 5%, as measured by the sum peak intensity difference, and produces similar results in peak painintensity difference, total pain relief, and peak pain relief. While the single-dose studies showed a similar incidence of side effects between the 2 groups (pooled rate ratio = 1.1, 95% confidence interval 0.8-1.4), multidose studies showed a significant increase in side effects when codeine was added (pooled rate ratio = 2.5, 95% confidence interval 1.5-3.5). Boreau et al reported similar findings from a randomized, double-blind, multicenter study in which they compared the use of acetaminophen (400 mg) plus codeine (25 mg) with aspirin (1000 mg) and with placebo in the treatment of acute migraine headache in 198 patients.5 Response was measured with a visual analog scale in which a patient was asked to mark the intensity of his or her pain on a 100-mm line where 0 is “no pain” and 100 is “worst possible pain.” Baseline pain levels ranged from 55.9 to 59.6. Two hours after treatment was administered, the mean pain scores were 36.6 and 39.3 for aspirin and for acetaminophen plus codeine, respectively, with a placebo value of 53.8. Side-effect profiles were similar in the 2 treatment arms of this study. Analgesic combinations with hydrocodone bitartrate appear to be more effective than those with codeine. Palangio et al performed a randomized, double-blind, multicenter study in which 429 patients were randomly assigned to receive either 1- or 2-tablet doses of a hydrocodone (7.5 mg) plus ibuprofen (200 mg) combination or a 2-tablet dose of a codeine (30 mg) plus acetaminophen (300 mg) combination.6 Patients who received the 2-tablet hydrocodone plus ibuprofen treatment reported greater daily pain relief than those who received either of the other 2 combinations. In addition, patients receiving codeine were more likely to stop therapy because of side effects. The myth that codeine is a potent and efficacious analgesic must be exposed so that clinicians can make more rational choices when managing and treating pain.

Analgesic efficacy of intranasal butorphanol (Stadol NS) in the treatment of pain after dental impaction surgery

Purpose: This study evaluated the safety and efficacy of increasing doses of intranasal butorphanol (Stadol NS, Bristol-Myers Squibb, New York, NY) compared with placebo in controlling moderate to severe pain after removal of bony impacted third molars. Patients and Methods: This single-dose, double-blind, parallel-group, dose\\Nresponse trial compared the efficacy and safety of 4 doses of intranasally administered butorphanol tartrate and placebo in controlling moderate to severe pain after the removal of impacted third molars in 151 patients. The study was conducted at 2 sites. The patients were randomly assigned to receive 1 dose of butorphanol tartrate: 0.25 mg (n = 31), 0.5 mg (n = 29), 1.0 mg (n = 30), 2.0 mg (n = 30), or placebo (n = 31). Medication was administered with a metered-dose spray pump. Patients rated pain intensity (PI), pain relief (PAR), pain half gone (PHG), and adverse events at 0.25, 0.5, 1, 2, 3, 4, 5, and 6 hours after treatment. At the end of the study period or before rescue medication (ibuprofen, 400 mg, or acetaminophen, 1,000 mg), patients provided an overall assessment (GLOBAL). Results: A linear dose-response regression (P ≤ .05) was observed for the means of pain intensity difference (PID), PAR, and PHG at 0.25, 0.5, and 1 hour, and for sum of pain intensity differences (SPID), sum of pain relief (TOTPAR), peak PID and PAR, and GLOBAL evaluation. The 1.0- and 2.0-mg groups experienced greater pain relief compared with placebo (P = .05) during the first hour after drug administration. The 1.0- and 2.0-mg groups had significantly better GLOBAL evaluations than the placebo group, but were not significantly different from placebo for time until remedication (TREMED). Incidence and severity of the most common adverse events were dose-related. Two severe adverse events (drowsiness and dizziness) occurred after the 2.0-mg dose. Conclusion: Intranasal butorphanol effectively relieved postsurgical dental pain, with a rapid onset within 15 minutes, and seems to be a promising addition to the current armamentarium of opioid analgesics. As with other opioids, it should be used cautiously in an outpatient setting. © 2000 by American Association of Oral and Maxillofacial Surgeons

Rofecoxib, a specific cyclooxygenase-2 inhibitor, in primary dysmenorrhea: a randomized controlled trial

Objective: To determine whether rofecoxib is effective for treating primary dysmenorrhea and whether cyclooxygenase-2 is involved in the pathophysiology of primary dysmenorrhea. Methods: A double-masked, randomized, placebo and active-comparator–controlled clinical trial including 127 subjects with histories of primary dysmenorrhea was conducted in an outpatient clinical research center. Subjects were randomly assigned to placebo, rofecoxib 25 or 50 mg followed by 25 mg every 24 hours as needed, or naproxen sodium 550 mg every 12 hours as needed for up to 3 days. Subjects took all four treatments in a balanced, complete-block, crossover design. Measurements included self-administered questionnaires of analgesic efficacy, spontaneous reports of adverse experiences, physical examinations, and laboratory safety tests. Results: Rofecoxib 25 and 50 mg provided analgesic efficacy greater than placebo ( P ≤ .006) for the primary endpoint of total pain relief over the first 8 hours. For other efficacy endpoints (sum of the pain intensity difference over the first 8 hours, subject’s global evaluation, peak pain relief, peak pain intensity difference, and time to remedication) both doses of rofecoxib were better than placebo ( P ≤ .006) and were not distinguishable from naproxen sodium for all efficacy endpoints. All treatments were well tolerated. Conclusion: Rofecoxib effectively treated primary dysmenorrhea, and cyclooxygenase-2–derived prostanoids play a role in the pathophysiology of primary dysmenorrhea.

Comparative Efficacy of Oral Ibuprofen-Arginine, Intramuscular Magnesic Dipyrone and Placebo in Patients with Postoperative Pain Following Total Hip Replacement

The comparative clinical efficacy and tolerability of oral ibuprofen-arginine 400mg, intramuscular dipyrone 2g and placebo were assessed in the control of postoperative pain in 106 patients who underwent surgery for a total hip replacement. Pain intensity was assessed at baseline and at 10, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes after treatment on a visual analogue scale ranging from no pain (0mm) to unbearable pain (100mm). Pain intensity was reduced in both active treatment groups from mean levels of 63mm (ibuprofen-arginine) and 62mm (dipyrone) to 22mm and 17mm, respectively, with a decrease of approximately 70% at the end of the study period, showing a decrease of 50% after the first 60 minutes. In contrast, pain levels in the placebo group (57.8mm) were reduced to 36.6mm within the first hour and to 32mm (<50%) at the end of the study. The peak pain intensity difference from baseline in patients receiving oral ibuprofen-arginine, intramuscular dipyrone and placebo was 51, 50 and 35mm, respectively. Statistically significant differences were observed between active treatments and placebo, but not between active treatments. No significant differences were observed between treatment groups with regard to the number of patients requesting rescue medication. 56% of patients of the ibuprofen-arginine group, 66% of the dipyrone group and only 21 % of the placebo group rated their medication as excellent or very good. With regard to tolerability, during the whole study period only 2 cases of headache were reported, one in the ibuprofen-arginine group and one in the placebo group. Data from this study showed that oral ibuprofen-arginine exhibits similar analgesic efficacy to intramuscular dipyrone. Therefore, oral ibuprofen-arginine may prove to be a useful alternative to parenteral analgesic agents in the treatment of postoperative pain following total hip replacement.

Double-masked, single-dose comparison of bromfenac sodium, acetaminophen plus oxycodone, and placebo after oral surgery

In this double-masked, parallel-group study, patients with moderate or severe pain after surgical removal of one or more impacted third molars were randomly assigned to receive a single dose of bromfenac 25 mg or 50 mg, acetaminophen 650 mg plus oxycodone 10 mg (APOX), or placebo. Patients reported their pain intensity at baseline and at regular intervals for up to 8 hours after receiving the study medication. The following efficacy measurements were collected or derived from patient assessments: hourly pain relief, peak pain relief, total pain relief (TOPAR), hourly pain intensity difference (PID), peak PID, and summed PID (SPID). Bromfenac 25 mg or 50 mg and APOX were significantly superior to placebo for each efficacy variable. The three active drug treatments were comparable up to 3 hours after administration: bromfenac 25 mg was significantly better than APOX at hour 4, and bromfenac 50 mg was superior to APOX for all hourly variables at hours 4 to 8. Mean 8-hour TOPAR and SPID scores demonstrated that bromfenac 25 mg was at least as effective as APOX, whereas bromfenac 50 mg was significantly superior to APOX. As compared with APOX or placebo, significantly more bromfenac-treated patients had global assessments of excellent or very good. Bromfenac was well-tolerated and comparable to placebo with respect to treatment-emergent study events (adverse events that either appeared or worsened after administration of the study drug). In contrast, APOX produced significantly more study events than bromfenac or placebo, including digestive events (eg, nausea or vomiting) and nervous system events (eg, dizziness or somnolence). These results demonstrate that single oral doses of bromfenac were at least as effective as APOX in providing pain relief after oral surgery. Bromfenac produced a longer duration of analgesic action than APOX, with a comparable short time to onset of action.

Double-blind comparison of meclofenamate sodium plus codeine, meclofenamate sodium, codeine, and placebo for relief of pain following surgical removal of third molars

A single-dose, randomized, double-blind, parallel-treatment study was performed in 200 outpatients with acute pain caused by the surgical removal of impacted third molars. Meclofenamate 100 mg plus codeine 60 mg, meclofenamate 50 mg plus codeine 30 mg, meclofenamate 100 mg, codeine 60 mg, and placebo treatment groups were compared for sum of pain intensity differences, peak pain intensity difference, sum of pain relief scores, peak pain relief, number of observations at which pain was half relieved, overall evaluation of effectiveness, and time to remedication with a backup analgesic. Meclofenamate 100 mg plus codeine 60 mg was significantly more effective ( P < .005) than codeine 60 mg for all variables except number of observations at which pain was half relieved. Both meclofenamate-codeine combinations and meclofenamate 100 mg alone were significantly more effective ( P < .005) than placebo for all variables. Eleven adverse experiences were reported in 7 patients (3.5%); the most common was somnolence in 1 patient receiving meclofenamate 100 mg plus codeine 60 mg, in 2 treated with meclofenamate 50 mg plus codeine 30 mg, and in 1 treated with codeine 60 mg.