Ibuprofen plus caffeine in the treatment of tension-type headache

BACKGROUND: The effectiveness of caffeine as an adjuvant to ibuprofen has been documented in investigations of acute pain. Our objectives were to assess this agent in the treatment of tension-type headache and to establish clinical trial methods capable of assessing this agent in comparison with various tension headache treatments. Stopwatch technology was used for measurement techniques. METHODS: A randomized, double-blind, parallel, multicenter, single-dose, placebo- and active-controlled study included 301 subjects diagnosed with tension-type headache. Treatment groups included ibuprofen and caffeine, ibuprofen alone, caffeine alone, or placebo. Subjects measured onset of relief (both time to first perceptible relief and time to meaningful relief) after taking a single oral dose of their assigned medication. Pain intensity and pain relief were rated over a 6-hour study period. Overall evaluation was made on completion of all other ratings. RESULTS: Ibuprofen and caffeine administered together provided significantly greater analgesic activity than ibuprofen alone, caffeine alone, and placebo. Ibuprofen and caffeine administered together demonstrated significantly shorter times to meaningful improvement in headache relief than ibuprofen or placebo; significantly greater total analgesia than ibuprofen alone, caffeine alone, or placebo; and significantly greater peak relief than ibuprofen alone, caffeine alone, or placebo. Significantly more subjects obtained meaningful headache relief with ibuprofen and caffeine administered together than with ibuprofen alone or placebo. More patients reported complete headache relief with ibuprofen and caffeine administered together than with ibuprofen alone, caffeine alone, or placebo. Ibuprofen and caffeine administered together was rated significantly better by patients than either ibuprofen alone, caffeine alone, or placebo. No subjects ended participation in the study early because of adverse events. CONCLUSIONS: Sensitive methods have been introduced to assess differences in analgesia among over-the-counter analgesic agents in relieving tension-type headache pain. A double-blind study with this method suggests that ibuprofen and caffeine administered together provides greater analgesic effectiveness than either component alone.     

Solubilized ibuprofen: evaluation of onset, relief, and safety of a novel formulation in the treatment of episodic tension-type headache

OBJECTIVE: To evaluate the relative efficacy of a new solubilized formulation of ibuprofen compared with acetaminophen caplets. METHODS: This double-blind, randomized, parallel group study evaluated 154 subjects taking a single dose of solubilized ibuprofen, 400 mg; acetaminophen, 1000 mg; or placebo for the relief of episodic tension-type headache. Time to relief was measured using a stopwatch, and overall efficacy was measured using traditional categorical pain and relief scales. RESULTS: Ibuprofen capsules (liquigel), 400 mg, were significantly faster than both acetaminophen, 1000 mg, and placebo for all time-to-relief measures. Ibuprofen liquigel had a median time to first perceptible pain relief of 39 minutes compared with 47 minutes for acetaminophen and 113 minutes for placebo. For median time to meaningful relief, ibuprofen liquigel had a time of 39 minutes compared with 53 minutes for acetaminophen and more than 180 minutes for placebo (P相似文献   

Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain

Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen, aspirin, or their mixture. Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen. On a double-blind basis, a single oral dose of ibuprofen (50, 100, or 200 mg), a combination of ibuprofen, 100 mg, with caffeine, 100 mg, a combination of ibuprofen, 200 mg, with caffeine, 100 mg, or placebo was randomly assigned to 298 outpatients with postoperative pain after the surgical removal of impacted third molars. With a self-rating record, subjects rated their pain and its relief hourly for 8 hours. All active treatments were significantly superior to placebo, and the caffeine effect was significant for every measure of analgesia. Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone. The combination also had a more rapid onset and longer duration of analgesic action. The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti-inflammatory drugs other than acetaminophen or aspirin.     

Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study

OBJECTIVE: Compare the effectiveness of a combination analgesic containing acetaminophen, aspirin, and caffeine to that of ibuprofen in the treatment of migraine. METHODS: Multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study. A total of 1555 migraineurs were included in the analysis. No patients were excluded solely because of severity of symptoms or degree of disability. A single 2-tablet dose for each of the 3 treatment groups: a combination product containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg per tablet (AAC); ibuprofen 200 mg per tablet (IB); or matching placebo. The primary efficacy endpoint was the weighted sum of pain relief (PAR) scores at 2 hours postdose (TOTPAR2) and an important secondary endpoint was the time to onset of meaningful relief. RESULTS: There were 669 patients in the AAC group, 666 patients in the IB group, and 220 patients in the placebo group. The 3 treatment groups had similar demographic profiles, migraine histories, and baseline symptom profiles. While both active treatments were significantly better than placebo in relieving the pain and associated symptoms of migraine, AAC was superior to IB for TOTPAR2, as well as for PAR, time to onset of meaningful PAR, pain intensity reduction, headache response, and pain free. The mean TOTPAR2 scores for AAC, IB, and placebo were 2.7, 2.4, and 2.0, respectively (AAC vs. IB, P < .03). The median time to meaningful PAR for AAC was 20 minutes earlier than that of IB (P < .036). CONCLUSION: AAC and IB are safe, cost-effective treatments for migraine; AAC provides significantly superior efficacy and speed of onset compared with IB.     

Use of a fixed combination of acetylsalicylic acid,acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized,double-blind,placebo-controlled,crossover studies

Background

Most patients with episodic tension-type headache treat headache episodes with over-the-counter medication. Combination analgesics containing caffeine may be more effective and as well tolerated as monotherapy. The aim of this study was to evaluate the efficacy of the combination of acetylsalicylic acid, acetaminophen (paracetamol) and caffeine in episodic tension-type headache using recently recommended endpoints.

Methods

Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs. acetaminophen or placebo were pooled. Analysis populations were ‘all headache episodes’ and those with ‘severe pain at baseline’. Post-hoc defined primary endpoint: headache episodes pain-free at 2 h. Secondary endpoints: headache episodes pain-free at 1 h, headache response at 2 h (mild or no pain), degree of interference with daily activities.

Results

6,861 headache episodes were treated, including 2,215 severe headache episodes. The proportion of headache episodes pain-free at 2 h was significantly higher with the triple combination (28.5%) vs. acetaminophen (21.0%) and placebo (18.0%) (p < 0.0001), and similarly for those severe at baseline (20.2% vs. 12.1% and 10.8%; p ≤ 0.0003). A similar pattern of superiority was observed for secondary endpoints. The triple combination was generally well tolerated.

Conclusions

The combination of acetylsalicylic acid, acetaminophen and caffeine is effective and well tolerated in episodic tension-type headache, and significantly superior to acetaminophen with regard to being pain-free at 2 h, headache response at 2 h and ability to return to daily activities, even in those with pain rated severe at baseline.     

The role of rofecoxib, a cyclooxygenase-2-specific inhibitor, for the treatment of non-cancer pain: a review.

Rofecoxib was the first specific inhibitor of cyclooxygenase-2 (COX-2) approved for the treatment of acute pain. It has been shown to provide analgesia that is significantly better than placebo and has an onset of action and efficacy similar to that of traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen and ibuprofen. In addition, the analgesic efficacy of rofecoxib has been demonstrated to be superior to that of the opioid combination of codeine 60 mg/acetaminophen 600 mg in an acute dental pain model. For the treatment of acute pain, the efficacy of rofecoxib was further demonstrated in a study of patients who had undergone orthopedic surgery. Rofecoxib has been found to be as effective as naproxen sodium and more effective than placebo in studies evaluating its use for the treatment of primary dysmenorrhea. In patients with osteoarthritis (OA) of the knee or hip, rofecoxib is superior to placebo and similar to diclofenac and ibuprofen in relieving OA pain and improving physical function. Rofecoxib has also been shown to be superior to acetaminophen and celecoxib after 6 weeks of treatment for OA. The efficacy of rofecoxib has also been demonstrated in patients with rheumatoid arthritis and low back pain. The advantages of using COX-2-specific NSAIDs include convenient once-daily dosing schedule and improved safety compared with traditional NSAIDs. Two large outcomes studies, VIGOR and CLASS, have shown that gastric mucosal ulceration occurs significantly less often in patients taking COX-2-specific inhibitors than in those treated with ibuprofen, diclofenac, or naproxen and occurs with a similar incidence to that of placebo. Absence of any effect on platelet aggregation and bleeding time further distinguishes these agents from traditional NSAIDs. Because COX-2-specific inhibitors do not have an antiplatelet effect, they cannot be used as a substitute for low-dose aspirin for cardiovascular prophylaxis. Rofecoxib is a safe and highly effective alternative to previously available NSAIDs and should be considered for the treatment of acute pain conditions in adult patients, especially those at risk for developing gastrointestinal complications. It is preferred in the perioperative setting because of its analgesic efficacy and lack of platelet effects. Because of its more favorable gastrointestinal toxicity profile compared with nonselective NSAIDs, rofecoxib is safer in patients, especially older patients, for whom chronic anti-inflammatory or analgesic therapy is indicated.     

2-Arylpropionic acids. Role in pain therapy

The antipyretic analgesics still comprise the most widely used group of analgesic compounds. Until twenty years ago, aspirin, phenazone derivatives and acetaminophen had been used as standard remedies for intercurrent harmless pain conditions in connection with infections, trauma, small surgeries, but also for tension headache and other painful conditions. During the last decades, this group has been supplemented by a variety of 2-arylpropionic acids being primarily developed for the treatment of rheumatic pain and inflammation. Some of them (e.g. ibuprofen, ketoprofen and naproxen) have been given over-the-counter status in some countries because of their relative safety at low doses. Nevertheless, pharmacodynamic and pharmacokinetic differences among the various substances of this group make them suitable to a different degree for the treatment of pain conditions.     

A double-blind randomized study of an aspirin/caffeine combination versus acetaminophen/aspirin combination versus acetaminophen versus placebo in patients with moderate to severe post-partum pain

In a double-blind, randomized controlled trial among 500 post-partum patients experiencing moderate to severe pain, a single oral dose of an aspirin/caffeine combination (800 mg aspirin, 65 mg caffeine) provided significantly more pain relief at 2 hours than did a higher dose of an acetaminophen/aspirin combination (648 mg acetaminophen, 648 mg aspirin) and a higher dose of acetaminophen alone (1000 mg acetaminophen). At 3 and 4 hours, the acetaminophen/aspirin combination as well as the aspirin/caffeine combination were significantly superior to acetaminophen alone. At all times, all three drugs were significantly superior to placebo. There were no clinically significant adverse reactions. These results provide evidence of a potentiating effect of caffeine on aspirin's analgesic potency.     

The analgesic efficacy of ketorolac for acute pain

Ketorolac is a nonsteroidal anti-inflammatory drug, available in both oral and parenteral forms, that possesses significant analgesic potency. Its analgesic efficacy has been studied extensively for the treatment of moderate-to-severe pain in many clinical settings. Although ketorolac possesses significant analgesic potency, it has limited utility as an analgesic for the acute treatment of moderate-to-severe pain in the emergency department. Oral ketorolac has been shown to provide analgesia that is the same or better than aspirin, acetaminophen, and dextropropoxyphene with acetaminophen, and equal analgesia to most other commonly available oral analgesics, including ibuprofen and acetaminophen with codeine. Intramuscular ketorolac provides analgesia equivalent to commonly used doses of meperidine and morphine. However, its utility in acute pain, when rapid relief is necessary, is limited due to a prolonged onset to analgesic action (30–60 min) and a significant number of patients who exhibit little or no response, more than 25% in most studies. The use of intravenous ketorolac has been less well studied. It has analgesic potency but its utility in patients with moderate-to-severe pain is also limited because there is a significant percentage of patients who fail to obtain adequate relief. Ketorolac may be most useful in supplementing parenteral opiates.     

Comparison of Oral Ibuprofen and Acetaminophen with Either Analgesic Alone for Pediatric Emergency Department Patients with Acute Pain

BackgroundIbuprofen (Motrin; Johnson & Johnson) and acetaminophen (APAP, paracetamol) are the most commonly used analgesics in the pediatric emergency department (ED) for managing a variety of acute traumatic and nontraumatic painful conditions. The multimodal pain management of using a combination of ibuprofen plus acetaminophen has the potential to result in greater analgesia.ObjectiveWe compared the analgesic efficacy of a combination of oral ibuprofen plus acetaminophen with either analgesic alone for pediatric ED patients with acute pain.MethodsWe performed a randomized, double-blind superiority trial assessing and comparing the analgesic efficacy of a combination of oral ibuprofen (10 mg/kg dose) plus acetaminophen (15 mg/kg per dose) to either analgesic alone for the treatment of acute traumatic and nontraumatic pain in the pediatric ED. Primary outcomes included a difference in pain scores among the three groups at 60 min.ResultsWe enrolled 90 patients (30 per group). The difference in mean pain scores at 60 min between acetaminophen and combination groups was 0.30 (95% confidence interval [CI] −0.84 to 1.83); between ibuprofen and combination groups was −0.33 (95% CI −1.47 to 0.80); and between acetaminophen and ibuprofen groups was 0.63 (95% CI −0.54 to 1.81). Reductions in pain scores from baseline to 60 min were similar for all patients in each of the three groups. No adverse events occurred in any group.ConclusionsWe found similar analgesic efficacy of oral ibuprofen and acetaminophen in comparison with each analgesic alone for short-term treatment of acute pain in the pediatric ED, but the trial was underpowered to demonstrate the analgesic superiority of the combination of oral ibuprofen plus acetaminophen in comparison with each analgesic alone.     

Amitriptyline Is Effective in Chronic But Not in Episodic Tension-Type Headache: Pathogenetic Implications

The tricyclic antidepressant amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension-type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study. Amitriptyline significantly reduced ( P <0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache. Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.     

Butalbital in the treatment of headache: history, pharmacology, and efficacy

Analgesics containing butalbital compounded with aspirin, acetaminophen, and/or caffeine are widely used for the treatment of migraine and tension-type headache. The butalbital-containing compounds are efficacious in placebo-controlled trials among patients with episodic tension-type headaches. Despite their frequent clinical use for migraine, they have not been studied in placebo-controlled trials among patients with migraine. Barbiturates can produce intoxication, hangover, tolerance, dependence, and toxicity. Butalbital can result in intoxication that is clinically indistinguishable from that produced by alcohol. Butalbital-containing analgesics can produce drug-induced headache in addition to tolerance and dependence. Higher doses can produce withdrawal syndromes after discontinuation. Butalbital-containing analgesics may be effective as backup medications or when other medications are ineffective or cannot be used. Because of concerns about overuse, medication-overuse headache, and withdrawal, their use should be limited and carefully monitored.     

Efficacy of diclofenac sodium softgel 100 mg with or without caffeine 100 mg in migraine without aura: a randomized, double-blind, crossover study

OBJECTIVE: A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks. BACKGROUND: Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies. A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain, and may have advantages in migraine treatment. In addition, caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics. The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine). METHODS: The 3-period crossover study was designed to compare diclofenac softgel 100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute treatment of migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported headache relief at 60 minutes versus 12 (27%) of 45 subjects in the diclofenac softgel group, and 19 (41%) of 46 subjects in the diclofenac softgel plus caffeine group. Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects treated with placebo, 15 (33%) of 45 subjects treated with diclofenac softgel, and 14 (30%) of 46 subjects treated with diclofenac softgel plus caffeine. This result is highly statistically significant (chi22= 11.56, P=.003). Both the diclofenac plus caffeine (P <.03) and diclofenac only (P <.03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes. CONCLUSIONS: The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes. Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels.     

Ketoprofen (25 mg) in the symptomatic treatment of episodic tension-type headache: double-blind placebo-controlled comparison with acetaminophen (1000 mg)

Therapies in current use for episodic tension-type headache (ETTH) are often unsatisfactory. Few trials have been conducted to demonstrate efficacy of any of them. This multicenter placebo-controlled randomized parallel-groups study compared the analgesic efficacy of single oral doses of ketoprofen 25 mg and acetaminophen 1000 mg as outpatient treatment of 1 attack of ETTH. Efficacy was assessed by patients as pain relief on a diary-entered 7-point categorical scale. A total of 457 patients treated 348 attacks, 330 of which were evaluable. There were no serious adverse events (AEs); gastrointestinal AEs were most common on all treatments. Total relief from pain after 2 h was recorded by l6% of patients on placebo, 28% on ketoprofen, and 22% on acetaminophen. Worthwhile effect or total relief (all other responses were regarded as treatment failures) were recorded by 36% on placebo, 70% on ketoprofen ( p <0.001), 61% on acetaminophen ( p <0.001). The difference between ketoprofen and acetaminophen was not significant ( p =0.24). Various secondary efficacy measures confirmed superiority of both active treatments over placebo, with some trends for slightly better outcome on ketoprofen than on acetaminophen This study demonstrates that ketoprofen is an effective alternative to standard therapy in ETTH.     

Ibuprofen Versus Aspirin and Placebo in the Treatment of Muscle Contraction Headache

SYNOPSIS
One hundred eight patients with muscle contraction headaches completed a double-blind, randomized, parallel trial in which they took either ibuprofen 400 mg, ibuprofen 800 mg, a spirin 650 mg, or placebo for four successive headaches. Acetaminophen was allowed as a rescue analgesic. Intensity of headache pain was recorded pretreatment and three hours posttreatment. A Pain Intensity Difference (PID) score was calculated from the difference. Patients on ibuprofen (both doses) and aspirin had significantly lower pain scores and higher PID scores at three-hour follow-up than did patients on placebo. Physician's global assessment indicated that both doses of ibuprofen were significantly superior to placebo; aspirin was not. The highest number of side effects occurred with aspirin (26 complaints), followed by placebo (11), ibuprofen 400 mg (3), and ibuprofen 800 mg (2); all were minor. These results suggest that, for the treatment of muscle contraction headache, ibuprofen is significantly more effective than placebo and at least as effective as aspirin.     

Treating chronic tension-type headache not responding to amitriptyline hydrochloride with paroxetine hydrochloride: a pilot evaluation

CONTEXT: In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. OBJECTIVE: To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. DESIGN AND SETTING: Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. PARTICIPANTS AND INTERVENTION: Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. OUTCOME MEASURES: Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. RESULTS: In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. CONCLUSIONS: We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo.