How Good are NSAIDs as analgesics? ================================== --Keith Conover, M.D., FACEP (text submitted to a long emed-l Internet discussion) I won't discuss the methodology of the studies except that they all seemed adequate, except for possibly some drug company funding. OK, I found that most of the evidence supported the ideas that: * NSAIDs control pain that is about twice as severe as the most severe pain that aspirin (ASA) or acetaminophen (paracetamol, Tylenol), and * NSAIDs will do about twice a good a job of controlling pain as will ASA or acetaminophen for pain of a severity for which they both will have some effect. ------------------------------------------------------------------- * First, let me dispose of what might be seen as dissenting evidence. There is a single study that suggests that ASA 600 mg + caffeine 60 mg works as well as ibuprofen 200 mg in a dental pain model. However, the caffeine may well have potentiated the effect of the ASA so I discount this study. 1. [Habib S, Matthews RW, Scully C, Levers BGH, Shpherd JP. A study of the comparative efficacy of four common analgesics in the control of postsurgical dental pain.Oral Surg Oral Med Oral Pathol 1990;70:559-63.] ------------------------------------------------------------------- * Next, there are studies that confirm that ASA and acetaminophen are about equipotent for mild pain (and, roughly, as are most common oral narcotics). And, that narcotics and acetaminophen or ASA have additive effects. This article also points out that oxycodone (as in Percocet) is stronger than hydrocodone (as in Vicodin), which in turn is stronger than codeine (as in Tylenol #3). And it also shows that Darvon isn't very good. 2. [Beaver WT. Aspirin and acetaminophen as constitutents of analgesic combinations. Arch Intern Med 1981;141:293-300.] This study also shows that shows that acetaminophen and a narcotic such as hydrocodone or oxycodone are about equipotent for mild pain, but that the combination of the two is additive. (Interestingly acetaminophen 500 mg was superior to oxycodone 5 mg!) ------------------------------------------------------------------- * If you look carefully at Table 4 in this next study, you can see that naproxen (e.g., Naprosyn, Aleve) works for worse pain than ASA, as well as providing better pain relief for milder pain. 3. [Sindet-Pedersen S, Petersen JK, Go/tzsche PC, Christensen H. A double-blind, randomized study of naproxen and acetylsalicylic acid after surgical removal of impacted lower third molars. Int J Oral Maxillofac Surg 1986;15:389-94.] ------------------------------------------------------------------- * Next, you can confirm ibuprofen is superior for surgical pain, too. 5. [Slavic-Svircev V, Heidrich G, Kaiko RF, Rusy BF. Ibuprofen in the treatment of postoperative pain. Am J Med 1984; July 13:84-6] (This one also rated 400 mg ibuprofen better and longer than one acetaminophen + codeine tablet.) ------------------------------------------------------------------- * and headache: 6. [Diamond S. Ibuprofen versus aspirin and placebo in the treatment of muscle contraction headache. Headache 1983;23:206-10.] ------------------------------------------------------------------- * There is a direct trial that showed that naproxen was about the same as acetaminophen + codeine for surgical pain: 7. [Oullette RD, Feinberg A, Laraga R, Rothernberg RE, Welch GW. Naproxen sodium vs acetaminophen plus codeine in postsurgical pain. Curr Ther Res 1986;39(5):839-845.] ------------------------------------------------------------------- So the logical arguments go like this: Argument 1: acetaminophen = aspirin [2] naproxen > aspirin [4] ibuprofen = naproxen (I'll not cite any evidence, but if you think it's stronger you'll have to cite some evidence to prove it!) therefore, ibuprofen > acetaminophen Argument 2: acetaminophen = aspirin [2], and ibuprofen > aspirin [5,6] therefore, ibuprofen > acetaminophen Argument 3: naproxen = acetaminophen + codeine [7] acetaminophen + codeine > acetaminophen [2] ------------------------------------------------------------------- Finally, there were direct trials of ibuprofen vs acetaminophen. Still unbeaten is the champ, ibuprofen! 8. [Cooper SA. Five studies on ibuprofen for postsurgical dental pain. Am J Med 1984; July 13:70-7.] ------------------------------------------------------------------- Q.E.D. NAPROXEN SODIUM VERSUS ACETAMINOPHEN-CODEINE FOR PAIN FOLLOWING PLASTIC SURGERY Vargas Busquets, M.A., et al, Curr Ther Res 43(2):311, February 1988 Naproxen sodium has been shown to be an effective analgesic in a variety of patients with postoperative pain. This random, double-blind, multicenter study compared the efficacy of naproxen sodium and acetaminophen plus codeine in 91 patients with moderate to moderately severe pain following plastic surgery procedures. In the first day following surgery, the patients were treated with either two 275mg naproxen capsules or two 300mg acetaminophen plus 30mg codeine capsules. Patients requesting additional analgesics four hours after initial dosing were treated with one naproxen or acetaminophen plus codeine capsule. Significant pain relief was provided by both treatment regimens. There were no significant differences between the two regimens in pain relief parameters during the six-hour study period. Adverse effects were reported by 12% of the patients treated with naproxen and by 23% of those treated with acetaminophen plus codeine. No patient required discontinuation of the study drug. A second dose of analgesic during the study period was required by more patients taking acetaminophen plus codeine (31% vs. 23%). These findings indicate that naproxen sodium appears to be as effective as acetaminophen plus codeine in relieving moderate to moderately severe pain following plastic surgery but produces fewer side effects. The data provide further evidence that use of narcotic agents for control of postoperative pain may be unnecessary. NAPROXEN SODIUM VS. ACETAMINOPHEN PLUS CODEINE IN POSTSURGICAL PAIN Ouellette, R.D., et al, Curr Ther Res 39(5):839, May 1986 This random, double-blind, multicenter study compared the efficacy of naproxen sodium and acetaminophen plus codeine in 109 adult patients having abdominal surgical procedures. The incisions were relatively small in 72% of the patients. Following surgery, the patients were treated with 550mg naproxen sodium (56) or 600mg acetaminophen plus 60mg codeine (53). Additional half strength doses were available every four to six hours if necessary. Pain intensity was assessed serially for six hours after the initial dose. By four hours, an additional dose was required by only one patient. Forty-eight percent of the patients in the naproxen sodium group and 42% of those in the acetaminophen plus codeine group required only a single dose of the study medication throughout the six-hour study period. Analysis of Pain Intensity Difference scores and Summed Pain Intensity Difference revealed no significant differences between the two groups, although a trend was observed in favor of naproxen sodium. Analysis of tolerability in 118 patients revealed no significant differences between the two groups in the prevalence of adverse side effects, which were reported in six patients taking naproxen sodium and nine of those taking acetaminophen plus codeine. Gastrointestinal complaints prompted discontinuation of treatment in two patients taking naproxen sodium and three of those taking acetaminophen plus codeine. It is concluded that the efficacy and tolerability of naproxen sodium in patients with an following abdominal surgery is comparable to that of acetaminophen plus codeine in the doses evaluated, and that administration of naproxen sodium avoids the disadvantages of use of narcotics. TREATMENT OF MILD TO MODERATE PAIN OF ACUTE SOFT TISSUE INJURY: DIFLUNISAL VS ACETAMINOPHEN WITH CODEINE Muncie, H.L., et al, J Fam Pract 23(2):125, August 1986 This random, prospective study, from the University of Maryland School of Medicine, compared the response to the nonsteroidal antiinflammatory agent diflunisal (DolobidR,MSD) and to acetaminophen plus codeine in 35 patients with mild to moderate pain due to acute soft tissue injuries. The back was the most common site of injury, and muscle strain was the most common type of injury. Eighteen patients were treated with diflunisal (1000mg initially followed by 500mg every twelve hours), and 17 comparable patients were treated with acetaminophen plus codeine (650mg and 60mg, respectively, one or two tablets every four to six hours) until they became pain free, experienced intolerable side effects, or had been treated for a maximum of seven days. Pain and limitation of function scores, assessed on a scale of 0-4, decreased from 3.3 at baseline to 1.3, and from 3.1 to 1.5, respectively, in the diflunisal group, and from 3.3 to 1.6 and 2.9 to 1.9, respectively, in the acetaminophen plus codeine group. In patients requiring a full seven-day treatment course, greater differences were observed between the two treatment groups. Pain scores decreased from 3.5 to 2.3 in the acetaminophen plus codeine group, and from 3.0 to 1.5 in the diflunisal group; limitation of function scores decreased from 3.2 to 3.0 in the acetaminophen plus codeine group, and from 3.2 to 1.7 in the diflunisal group. At least one side effect was reported in 65% of the patients taking acetaminophen plus codeine, compared to 28% of those taking diflunisal (p=0.06). Intolerable side effects prompted discontinuation of acetaminophen plus codeine by 35% of the patients. Diflunisal appeared to be as effective as, and somewhat more tolerated than, acetaminophen plus codeine in the patients studied. COMPARISON OF DIFLUNISAL AND ACETAMINOPHEN WITH CODEINE IN THE TREATMENT OF INITIAL OR RECURRENT ACUTE LOW BACK STRAIN Brown, F.L., et al, Clin Ther 9(Suppl C):52, 1986 The authors, from the University of Maryland Health Center, conducted a random, prospective clinical study to compare the effects of diflunisal (Dolobid), a peripherally acting nonsteroidal antiinflammatory, and acetaminophen plus codeine in 40 ambulatory adults presenting with an initial episode or recurrence of acute low back strain. Nineteen patients received diflunisal (1000 mg followed by 500mg every twelve hours) and 21 received acetaminophen plus codeine (600mg and 60mg, respectively, followed by 300mg and 30mg, respectively, every four hours). The patients were treated for fifteen days, or less if pain had resolved before that time. All of the patients taking diflunisal who continued treatment beyond seven days were pain free after day twelve. Diflunisal was rated as good or excellent by 47% of the patients, and as poor by 11% (two patients). Treatment with acetaminophen plus codeine was associated with pain relief by day twelve, followed by a return of mild pain on days 12-15. Acetaminophen plus codeine treatment was rated as good or excellent by 43% of the patients, and as poor by 5% (one patient). Functional recovery in both groups was comparable. Sixteen percent of the patients taking diflunisal (three) each reported one adverse side effect, while ten side effects were reported by 24% of the patients taking acetaminophen plus codeine (five). It is concluded that the efficacy of diflunisal and acetaminophen plus codeine is comparable in patients with acute low back strain. The advantages of diflunisal include a relative lack of side effects and a twice daily dosing regimen. COMPARISON OF DIFLUNISAL AND ACETAMINOPHEN WITH CODEINE IN THE TREATMENT OF MILD TO MODERATE PAIN DUE TO STRAINS AND SPRAINS Indelicato, PA., Clin Ther 8(3):269, 1986 This random, prospective study, from the University of Florida, compared the efficacy of diflunisal, a long acting peripherally acting nonnarcotic, nonsteroidal anti-inflammatory agent with analgesic properties, and acetaminophen with codeine in 50 young athletes with mild to moderate sprains or strains. The patients were treated with either diflunisal (DolobidR, MSD), lgm followed by 500mg every twelve hours, or acetaminophen (300mg or 600mg) with codeine (30mg or 60mg) every four to six hours. Analysis of the patients' daily assessments and the results of reevaluation by the clinicians three, five, and seven days after initiation of treatment indicated that pain was markedly relieved by day five in both treatment groups, and that both groups demonstrated comparable improvement in pain, swelling, and tenderness. The average duration of therapy with diflunisal and acetaminophen plus codeine was 8.3 days and 7.5 days, respectively. Side effects consisted of a rash which developed after an initial dose of diflunisal prompting discontinuation of treatment. Good to excellent results were reported in 88% of the patients taking diflunisal and 80% of those taking acetaminophen with codeine. It is concluded that the effects of diflunisal are comparable to those of acetaminophen with codeine in young athletes sustaining mild to moderate strains or sprains, and that diflunisal is well tolerated and requires less frequent dosing.