Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies. Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. A randomised clinical trial of the effect of informed consent on the analgesic activity of placebo and naproxen in cancer pain. Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee. Medical therapy of malignant nerve pain. A randomised double-blind explanatory trial with naproxen versus slow-release morphine. Danazol and medroxyprogesterone acetate inefficacious in the treatment of infertility in endometriosis. Additive effect of combined naproxen and paracetamol in rheumatoid arthritis. Efficacy and tolerability of the specific cyclooxygenase-2 inhibitor DFP compared with naproxen sodium in patients with postoperative dental pain.
A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient. Dysmenorrhea is the most common menstrual complaint in young women, with a prevalence as high as 90%. It is responsible for substantial repeated short-term absenteeism from school and work in young women. Effective treatments are available, including nonsteroidal anti-inflammatory drugs (NSAIDs). In many countries, a variety of NSAIDs have become available as over-the-counter (OTC) drugs.
                The goal of this study was to compare the efficacy and safety of OTC doses of naproxen (400 mg) and naproxen/naproxen sodium (200/220 mg) with acetaminophen (1000 mg), ibuprofen (200 mg), and placebo in the treatment of primary dysmenorrhea.
                A pooled analysis of 5 trials was performed. Efficacy was assessed by pain relief, relief of other dysmenorrheic symptoms, time to backup medication or remedication, and treatment preference. Tolerability was assessed by recording adverse events (AEs).
                A total of 443 women were enrolled in the combined studies. Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration (P < 0.01 and P < 0.05, respectively). Furthermore, naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen (P < 0.01 and P < 0.05, respectively) and ibuprofen (P < 0.001 and P < 0.01, respectively) at 6 hours after administration. Both doses of naproxen had higher scores than placebo for symptom relief and drug preference (all P < 0.001). The AEs and their frequency were similar among the treatment groups. No serious AEs were reported.
                When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied. To demonstrate that in patients receiving naproxen for the pain of osteoarthritis (OA), the addition of tramadol will allow a reduction in the naproxen dosage without compromising pain relief.
                This trial consisted of a 5-week open-label run-in and an 8-week double-blind phase. Patients with at least moderate pain (> or =40 mm on a 100-mm visual analog scale) of OA of the knee after a 1-week medication washout were treated with naproxen 500 mg/day for 1 week. Patients whose pain scores were reduced to <20 mm were discontinued. The remaining patients received naproxen 1,000 mg/day for 3 weeks. Tramadol 200 mg/day was added during the third week. Patients were then randomized in a double-blind manner to continue tramadol 200 mg/day or to begin placebo in addition to naproxen. Randomization was stratified based on response to naproxen 1,000 mg/day. During the double-blind phase, the naproxen dose was reduced by 250 mg every 2 weeks. The primary efficacy end point was the minimum effective naproxen dose (MEND). The MEND was defined as 250 mg above the naproxen daily dosage at which pain relief was no longer adequate. Patients discontinuing the double-blind phase of the study for reasons other than lack of efficacy were assigned a MEND equal to the last naproxen dose received. If the effect of treatment between the responder and nonresponder groups was statistically different, the difference in the MEND was assessed separately within the groups.
                Of 236 patients randomized (mean age 61 years; 147 females), 90 were stratified as naproxen responders and 146 as naproxen nonresponders. There was a significant difference (P = 0.040) in the treatment effect between the naproxen responders and nonresponders, thus demonstrating a difference in the way responders and nonresponders react to a decrease in naproxen dosage after the addition of tramadol. Among naproxen responders, the MEND was significantly lower in patients receiving tramadol (n = 36) than in patients receiving placebo (n = 54), 221 mg versus 407 mg, respectively (P = 0.021). For the naproxen nonresponders, the mean MEND was 419 mg in the tramadol group and 396 mg in the placebo group (P = 0.706).
                In patients with painful OA of the knee responding to naproxen 1,000 mg/day, the addition of tramadol 200 mg/day allows a significant reduction in the dosage of naproxen without compromising pain relief. To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo, we conducted a prospective, randomised, single dose, placebo-controlled trial. Patients were randomly selected to receive or not information concerning the study. All patients included were then given a single dose of naproxen and placebo according to a crossover, double-blind design. Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study. Twenty-five received both treatments without any information and constituted the uninformed group. Twenty-four had a complete information about the trial; six refused to participate. The 18 others constituted the informed-consent group. Visual analogue scales of pain before and 30, 60, 120 and 180 min after the intake of naproxen and placebo were recorded. As an analgesic, naproxen was more effective than placebo in both groups of patients (p = 0.001). For naproxen as well as for placebo, the analgesic effect was better in the informed-consent group compared to the uninformed group (p = 0.012). The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients (p = 0.08). We concluded that, in contrast with parallel studies, giving information in a crossover, placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo, and decrease the perceived difference the two. To compare the relative safety and efficacy of naproxen and acetaminophen in the treatment of osteoarthritis (OA) of the knee. The major outcome measures were radiographic progression and withdrawal from the trial due to lack of efficacy.
                One hundred seventy-eight patients with OA of the knee were enrolled in a 2-year prospective, controlled, double-blind multicenter trial and were randomly assigned to receive acetaminophen (ACT) or naproxen (NPX) treatment.
                After 6 weeks of treatment, modest improvement in pain on motion and in physician's global assessment was seen in both the ACT and the NPX groups, and the NPX group also had modest improvement in pain at rest and in 50-foot walk time. Sixty-two patients completed the 2-year study. Among these patients, radiographic progression was similar in the 2 treatment groups. Withdrawal from the trial due to lack of drug efficacy was slightly more frequent among patients in the ACT group (22% versus 16%), but withdrawal due to adverse drug effects was slightly more common in the NPX group (23% versus 18%).
                The efficacy of ACT treatment and NPX treatment was similar, although it was slightly better for NPX. The toxicity rate was slightly lower with ACT. However, the high rate of withdrawal in both treatment groups suggests that neither is satisfactory for the treatment of OA. It is uncertain whether there exists a nociceptive component in malignant nerve pain responsive to NSAIDs and opioids. 20 patients with malignant nerve pain were randomly assigned to treatment with naproxen 1500 mg versus slow-release morphine 60 mg daily during 1 week, followed by cross-over medication during the second week in a double-blind, double-dummy protocol. In the 16 evaluable patients, a significant (P < 0.05) reduction of 26% (S.E. +/- 7.9) in pain intensity was reached at day 7, compared to baseline pain. At day 7, significant pain relief of 32% (P < 0.05) was observed in the naproxen group, but not in the morphine group (21%, P = 0.14). Patients using morphine needed approximately twice as much paracetamol rescue than patients using naproxen. Additional pain relief could be observed in 4/9 patients with cross-over medication. These data support the concept of a nociceptive component in malignant nerve pain responding to NSAIDs and opioids, and favour the combination of both an anti-inflammatory drug and an opioid for symptomatic pain relief. Danazol (200 mg three times a day) and medroxyprogesterone acetate (MPA, 100 mg a day) were compared with placebo in the treatment of infertility of patients with endometriosis. Twenty-seven patients had medical therapy alone for 6 months, and 22 patients received it after conservative surgery. The clinical characteristics of the patients in the danazol group (n = 18), the MPA group (n = 17), and the placebo group (n = 14) were comparable to each other. The follow-up time was 30 months. The cumulative pregnancy rates, 33% in the danazol group (n = 6), 42% in the MPA group (n = 7), and 46% in the placebo group (n = 6), did not differ significantly from each other. The time to pregnancy after the start of therapy was 17.7 +/- 8.4 (standard deviation [SD]) months in the danazol group, 18.0 +/- 9.0 months in the MPA group and 10.0 +/- 5.8 months in the placebo group with no significant difference between the groups. The abortion rate was 26%, and there was no significant difference among the groups. Cox multivariant analysis did reveal ovarian endometriosis a prognostically significant negative indicator as regards fecundation in endometriosis (P less than 0.05). In summary, correction of infertility alone does not appear to be an indication for the use of danazol or MPA in the treatment of endometriosis, and ovarian endometriotic lesions but not peritoneal ones do make a worse prognosis as regards fecundation in endometriosis. The clinical effect and plasma naproxen levels were studied in 20 patients with RA receiving three doses of naproxen and two naproxen doses combined with paracetamol (acetaminophen) in a randomized, double-blind, comparison in five 2-wk treatment periods. A significant dose-concentration effect relationship was found for the three naproxen doses (500, 1000 and 1500 mg daily). The following variables were measured: global clinical effect, joint index, morning stiffness, activity of daily living (ADL), pain during movement and at rest. The naproxen dose-concentration effect relationship curve was moved to the left by the addition of 4 g paracetamol daily. No major side effects were observed, but complaints concerning the gastrointestinal tract were fewer on lower naproxen doses and these were not increased by concomitant paracetamol treatment. The results show that the clinical effect of naproxen in RA may be significantly increased by concomitant paracetamol administration. DFP [3-(2-propyloxy)-(4-methyl-sulfonylphenyl)-(5,5-dimethyl)-fu ranone] is a highly specific cyclooxygenase-2 inhibitor (>2500-fold selective in transfected Chinese hamster ovary cell assays) that has demonstrated efficacy in preclinical models of pain and inflammation. The present single-dose, randomized, double-masked, double-dummy, placebo-controlled, parallel-group study was undertaken to compare DFP 5, 25, and 50 mg with naproxen sodium 550 mg and with placebo in 196 patients (mean age, 25.8 years; 187 [95.4%] males) who experienced moderate-to-severe pain after surgical removal of > or =2 third molars. Overall analgesic effect, duration of effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. Both DFP 25 and 50 mg, as well as the active comparator, naproxen sodium 550 mg, were significantly more effective than placebo. The onset of analgesic effect in the DFP 25-mg, DFP 50-mg, and naproxen sodium 550-mg groups did not differ significantly. DFP was generally well tolerated in single doses up to 50 mg. DFP 50 mg was efficacious in the treatment of postoperative dental pain and was indistinguishable from the active comparator, naproxen sodium 550 mg.
One small study found no significant difference between groups treated with OCP, mefenamic acid, low dose danazol or naproxen. Overall, the evidence from the one study is not sufficient to adequately assess the effectiveness of OCP. 
This review was unable to achieve its stated objectives because of the paucity of the data.