Physician Global Ratings Research Articles

The antipruritic effect of 5% doxepin cream in patients with eczematous dermatitis. Doxepin Study Group

Eczematous dermatitis is commonly characterized by intense pruritus. Current treatment modalities for this condition, regardless of its cause, are primarily directed at blunting the cutaneous inflammatory response and thereby providing relief of pruritus. To expand on our previous findings in atopic dermatitis, the present multicenter double-blind trial was conducted to evaluate the safety and antipruritic efficacy of 5% doxepin hydrochloride cream in patients with lichen simplex chronicus (n = 136), nummular eczema (n = 87), or contact dermatitis (n = 86). A total of 309 patients with moderate to severe pruritus were randomly assigned to apply either doxepin cream (n = 154) or vehicle cream (n = 155) to eczematous areas four times per day for a period of 7 days. Efficacy was assessed using a pruritus severity rating scale, a Physician's Global Evaluation for pruritus relief, and a Visual Analogue Scale for pruritus relief. Twenty-four hours after initiation of treatment, and continuing throughout the remainder of the study, patients treated with doxepin cream experienced significantly greater pruritus relief than did vehicle-treated patients as determined by all efficacy parameters (P < .002). Sixty percent of doxepin-treated patients experienced pruritus relief within 24 hours. The response rate increased to 84% by conclusion of the study. As judged by significant changes (P < or = .05) occurring in at least one assessment of efficacy, doxepin cream provided pruritus relief in all forms of eczematous dermatitis that were examined. The study medication was well tolerated. The two most common adverse effects, stinging at the site of application and drowsiness, were usually transient and mild to moderate in severity. Topical application of doxepin provides significant antipruritic activity with a favorable safety profile, suggesting a role for doxepin cream in the symptomatic treatment of pruritus associated with eczematous dermatitis.

The Antipruritic Effect of 5% Doxepin Cream in Patients With Eczematous Dermatitis

Eczematous dermatitis is commonly characterized by intense pruritus. Current treatment modalities for this condition, regardless of its cause, are primarily directed at blunting the cutaneous inflammatory response and thereby providing relief of pruritus. To expand on our previous findings in atopic dermatitis, the present multicenter double-blind trial was conducted to evaluate the safety and antipruritic efficacy of 5% doxepin hydrochloride cream in patients with lichen simplex chronicus (n = 136), nummular eczema (n = 87), or contact dermatitis (n = 86). A total of 309 patients with moderate to severe pruritus were randomly assigned to apply either doxepin cream (n = 154) or vehicle cream (n = 155) to eczematous areas four times per day for a period of 7 days. Efficacy was assessed using a pruritus severity rating scale, a Physician's Global Evaluation for pruritus relief, and a Visual Analogue Scale for pruritus relief.Twenty-four hours after initiation of treatment, and continuing throughout the remainder of the study, patients treated with doxepin cream experienced significantly greater pruritus relief than did vehicle-treated patients as determined by all efficacy parameters (P < .002). Sixty percent of doxepin-treated patients experienced pruritus relief within 24 hours. The response rate increased to 84% by conclusion of the study. As judged by significant changes (P < or = .05) occurring in at least one assessment of efficacy, doxepin cream provided pruritus relief in all forms of eczematous dermatitis that were examined. The study medication was well tolerated. The two most common adverse effects, stinging at the site of application and drowsiness, were usually transient and mild to moderate in severity.Topical application of doxepin provides significant antipruritic activity with a favorable safety profile, suggesting a role for doxepin cream in the symptomatic treatment of pruritus associated with eczematous dermatitis.

TOPICAL NICOTINAMIDE COMPARED WITH CLINDAMYCIN GEL IN THE TREATMENT OF INELAMMATORY ACNE VULGARIS

Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance. In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks. Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating. After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. Both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, nicotinamide vs. -43%, clindamycin, P = 0.168), and acne severity (-52% nicotinamide group vs. -38% clindamycin group, P = 0.161). These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.

Comparison of intranasal triamcinolone acetonide with oral loratadine for the treatment of patients with seasonal allergic rhinitis

This multicenter, double-blind, randomized, controlled, parallel-group study compared the safety and efficacy of intranasal triamcinolone acetonide with oral loratadine in relieving symptoms of ragweed-induced seasonal allergic rhinitis. Patients from community-based allergy practices with a history of at least two seasons of seasonal allergic rhinitis verified by a positive skin test received either once-daily treatment with intranasal triamcinolone acetonide 220 μg plus 1 placebo capsule or oral loratadine 10 mg plus placebo nasal spray. Other medications for rhinitis were prohibited. Changes in rhinitis symptoms were assessed by using patient evaluations, physician global evaluations, and withdrawal rates. Efficacy was evaluated in 274 of 298 patients randomized to treatment (134 to triamcinolone acetonide and 140 to loratadine). Mean total nasal symptom scores for weeks 1, 2, 3, and 4 and the overall score showed greater improvement ( P = 0.001) with triamcinolone acetonide than with loratadine. Improvement in all rhinitis symptoms was significantly greater with triamcinolone acetonide than with loratadine; there was a trend for greater improvement in ocular symptoms with triamcinolone acetonide. Physicians' global evaluations indicated triamcinolone acetonide provided moderate-to-complete relief in 78% of patients compared with 58% of loratadine-treated patients ( P ≤ 0.0001). Both treatments were well tolerated; headache was the most commonly reported adverse event in both groups. Intranasal triamcinolone acetonide was significantly more effective than oral loratadine in relieving the symptoms of seasonal allergic rhinitis.

Long-term treatment of perennial allergic rhinitis with ipratropium bromide nasal spray 0.06%

The purpose of this study was to assess the safety and efficacy of ipratropium bromide nasal spray 0.06% (aqueous solution), 84 μg per nostril three times a day, in reducing nasal hypersecretion in the long-term treatment of patients with perennial allergic rhinitis (PAR). This was an open-label 1-year trial. In the first 6 months all patients were treated with two puffs ipratropium bromide nasal spray 0.06%, 84 μg per nostril three times per day, unless they were unable to tolerate the dose. In the last 6 months the dose could be reduced to the lowest amount required to control rhinorrhea. Ninety-six patients entered the trial, and 47 completed it. Sixty-three patients completed more than 6 months of treatment. Patient and physician global evaluation suggested that ipratropium bromide nasal spray 0.06% is effective in controlling rhinorrhea associated with PAR and can contribute to control of congestion, postnasal drip, and sneezing. There was also a trend toward reduction of mucosal edema and improvement in quality of life. The most common drug-related adverse events were nasal dryness, epistaxis/nose bleed, and increased rhinitis. Most adverse events were mild and resulted in drug discontinuation in less than 10% of patients. Ipratropium bromide nasal spray was well tolerated and not associated with serious drug-related adverse events or clinically significant anticholinergic side effects. Use of ipratropium bromide nasal spray alone or with other standard medications should be considered in treating patients with PAR. (J A LLERGY C LIN I MMUNOL 1995;95:1128-32.)

Safety and Efficacy of Diclofenac Sodium 0.1% Ophthalmic Solution in Acute Seasonal Allergic Conjunctivitis

A randomized clinical trial was conducted to compare diclofenac sodium 0.1% ophthalmic solution to placebo in relieving ocular signs and symptoms in patients with acute seasonal allergic conjunctivitis. Twenty patients (10 per treatment) qualified for this two week, double-masked study with moderate itching, bulbar conjunctival injection and a positive skin test. Diclofenac was statistically and clinically superior in the physician's global evaluation (p = 0.03) and the primary composite score [itching + bulbar/palpebral conjunctival injection (p = 0.037)] after two weeks of treatment. Four patients experienced some transient ocular burning/stinging with diclofenac. Diclofenac sodium appears to be effective for relieving the ocular signs and symptoms associated with acute seasonal allergic conjunctivitis.

Capsaicin cream 0.025% as Monotherapy for Osteoarthritis: A double-blind study

The efficacy and safety of 0.025% capsaicin cream were evaluated when it was used as the only symptomatic therapy in patients with osteoarthritis (OA) pain. Patients (113) received either topical capsaicin or vehicle four times daily in this 12-week, double-blind, randomized, vehicle-controlled, multicenter study. Capsaicin was superior to vehicle in providing pain relief. At the end of the study, more patients on capsaicin (81 %) than vehicle (54%) were improved by physician's global evaluation ( P = .03). Similar results were obtained by patient's global evaluation. Capsaicin-treated patients reported greater reduction of pain on the visual analog scale (VAS) at week 4 ( P = .01), week 8 ( P = .01), and week 12 ( P = .02). Capsaicin -treated patients also had greater reduction in pain on passive range of motion by week 8 ( P = .03) that was sustained through week 12 ( P = .03). Joint tenderness evaluated by palpation declined in capsaicin-treated patients at week 4 ( P = .03), week 8 ( P = .01 ), and week 12 ( P = .01 ). Adverse effects attributable to capsaicin were mild to moderate burning and stinging at the application site (46% of patients). The burning resolved in most patients; only 3 (7%) patients experienced burning at week 12. These results support the beneficial effects of 0.025% capsaicin cream as a first-line therapy for OA pain.

A double-blind evaluation of topical capsaicin in pruritic psoriasis

Substance P, an undecapeptide neurotransmitter, has been implicated in the pathophysiology of psoriasis and pruritus. Safety and efficacy of topical capsaicin, a potent substance P depletor, were evaluated in patients with pruritic psoriasis. Patients applied capsaicin 0.025% cream (n = 98) or vehicle (n = 99) four times a day for 6 weeks in this double-blind study. Efficacy was based on a physician's global evaluation and a combined psoriasis severity score including scaling, thickness, erythema, and pruritus. Capsaicin-treated patients demonstrated significantly greater improvement in global evaluation (p = 0.024 after 4 weeks and p = 0.030 after 6 weeks) and in pruritus relief (p = 0.002 and p = 0.060, respectively), as well as a significantly greater reduction in combined psoriasis severity scores (p = 0.030 and p = 0.036, respectively). The most frequently reported side effect in both treatment groups was a transient burning sensation at application sites. Topically applied capsaicin effectively treats pruritic psoriasis, a finding that supports a role for substance P in this disorder.

Meta-analysis of second-line antirheumatic drugs: sample size bias and uncertain benefit

Placebo controlled trials of methotrexate, auranofin, penicillamine, azathioprine, sulphasalazine, gold sodium thiomalate and chloroquines were subjected to meta-analysis. The difference between drugs and placebo in the erythrocyte sedimentation rate was 8.8 mm/hr [95% confidence interval (CI), 6.4–11.3]. In multiple linear regression analyses, with the physician's global evaluation and relative change in joint tenderness count as outcome variables, a substantial sample size bias was demonstrated. The effect decreased with increasing sample size. The risk of dropping out from any cause was larger on drug than on placebo (odds ratio, 1.17; CI, 0.99–1.38). No evidence of a worthwhile effect on radiological changes was found. Of the 3439 patients, 4 went into complete remission on drug. We conclude that the benefit of second-line drugs is uncertain.

Topical Capsaicin in Painful Diabetic Neuropathy: Controlled Study With Long-Term Follow-Up

We conducted an 8-wk controlled study with topical 0.075% capsaicin in subjects with chronic severe painful diabetic neuropathy who were unresponsive or intolerant to conventional therapy. Capsaicin is an alkaloid found in capsicum peppers and produces desensitization to noxious thermal, chemical, and mechanical stimuli when applied topically. In 22 randomly assigned subjects, either capsaicin or vehicle cream was applied to painful areas 4 times/day. Pain measurements were recorded at baseline and at 2-wk intervals for 8 wk. Capsaicin treatment was more beneficial than vehicle treatment in the overall clinical improvement of pain status, as measured by physician's global evaluation (P = 0.038) and by a categorical pain severity scale (P = 0.057). Decrease in mean pain intensity by a visual analogue scale was 16% in capsaicin-treated and 4.1% in vehicle-treated subjects. Mean pain relief on visual analogue scale was 44.6 and 23.2%, respectively. In a follow-up open-label study, approximately 50% of subjects reported improved pain control or were cured, and 25% each were unchanged or worse. A burning sensation at the application site was noted by some subjects but both its magnitude and duration decreased with time. Results from this preliminary study suggest that topical 0.075% capsaicin may be of value in subjects with diabetic neuropathy and intractable pain.

The symptom checklist-90: Obsessive-compulsive subscale: A reliability and validity study

Twenty-three, nondepressed patients with DSM-III obsessive-compulsive disorder completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Symptom Checklist-90 (SCL-90), and the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-GOCS) once a week for a total of three times during a 2-week medication-free period and 10 times during a 10-week double-blind drug treatment period. The pretreatment test-retest reliabilities were determined for the Y-BOCS, NIMH-GOCS, and the SCL-90-Obsessive-Compulsive Subscale (SCL-90-OCS). Comparisons of the three instruments revealed that the Y-BOCS and the NIMH-GOCS were significantly more reliable than the SCL-90-OCS. Posttreatment correlations were obtained between change scores on the Y-BOCS and NIMH-GOCS and the SCL-90-OCS. Correlations were high and statistically significant for both the Y-BOCS and the NIMH-GOCS, but the correlations of the SCL-90-OCS with the Y-BOCS, NIMH-GOCS, Physician's Global Rating, and the Patient's Global Rating were poor. The findings suggest that the SCL-90-OCS may not be a sensitive instrument in assessing change in obsessive-compulsive symptoms.

Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: Report on two double-blind, vehicle-controlled studies

The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double-blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel-group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for "effectiveness" and "overall rating" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of "stings" or "burns" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between enantiomer levels of flurbiprofen and clinical response in rheumatoid arthritis

The pharmacokinetics of flurbiprofen (ANSAID™) was evaluated in 25 patients with rheumatoid arthritis following an NSAID-free washout period. Statistically significant improvements were noted in pain, patient and physician global rating, Ritchie articular index, walk time, bead intubation coordinometry and zeta sedimentation rate. However, no statistically significant correlation was noted between these outcome measures and the primary pharmacokinetic parameters for S(+)-flurbiprofen (total plasma clearance, average steady state concentration, overnight trough plasma concentration). We conclude that the variability in the response to flurbiprofen cannot be accounted for on the basis of variability in the active drug concentrations in plasma for this racemic anti-inflammatory analgesic compound.

Double-blind comparison of etodolac and piroxicam in patients with rheumatoid arthritis

A study was carried out to compare the efficacy and tolerability of etodolac and piroxicam in patients with rheumatoid arthritis. Sixty patients entered this double-blind, parallel study and after a wash-out period of up to 2 weeks were randomly assigned to receive 200 mg etodolac twice daily or 20 mg piroxicam once daily for 12 weeks. Efficacy and tolerability assessments were made after 2, 4, 6, 8 and 12 weeks. Patients in the etodolac group demonstrated statistically significant improvement in the number of tender joints and the duration of morning stiffness after 12 weeks, as did the piroxicam-treated patients. In addition, the etodolac-treated patients had significant improvement according to the patients' and physician's global evaluations, pain intensity, number of swollen joints, and grip strength. There were significant differences between therapies favouring etodolac for the assessments of the number of tender joints and the physician's global evaluation by the end of the study. Forty-seven percent (47%) of 15 etodolac-treated patients compared with 7% of 15 piroxicam-treated patients showed improvement according to the physician's global evaluation at Week 12. Similarly, the patients' global evaluation showed that 40% of etodolac-treated patients and 19% of piroxicam-treated patients had improved by the end of therapy. Both therapies were well tolerated. There were no significant differences between groups in the incidence of any adverse reactions or the frequency of withdrawals.

The Yale-Brown obsessive-compulsive scale: A reliability and validity study

Twenty-eight nondepressed patients with DSM-III obsessive-compulsive disorder completed both the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Leyton Obsessional Inventory (LOI) once a week for a total of three times change. In general, the correlations between the Y-BOCS change scores and the Global Ratings were significantly greater than between the LOI and the Global scores, the Y-BOCS was found to be more reliable than the LOI. Correlations were also obtained for the baseline period between the Y-BOCS and Leyton scores. At the end of a 14-week trial of clomipramine, the Y-BOCS and the LOI were again administered along with a Physician and Patient Global Rating of change. In general, the correlations between the Y-BOCS change scores and the Global Ratings were significantly greater than between the LOI and the Global Ratings. This last finding suggests that the Y-BOCS is a better measure of clinical change than is the LOI.

Patterns of response during placebo treatment of panic disorder

Data from the cross-national study of panic disorder are used for an analysis of response patterns. The main purpose of the study is a search for specific placebo patterns and a discussion of possible differences in patterns from patients treated with alprazolam, imipramine, and placebo. Four outcome measures were registered at baseline and weekly during the treatment period: the number of panic attacks, Physician's Global Evaluation of treatment effect, the Overall Phobia Score and the level on the Hamilton Rating Scale for Anxiety. Response patterns from the 3 treatment groups are described and compared, and subsequently categorized with regard to completeness and persistency. No specific placebo pattern is recognized. Some differences are found, however, as many placebo patients demonstrate an early and temporary remission. The variations in response patterns do not compromise the blindness of the study, and their predictive validity is low.

A double-blind comparison of etodolac and piroxicam in the treatment of osteoarthritis

A double-blind study was carried out to compare the effectiveness and tolerability of two non-steroidal anti-inflammatory drugs, etodolac and piroxicam, in patients with osteoarthritis of the knee. Sixty-five patients with active, radiologically verified osteoarthritis were randomly assigned to receive either 300 mg etodolac twice a day (33 patients) or 20 mg piroxicam once a day (32 patients) for 8 weeks. Effectiveness was measured by changes in the patients' and physician's overall evaluations, pain intensity, and night pain, recorded on 5-point scales. Other efficacy assessments included tenderness on pressure, the degree of swelling, knee flexion, the time needed to walk 50 feet, and duration of morning stiffness. After 4 weeks of therapy, mean values for patients' and physician's global evaluations, pain intensity, and night pain were significantly improved from baseline values in both treatment groups. Improvement continued throughout the study. Significant improvement in the other efficacy assessments was seen in both treatment groups after 4 weeks of therapy. There were no significant differences between the treatment groups in any efficacy assessment at any observation. Three etodolac-treated patients and 2 piroxicam-treated patients withdrew from the study because of adverse events. The results of this study indicate that 600 mg etodolac per day is as effective as 20 mg piroxicam per day in the treatment of osteoarthritis.

Safety and Effectiveness of Cranial Electrotherapy in the Treatment of Tension Headache

One hundred patients were enrolled in a multicenter double-blind study to evaluate the safety and effectiveness of the Pain Suppressor Unit, a cranial electrotherapy stimulator for the symptomatic treatment of tension headaches. Treatment consisted of extremely low level, high frequency current applied transcranially. Pain scores before and after 20 minute treatments of individual headaches as well as patient and physician global evaluations were the primary efficacy variables. Following use of the active unit, patients reported an average reduction in pain intensity of approximately 35%. Placebo patients reported a reduction of approximately 18%. The difference was statistically significant (p = 0.01). The active unit was rated as moderately or highly effective in 40% by physicians, and in 36% by patients. Both physicians and patients scored the placebo unit moderately or highly effective for only 16%. The difference in ordered outcomes was statistically significant (p = 0.004). Approximately 10% of patients in each group reported at least one minor adverse experience. Cranial electrotherapy stimulation is distinct from TENS, and is safe and often effective in ameliorating the pain intensity of tension headaches. It should be considered as an alternative to the chronic usage of analgesics.

Methylprednisolone in cis-platinum induced nausea and emesis: A placebo-controlled trial

In a double-blind, placebo-controlled trial, the antiemetic efficacy of a total of 1–2 g methylprednisolone sodium succinate (MPSS) alone versus placebo was evaluated over the first three courses of chemotherapy in a group of 27 women receiving moderate to high-dose cis-platinum (50–118 mg/m2) for ovarian or cervical carcinomas. Antiemetic protection was classified as total (no emesis), major (one or two bouts), minor (three to five bouts), or minimal (six or more bouts). Total or major protection occurred in 1026 (38.5%) of the MPSS cycles and in 624 (25%) of the placebo cycles (NS). A significant number of placebo patients (714 placebo versus 113 MPSS, P = 0.02) dropped out of the study due to lack of efficacy. Patient evaluations completed 24 hr before and after each course of chemotherapy indicated no treatment effect on pain, appetite, nausea, drowsiness, anxiety, sense of well-being, or sleep. Physician and patient global evaluations of antiemetic efficacy favored treatment with MPSS. Evidence of the efficacy of single-drug MPSS antiemetic therapy during non-cis-platinum or low-dose cis-platinum (<50 mg/m2) chemotherapy can be found in the literature. The results of this study, however, do not support the use of MPSS alone with high-dose cis-platinum chemotherapy.

Proquazone for Tension Headache‐A Multicenter Trial

SYNOPSISThe efficacy and safety of proquazone 150 mg and proquazone 75 mg was compared to placebo in a double‐blind, randomized, parallel, multi‐investigator study in the acute treatment of muscle contraction (tension) headache.Of the 122 patients entered into the study, 5 were subsequently discontinued, and 117 patients (39 in each of the three treatment groups) were included in the efficacy analyses.The effects of proquazone 150 mg on all of the symptoms associated with the muscle contraction (tension) headache symptom complex, namely pain, psychic tension and muscle stiffness of the head, neck and shoulders, were significantly superior to both proquazone 75 mg and placebo. These results were consistent using both a patient self‐rating form and a physician's global evaluation of patient response to study medication. For the pain parameters, proquazone 75 mg also showed significant superiority to placebo indicating a dose related clinical effect of proquazone. Only four patients reported transient adverse effects after taking the study medication, which were considered to be mild in nature, and none required therapeutic intervention.