User login
What medications are safe and effective for heartburn during pregnancy?
Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy. (Grade of Recommendation: B [limited randomized controlled trials of short duration and small sample size])
Recommendations from others
Standard texts suggest that antacids1 or histamine (H2) blockers2 be used as first-line agents for reflux. Burrow and Duffyz3 recommend a stratified approach with antacids followed by H2-blockers, reserving the use of proton pump inhibitors for the more severe cases.
Evidence summary
Heartburn affects 30% to 50% of pregnancies and occurs primarily in the second and third trimesters.4 Lifestyle changes and dietary modification are recommended as initial measures for relief of symptoms.
Antacids
Each of the 3 identified placebo-controlled trials of antacid therapy had significant methodologic limitations. Aluminum phosphate more frequently produced complete relief of moderate to severe heartburn at 60 minutes compared with placebo (P <.001; number needed to treat [NNT] = 2.1 for mild heartburn and 20 for severe).5 Patients who received a combination of magnesium and aluminum hydroxide for 7 days had no more relief of symptoms than the placebo group.6 Atlay and colleagues7 found that sodium bicarbonate significantly reduced reflux symptoms compared with placebo (P=.021; NNT=6.0).
There are limited data regarding the safety of antacids during pregnancy. A single case-control study found a higher rate of congenital anomalies in children of women who took antacids in the first trimester (unadjusted odds ratio calculated from data=2.36; P <.05).8 This association was not detected when studied over the entire pregnancy. The rate of malformations was not different for magnesium, aluminum, and bicarbonate. The association could well be due to recall bias or other systematic biases inherent in case-control methodology.
H2-Blockers
The only identified studies of H2-blockers evaluated ranitidine. A 4-week double-blind randomized control trial found that ranitidine 150 mg twice daily reduced patient symptoms by 44% over placebo (P <.05).9 This study was limited by its short duration (<1 month) and small sample size (N=30). A 2-week study that compared antacids plus ranitidine to antacids alone found a 52% decrease in symptoms in the ranitidine group and a 44% reduction in the antacid-alone group.10 Ranitidine, cimetidine, and famotidine are US Food and Drug Administration (FDA) pregnancy category B (no demonstrated risk).
Proton Pump Inhibitors
In nonpregnant adults, proton pump inhibitors are more effective than antacids and H2-blockers for gastroesophageal reflux disease (GERD). No cohort or control studies have been performed on their efficacy in pregnancy. On the basis of animal studies, omeprazole is a category C drug (potential benefit of use should outweigh potential risks). A cohort study of 113 women found no associated anomalies (relative risk=1.94; 95% confidence interval, 0.36-10.36).11 Pantoprazole, lansoprazole and rabeprazole are category B medications.
Other Agents
Metoclopramide and sucralfate have been used in nonpregnant adults with GERD. Although both are category B, there are no data about their effectiveness for heartburn during pregnancy.
Donald N. Marquardt, PhD, MD
Iowa Health Physicians Cedar Rapids
Heartburn along with morning sickness and back pain frequently diminishes the joy of pregnancy. Simple nonpharmacologic solutions such as frequent small meals, remaining upright after eating, and elevating the head of the bed will often suffice. The traditional use of agents in their order of development (antacids, H2-blockers, then proton pump inhibitors) finds some justification in this review for selected agents. Particularly enlightening was the rationale for specific agents: aluminum phosphate has efficacy as an antacid; ranitidine is the only studied H2-blocker; and there are 3 FDA category B proton pump inhibitors (pantoprazole, lansoprazole, and rabeprazole). Specific recommendations for these agents would improve patient benefit with a minimum of therapeutic trials frustrating both patient and physician.
1. Gabbe SG, Niebyl JR, Simpson JL, Annas GJ, eds. Obstetrics: normal and problem pregnancies. 3rd ed. New York, NY: Churchill Livingstone; 1996.
2. Cunningham FG, Whitridge WJ. Williams obstetrics. 19th ed. Norwalk, Conn: Appleton & Lange; 1993.
3. Burrow GN, Duffy TP, eds. Medical complications during pregnancy. 5th ed. Philadelphia, Pa: WB Saunders; 1999.
4. Baron TH, Ramirez B, Richter JE. Gastrointestinal motility disorders during pregnancy. Ann Intern Med 1993;118:366-75.
5. Shaw RW. Randomized controlled trial of Syn-Ergel and an active placebo in the treatment of heartburn of pregnancy. J Int Med Res 1978;6:147-51.
6. Kovacs GT, Campbell J, Francis D, Hill D, Adena MA. Is mucaine an appropriate medication for the relief of heartburn during pregnancy?. Asia-Oceania J Obstet Gynaecol 1990;16:357-62.
7. Atlay RD, Weekes AR, Entwistle GD, Parkinson DJ. Treating heartburn in pregnancy: comparison of acid and alkali mixtures. BMJ 1978;2:919-20.
8. Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. BMJ 1971;1:523-27.
9. Larson JD, Patatanian E, Miner PB, Jr, Rayburn WF, Robinson MG. Double-blind, placebo-controlled study of ranitidine for gastroesophageal reflux symptoms during pregnancy. Obstet Gynecol 1997;90:83-87.
10. Rayburn W, Liles E, Christensen H, Robinson M. Antacids vs. antacids plus non-prescription ranitidine for heartburn during pregnancy. Int J Gynaecol Obstet 1999;66:35-37.
11. Lalkin A, Loebstein R, Addis A, et al. The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol 1998;179:727-30.
Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy. (Grade of Recommendation: B [limited randomized controlled trials of short duration and small sample size])
Recommendations from others
Standard texts suggest that antacids1 or histamine (H2) blockers2 be used as first-line agents for reflux. Burrow and Duffyz3 recommend a stratified approach with antacids followed by H2-blockers, reserving the use of proton pump inhibitors for the more severe cases.
Evidence summary
Heartburn affects 30% to 50% of pregnancies and occurs primarily in the second and third trimesters.4 Lifestyle changes and dietary modification are recommended as initial measures for relief of symptoms.
Antacids
Each of the 3 identified placebo-controlled trials of antacid therapy had significant methodologic limitations. Aluminum phosphate more frequently produced complete relief of moderate to severe heartburn at 60 minutes compared with placebo (P <.001; number needed to treat [NNT] = 2.1 for mild heartburn and 20 for severe).5 Patients who received a combination of magnesium and aluminum hydroxide for 7 days had no more relief of symptoms than the placebo group.6 Atlay and colleagues7 found that sodium bicarbonate significantly reduced reflux symptoms compared with placebo (P=.021; NNT=6.0).
There are limited data regarding the safety of antacids during pregnancy. A single case-control study found a higher rate of congenital anomalies in children of women who took antacids in the first trimester (unadjusted odds ratio calculated from data=2.36; P <.05).8 This association was not detected when studied over the entire pregnancy. The rate of malformations was not different for magnesium, aluminum, and bicarbonate. The association could well be due to recall bias or other systematic biases inherent in case-control methodology.
H2-Blockers
The only identified studies of H2-blockers evaluated ranitidine. A 4-week double-blind randomized control trial found that ranitidine 150 mg twice daily reduced patient symptoms by 44% over placebo (P <.05).9 This study was limited by its short duration (<1 month) and small sample size (N=30). A 2-week study that compared antacids plus ranitidine to antacids alone found a 52% decrease in symptoms in the ranitidine group and a 44% reduction in the antacid-alone group.10 Ranitidine, cimetidine, and famotidine are US Food and Drug Administration (FDA) pregnancy category B (no demonstrated risk).
Proton Pump Inhibitors
In nonpregnant adults, proton pump inhibitors are more effective than antacids and H2-blockers for gastroesophageal reflux disease (GERD). No cohort or control studies have been performed on their efficacy in pregnancy. On the basis of animal studies, omeprazole is a category C drug (potential benefit of use should outweigh potential risks). A cohort study of 113 women found no associated anomalies (relative risk=1.94; 95% confidence interval, 0.36-10.36).11 Pantoprazole, lansoprazole and rabeprazole are category B medications.
Other Agents
Metoclopramide and sucralfate have been used in nonpregnant adults with GERD. Although both are category B, there are no data about their effectiveness for heartburn during pregnancy.
Donald N. Marquardt, PhD, MD
Iowa Health Physicians Cedar Rapids
Heartburn along with morning sickness and back pain frequently diminishes the joy of pregnancy. Simple nonpharmacologic solutions such as frequent small meals, remaining upright after eating, and elevating the head of the bed will often suffice. The traditional use of agents in their order of development (antacids, H2-blockers, then proton pump inhibitors) finds some justification in this review for selected agents. Particularly enlightening was the rationale for specific agents: aluminum phosphate has efficacy as an antacid; ranitidine is the only studied H2-blocker; and there are 3 FDA category B proton pump inhibitors (pantoprazole, lansoprazole, and rabeprazole). Specific recommendations for these agents would improve patient benefit with a minimum of therapeutic trials frustrating both patient and physician.
Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy. (Grade of Recommendation: B [limited randomized controlled trials of short duration and small sample size])
Recommendations from others
Standard texts suggest that antacids1 or histamine (H2) blockers2 be used as first-line agents for reflux. Burrow and Duffyz3 recommend a stratified approach with antacids followed by H2-blockers, reserving the use of proton pump inhibitors for the more severe cases.
Evidence summary
Heartburn affects 30% to 50% of pregnancies and occurs primarily in the second and third trimesters.4 Lifestyle changes and dietary modification are recommended as initial measures for relief of symptoms.
Antacids
Each of the 3 identified placebo-controlled trials of antacid therapy had significant methodologic limitations. Aluminum phosphate more frequently produced complete relief of moderate to severe heartburn at 60 minutes compared with placebo (P <.001; number needed to treat [NNT] = 2.1 for mild heartburn and 20 for severe).5 Patients who received a combination of magnesium and aluminum hydroxide for 7 days had no more relief of symptoms than the placebo group.6 Atlay and colleagues7 found that sodium bicarbonate significantly reduced reflux symptoms compared with placebo (P=.021; NNT=6.0).
There are limited data regarding the safety of antacids during pregnancy. A single case-control study found a higher rate of congenital anomalies in children of women who took antacids in the first trimester (unadjusted odds ratio calculated from data=2.36; P <.05).8 This association was not detected when studied over the entire pregnancy. The rate of malformations was not different for magnesium, aluminum, and bicarbonate. The association could well be due to recall bias or other systematic biases inherent in case-control methodology.
H2-Blockers
The only identified studies of H2-blockers evaluated ranitidine. A 4-week double-blind randomized control trial found that ranitidine 150 mg twice daily reduced patient symptoms by 44% over placebo (P <.05).9 This study was limited by its short duration (<1 month) and small sample size (N=30). A 2-week study that compared antacids plus ranitidine to antacids alone found a 52% decrease in symptoms in the ranitidine group and a 44% reduction in the antacid-alone group.10 Ranitidine, cimetidine, and famotidine are US Food and Drug Administration (FDA) pregnancy category B (no demonstrated risk).
Proton Pump Inhibitors
In nonpregnant adults, proton pump inhibitors are more effective than antacids and H2-blockers for gastroesophageal reflux disease (GERD). No cohort or control studies have been performed on their efficacy in pregnancy. On the basis of animal studies, omeprazole is a category C drug (potential benefit of use should outweigh potential risks). A cohort study of 113 women found no associated anomalies (relative risk=1.94; 95% confidence interval, 0.36-10.36).11 Pantoprazole, lansoprazole and rabeprazole are category B medications.
Other Agents
Metoclopramide and sucralfate have been used in nonpregnant adults with GERD. Although both are category B, there are no data about their effectiveness for heartburn during pregnancy.
Donald N. Marquardt, PhD, MD
Iowa Health Physicians Cedar Rapids
Heartburn along with morning sickness and back pain frequently diminishes the joy of pregnancy. Simple nonpharmacologic solutions such as frequent small meals, remaining upright after eating, and elevating the head of the bed will often suffice. The traditional use of agents in their order of development (antacids, H2-blockers, then proton pump inhibitors) finds some justification in this review for selected agents. Particularly enlightening was the rationale for specific agents: aluminum phosphate has efficacy as an antacid; ranitidine is the only studied H2-blocker; and there are 3 FDA category B proton pump inhibitors (pantoprazole, lansoprazole, and rabeprazole). Specific recommendations for these agents would improve patient benefit with a minimum of therapeutic trials frustrating both patient and physician.
1. Gabbe SG, Niebyl JR, Simpson JL, Annas GJ, eds. Obstetrics: normal and problem pregnancies. 3rd ed. New York, NY: Churchill Livingstone; 1996.
2. Cunningham FG, Whitridge WJ. Williams obstetrics. 19th ed. Norwalk, Conn: Appleton & Lange; 1993.
3. Burrow GN, Duffy TP, eds. Medical complications during pregnancy. 5th ed. Philadelphia, Pa: WB Saunders; 1999.
4. Baron TH, Ramirez B, Richter JE. Gastrointestinal motility disorders during pregnancy. Ann Intern Med 1993;118:366-75.
5. Shaw RW. Randomized controlled trial of Syn-Ergel and an active placebo in the treatment of heartburn of pregnancy. J Int Med Res 1978;6:147-51.
6. Kovacs GT, Campbell J, Francis D, Hill D, Adena MA. Is mucaine an appropriate medication for the relief of heartburn during pregnancy?. Asia-Oceania J Obstet Gynaecol 1990;16:357-62.
7. Atlay RD, Weekes AR, Entwistle GD, Parkinson DJ. Treating heartburn in pregnancy: comparison of acid and alkali mixtures. BMJ 1978;2:919-20.
8. Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. BMJ 1971;1:523-27.
9. Larson JD, Patatanian E, Miner PB, Jr, Rayburn WF, Robinson MG. Double-blind, placebo-controlled study of ranitidine for gastroesophageal reflux symptoms during pregnancy. Obstet Gynecol 1997;90:83-87.
10. Rayburn W, Liles E, Christensen H, Robinson M. Antacids vs. antacids plus non-prescription ranitidine for heartburn during pregnancy. Int J Gynaecol Obstet 1999;66:35-37.
11. Lalkin A, Loebstein R, Addis A, et al. The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol 1998;179:727-30.
1. Gabbe SG, Niebyl JR, Simpson JL, Annas GJ, eds. Obstetrics: normal and problem pregnancies. 3rd ed. New York, NY: Churchill Livingstone; 1996.
2. Cunningham FG, Whitridge WJ. Williams obstetrics. 19th ed. Norwalk, Conn: Appleton & Lange; 1993.
3. Burrow GN, Duffy TP, eds. Medical complications during pregnancy. 5th ed. Philadelphia, Pa: WB Saunders; 1999.
4. Baron TH, Ramirez B, Richter JE. Gastrointestinal motility disorders during pregnancy. Ann Intern Med 1993;118:366-75.
5. Shaw RW. Randomized controlled trial of Syn-Ergel and an active placebo in the treatment of heartburn of pregnancy. J Int Med Res 1978;6:147-51.
6. Kovacs GT, Campbell J, Francis D, Hill D, Adena MA. Is mucaine an appropriate medication for the relief of heartburn during pregnancy?. Asia-Oceania J Obstet Gynaecol 1990;16:357-62.
7. Atlay RD, Weekes AR, Entwistle GD, Parkinson DJ. Treating heartburn in pregnancy: comparison of acid and alkali mixtures. BMJ 1978;2:919-20.
8. Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. BMJ 1971;1:523-27.
9. Larson JD, Patatanian E, Miner PB, Jr, Rayburn WF, Robinson MG. Double-blind, placebo-controlled study of ranitidine for gastroesophageal reflux symptoms during pregnancy. Obstet Gynecol 1997;90:83-87.
10. Rayburn W, Liles E, Christensen H, Robinson M. Antacids vs. antacids plus non-prescription ranitidine for heartburn during pregnancy. Int J Gynaecol Obstet 1999;66:35-37.
11. Lalkin A, Loebstein R, Addis A, et al. The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol 1998;179:727-30.
Evidence-based answers from the Family Physicians Inquiries Network
Antihistamines for Atopic Dermatitis
CLINICAL QUESTION: Do antihistamines relieve itching in atopic dermatitis?
BACKGROUND: Atopic dermatitis is a common malady characterized by intense pruritus. The itch-scratch cycle exacerbates the problem and is frequently treated with antihistamines, although there is little evidence for their effectiveness. population studied n Three European trials enrolled patients ranging in age from 11 to 67 years who met inclusion criteria for atopic dermatitis.
STUDY DESIGN AND VALIDITY: This was a systematic review in which the authors evaluated randomized controlled trials examining the effect of antihistamines on pruritis in atopic dermatitis. Sixteen studies were initially identified by searching MEDLINE (1966 to 1999), The Cochrane Database of Systematic Reviews, and Best Evidence databases. The authors used a modified version of Sackett’s criteria for clinical evidence to assess quality. Thirteen trials that received a grade of C by the Sackett criteria were excluded because of lack of randomization, placebo control, blinding, or a sample size of less than 20 people. The remaining 3 studies were randomized double-blind placebo-controlled trials. However, all had small sample sizes, and therefore received a grade of B. There were no grade-A studies.
Terfenadine, clemastine fumurate, and cetirizine hydrochloride were evaluated in these 3 studies. All 3 trials permitted the use of emollients and topical steroids. The first 2 studies enrolled fewer than 30 subjects but used a crossover design; this design reduces the needed sample size, since each patient reduces variance by serving as his or her own control. The cetirizine trial enrolled 178 patients who were divided into 4 parallel comparison groups.
The 3 studies suffered from small sample size, which can lead to the possibility of missing a benefit from antihistamines when one existed. Two of the studies excluded dropouts in their analysis, a potential threat to validity. The authors of the systematic review apparently did not contact authors of previous studies to see if additional data were available. Since all 3 of the studies used similar visual analog scales for rating pruritus and had similar patient groups, the data could have been pooled to allow a meta-analysis. Such a meta-analysis would not have been specific for any one of the studied antihistamines but would have helped overcome concerns about sample size.
OUTCOMES MEASURED: All 3 trials used visual analog scores to report the severity of pruritus. Investigator assessments (severity of excoriation or visual analog scores) were used in 2 of the studies. A computerized method of recording symptoms by patients was used in the third.
RESULTS: No improvement in pruritus was found in the 2 smaller crossover trials for terfenadine or clemastine fumurate. In the third trial, the 13 patients taking higher doses (40 mg) of cetirizine and experiencing sedation had an improved mean pruritus score. However, the range of scores overlapped considerably with patients who did not experience sedation, suggesting that the difference may not be significant. Unfortunately, no statistical analysis was done on the effect size.
Although the existing studies are limited in quality and quantity, this systematic review finds no evidence that second generation antihistamines are helpful in relieving pruritus due to atopic dermatitis. Clinical trials of better quality, employing a larger sample size and evaluating both first and second generation antihistamines, would be particularly helpful.
CLINICAL QUESTION: Do antihistamines relieve itching in atopic dermatitis?
BACKGROUND: Atopic dermatitis is a common malady characterized by intense pruritus. The itch-scratch cycle exacerbates the problem and is frequently treated with antihistamines, although there is little evidence for their effectiveness. population studied n Three European trials enrolled patients ranging in age from 11 to 67 years who met inclusion criteria for atopic dermatitis.
STUDY DESIGN AND VALIDITY: This was a systematic review in which the authors evaluated randomized controlled trials examining the effect of antihistamines on pruritis in atopic dermatitis. Sixteen studies were initially identified by searching MEDLINE (1966 to 1999), The Cochrane Database of Systematic Reviews, and Best Evidence databases. The authors used a modified version of Sackett’s criteria for clinical evidence to assess quality. Thirteen trials that received a grade of C by the Sackett criteria were excluded because of lack of randomization, placebo control, blinding, or a sample size of less than 20 people. The remaining 3 studies were randomized double-blind placebo-controlled trials. However, all had small sample sizes, and therefore received a grade of B. There were no grade-A studies.
Terfenadine, clemastine fumurate, and cetirizine hydrochloride were evaluated in these 3 studies. All 3 trials permitted the use of emollients and topical steroids. The first 2 studies enrolled fewer than 30 subjects but used a crossover design; this design reduces the needed sample size, since each patient reduces variance by serving as his or her own control. The cetirizine trial enrolled 178 patients who were divided into 4 parallel comparison groups.
The 3 studies suffered from small sample size, which can lead to the possibility of missing a benefit from antihistamines when one existed. Two of the studies excluded dropouts in their analysis, a potential threat to validity. The authors of the systematic review apparently did not contact authors of previous studies to see if additional data were available. Since all 3 of the studies used similar visual analog scales for rating pruritus and had similar patient groups, the data could have been pooled to allow a meta-analysis. Such a meta-analysis would not have been specific for any one of the studied antihistamines but would have helped overcome concerns about sample size.
OUTCOMES MEASURED: All 3 trials used visual analog scores to report the severity of pruritus. Investigator assessments (severity of excoriation or visual analog scores) were used in 2 of the studies. A computerized method of recording symptoms by patients was used in the third.
RESULTS: No improvement in pruritus was found in the 2 smaller crossover trials for terfenadine or clemastine fumurate. In the third trial, the 13 patients taking higher doses (40 mg) of cetirizine and experiencing sedation had an improved mean pruritus score. However, the range of scores overlapped considerably with patients who did not experience sedation, suggesting that the difference may not be significant. Unfortunately, no statistical analysis was done on the effect size.
Although the existing studies are limited in quality and quantity, this systematic review finds no evidence that second generation antihistamines are helpful in relieving pruritus due to atopic dermatitis. Clinical trials of better quality, employing a larger sample size and evaluating both first and second generation antihistamines, would be particularly helpful.
CLINICAL QUESTION: Do antihistamines relieve itching in atopic dermatitis?
BACKGROUND: Atopic dermatitis is a common malady characterized by intense pruritus. The itch-scratch cycle exacerbates the problem and is frequently treated with antihistamines, although there is little evidence for their effectiveness. population studied n Three European trials enrolled patients ranging in age from 11 to 67 years who met inclusion criteria for atopic dermatitis.
STUDY DESIGN AND VALIDITY: This was a systematic review in which the authors evaluated randomized controlled trials examining the effect of antihistamines on pruritis in atopic dermatitis. Sixteen studies were initially identified by searching MEDLINE (1966 to 1999), The Cochrane Database of Systematic Reviews, and Best Evidence databases. The authors used a modified version of Sackett’s criteria for clinical evidence to assess quality. Thirteen trials that received a grade of C by the Sackett criteria were excluded because of lack of randomization, placebo control, blinding, or a sample size of less than 20 people. The remaining 3 studies were randomized double-blind placebo-controlled trials. However, all had small sample sizes, and therefore received a grade of B. There were no grade-A studies.
Terfenadine, clemastine fumurate, and cetirizine hydrochloride were evaluated in these 3 studies. All 3 trials permitted the use of emollients and topical steroids. The first 2 studies enrolled fewer than 30 subjects but used a crossover design; this design reduces the needed sample size, since each patient reduces variance by serving as his or her own control. The cetirizine trial enrolled 178 patients who were divided into 4 parallel comparison groups.
The 3 studies suffered from small sample size, which can lead to the possibility of missing a benefit from antihistamines when one existed. Two of the studies excluded dropouts in their analysis, a potential threat to validity. The authors of the systematic review apparently did not contact authors of previous studies to see if additional data were available. Since all 3 of the studies used similar visual analog scales for rating pruritus and had similar patient groups, the data could have been pooled to allow a meta-analysis. Such a meta-analysis would not have been specific for any one of the studied antihistamines but would have helped overcome concerns about sample size.
OUTCOMES MEASURED: All 3 trials used visual analog scores to report the severity of pruritus. Investigator assessments (severity of excoriation or visual analog scores) were used in 2 of the studies. A computerized method of recording symptoms by patients was used in the third.
RESULTS: No improvement in pruritus was found in the 2 smaller crossover trials for terfenadine or clemastine fumurate. In the third trial, the 13 patients taking higher doses (40 mg) of cetirizine and experiencing sedation had an improved mean pruritus score. However, the range of scores overlapped considerably with patients who did not experience sedation, suggesting that the difference may not be significant. Unfortunately, no statistical analysis was done on the effect size.
Although the existing studies are limited in quality and quantity, this systematic review finds no evidence that second generation antihistamines are helpful in relieving pruritus due to atopic dermatitis. Clinical trials of better quality, employing a larger sample size and evaluating both first and second generation antihistamines, would be particularly helpful.