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Should we discontinue Pap smear screening in women aged >65 years?
Women with a history of regular, normal Pap smear screening should discontinue screening by age 65 years (strength of recommendation [SOR]: B). Women without a history of serial normal Pap smears should continue screening (SOR: B).
Evidence summary
There is little direct evidence to support discontinuation of Pap screening in older women, but indirect evidence demonstrates that screening has reduced value in women with a history of periodic, normal Pap screening.
A systematic review of 12 studies from 1995 to 2001, which included women aged 50 years and older stratified by age and outcomes, showed that the risk of high-grade cervical lesions falls with age, and that a history of normal Pap tests further reduces that risk.1 This observational evidence is based on large population-based cohort studies and a few prospective cohort studies.
According to this review, fewer than 1 in 1000 (and possibly as few as 2 in 10,000) women aged >60 years with a history of a normal baseline Pap smear will develop cervical intraepithelial neoplasia (CIN) 3 or cancer. By comparison, women being screened for the first time had rates of CIN 3 or cancer at 2.3 per 1000 for ages 50 to 64 years, and 1.7 per 1000 for women aged 65 years.
A prospective study of older women (average age, 66.7 years) followed for 2 years after a normal Pap smear result found an incidence of Pap smear abnormalities of 110 per 4895 (23 per 1000 person-years; 95% confidence interval [CI], 18–27 per 1000), but only 1 result of the 110 was a true positive (0.2 per 1000 person-years).2
A retrospective review of 798 cases of CIN or worse diagnosed in Scotland from 1989 to 1990 found that 98% of CIN occurred in women aged ≥50 years.3 Given a low prevalence of true positive high-grade Pap smears in elderly women with a history of normal Pap smear results, elderly women are disproportionately likely to have evaluations for false-positive results.1 With an estimated sensitivity of 60% and specificity of 98%, continued Pap screening would result in at least 34 elderly women being evaluated for high-grade Pap smears for every 1 true positive; and for every 3 cases identified, 2 would be missed.1 As a comparison, for women of all ages with a high-grade Pap smear, 70% to 75% will have CIN 2 or 3, and 1% to 2% will have invasive carcinoma.4
Several studies support the conclusion that women aged >65 years without a history of regular normal Pap smear results continue to benefit from cervical cancer screening. A prospective study of an urban, low-income population in New York (average age, 74) who were previously inadequately screened (≥5 years since last Pap smear in 75%) or had no previous screening (25%) found an incidence of 15.9 per 1000 of abnormal Pap smear results (95% CI, 8.5–23.3).5
The results of Pap screening among older women were analyzed in the retrospective review from the population-based registry of the Ontario Cervical Screening Program for almost 700,000 women screened during the first 6 months in 2000.6 In this population, over 80% of women aged 50 years with high-grade lesion or carcinoma had a history of either no Pap screening or a previously abnormal test result in the past 4 years. Nonparticipants in Pap screening had a 2.7 to 4 times greater risk of cervical cancer than women screened at least once before.4
In the US, after Medicare began coverage for Pap smear screening in women age 65 and older, increased screening has resulted in more diagnoses of carcinoma in situ and a reduction in cervical cancer.7
A cost-benefit analysis, designed and published in 1992, evaluated Pap smear screening in the elderly with a Markov mathematical model. This model predicted the outcomes of periodic screening, diagnosis, and treatment for cervical cancer in hypothetical cohorts of women aged 65 to 109 years.8 The Table depicts the cost per year of life saved for each Pap smear screening cohort of women analyzed in the Markov mathematical model. These data demonstrate cost-effectiveness of continued screening in elderly women who have not received adequate screening previously, while showing high cost-to-benefit ratio for continued screening in women with previous normal Pap smear results.
In a hypothetical cohort of elderly women who were never screened, annual Pap smear screening would cost less than $6500 per year of life saved. The cost per year of life saved in women who have received regular screening every 3 years would be $33,572.
TABLE
Cost-benefit analysis of Pap smear screening
| Patient | Screening frequency | Cost per year of life saved |
|---|---|---|
| All women aged≥65 years | Every 3 years | $7000 |
| Women aged≥65 years without a previous Pap or Pap within 5 years | Every year | <$6500 |
| Women aged≥65 years with a history of normal, regular Pap smear results | Every 3 years | $33,572 |
Recommendations from others
The 2002 guidelines from the American Cancer Society recommend that women aged 70 and older who have had 3 consecutive normal Pap smear results and no abnormal results in the past 10 years may choose to stop cervical cancer screening.9 The 2003 guidelines from the US Preventive Services Task Force recommend discontinuing Pap smear screening after age 65 if previous Pap results were consistently normal.10 In 1994, the Canadian Task Force on Preventive Health Care recommended stopping screening at age 70 if women have had at least 4 negative Pap smear results in the preceding 10 years and if previous results were normal.11 The American College of Obstetrics and Gynecology recommends physicians determine when to stop screening on an individual basis, and notes that limited studies of older women made it difficult to set an upper age limit for Pap smears.12
Medicare covers Pap smears every 3 years, but will pay for yearly screening for women who have had an abnormal Pap result in the preceding 3 years and for women at high risk of cervical or vaginal cancer.
Stop Pap smears at 65 for those with normal prior screening, low risk for HPV
Jon O. Neher, MD
Valley Medical Center Family Practice Residency, Renton, Wash
My older patients are delighted to stop having Pap smears and want to quit as soon as possible. The test can become quite an ordeal with advancing age as cervical stenosis, vaginal atrophy, and hip arthritis increase patient discomfort and technical difficulty. Following the lead of the US Preventive Services Task Force, I stop recommending them at age 65 for most patients who have a record of recent normal Pap smear results.
However, older adults are sexual beings, and HPV transmission can occur among those who are sexually active outside a long-term mutually monogamous relationship. When counseling women with high-risk lifestyles, I will discuss the possibility of continuing regular Pap smears beyond 65 years of age.
1. Hartmann KE, Hall SA, Nanda K, Boggess JF, Zolnoun D. Screening for Cervical Cancer. Systematic Evidence Review number 25. Rockville, Md: Agency for Healthcare Research and Quality; 2002. Available at: www.ahrq.gov/clinic/prev/crvcainv.htm. Accessed on March 9, 2004.
2. Sawaya GF, Grady D, Kerlikowske K, et al. The positive predictive value of cervical smears in previously screened postmenopausal women: the Heart and Estrogen/progestin Replacement Study (HERS). Ann Intern Med 2000;133:942-950.
3. Van Wijngaarden WJ, Duncan ID. Rationale for stopping cervical screening in women over 50. BMJ 1993;306:967-971.
4. Wright TC, Jr, Cox JT, Massad LS, Twiggs LS, Wilkinson EJ. ASCCP-Sponsored Consensus Conference. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287:2120-2129.
5. Mandelblatt J, Gopaul I, Wistreich M. Gynecological care of elderly women. Another look at Papanicolaou smear testing. JAMA 1986;256:367-371.
6. Colgan TJ, Clarke A, Hakh N, Seidenfeld A. Screening for cervical disease in mature women: strategies for improvement. Cancer 2002;96:195-203.
7. Cornelison TL, Montz FJ, Bristow RE, Chou B, Bovicelli A, Zeger SL. Decreased incidence of cervical cancer in medicare-eligible California women. Obstet Gynecol 2002;100:79-86.
8. Fahs MC, Mandelblatt J, Schechter C, Muller C. Cost effectiveness of cervical cancer screening for the elderly. Ann Intern Med 1992;117:520-527.
9. Saslow D, Runowicz CD, Solomon D, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002;52:342-362.
10. US Preventive Task Force. Cervical Cancer Screening. January 2003. Rockville, Md: Agency for Healthcare Research and Quality. Available at: www.ahrq.gov/clinic/uspstf/uspscerv.htm. Accessed on March 9, 2004.
11. Morrison BJ. Screening for cervical cancer. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: HealthCanada; 1994;870-881.Availableat: www.hcsc.gc.ca/hppb/healthcare/pubs/clinical_prventive/sec10e.htm. Accessed on March 18, 2004.
12. American College of Gyncology Committee on Practice Bulletins. ACOG Practice Bulletin: clinical management guidelines for obstetricians-gynecologists. Number 45, August 2003. Cervical cytology screening. Obstet Gynecol 2003;102:417-427.
Women with a history of regular, normal Pap smear screening should discontinue screening by age 65 years (strength of recommendation [SOR]: B). Women without a history of serial normal Pap smears should continue screening (SOR: B).
Evidence summary
There is little direct evidence to support discontinuation of Pap screening in older women, but indirect evidence demonstrates that screening has reduced value in women with a history of periodic, normal Pap screening.
A systematic review of 12 studies from 1995 to 2001, which included women aged 50 years and older stratified by age and outcomes, showed that the risk of high-grade cervical lesions falls with age, and that a history of normal Pap tests further reduces that risk.1 This observational evidence is based on large population-based cohort studies and a few prospective cohort studies.
According to this review, fewer than 1 in 1000 (and possibly as few as 2 in 10,000) women aged >60 years with a history of a normal baseline Pap smear will develop cervical intraepithelial neoplasia (CIN) 3 or cancer. By comparison, women being screened for the first time had rates of CIN 3 or cancer at 2.3 per 1000 for ages 50 to 64 years, and 1.7 per 1000 for women aged 65 years.
A prospective study of older women (average age, 66.7 years) followed for 2 years after a normal Pap smear result found an incidence of Pap smear abnormalities of 110 per 4895 (23 per 1000 person-years; 95% confidence interval [CI], 18–27 per 1000), but only 1 result of the 110 was a true positive (0.2 per 1000 person-years).2
A retrospective review of 798 cases of CIN or worse diagnosed in Scotland from 1989 to 1990 found that 98% of CIN occurred in women aged ≥50 years.3 Given a low prevalence of true positive high-grade Pap smears in elderly women with a history of normal Pap smear results, elderly women are disproportionately likely to have evaluations for false-positive results.1 With an estimated sensitivity of 60% and specificity of 98%, continued Pap screening would result in at least 34 elderly women being evaluated for high-grade Pap smears for every 1 true positive; and for every 3 cases identified, 2 would be missed.1 As a comparison, for women of all ages with a high-grade Pap smear, 70% to 75% will have CIN 2 or 3, and 1% to 2% will have invasive carcinoma.4
Several studies support the conclusion that women aged >65 years without a history of regular normal Pap smear results continue to benefit from cervical cancer screening. A prospective study of an urban, low-income population in New York (average age, 74) who were previously inadequately screened (≥5 years since last Pap smear in 75%) or had no previous screening (25%) found an incidence of 15.9 per 1000 of abnormal Pap smear results (95% CI, 8.5–23.3).5
The results of Pap screening among older women were analyzed in the retrospective review from the population-based registry of the Ontario Cervical Screening Program for almost 700,000 women screened during the first 6 months in 2000.6 In this population, over 80% of women aged 50 years with high-grade lesion or carcinoma had a history of either no Pap screening or a previously abnormal test result in the past 4 years. Nonparticipants in Pap screening had a 2.7 to 4 times greater risk of cervical cancer than women screened at least once before.4
In the US, after Medicare began coverage for Pap smear screening in women age 65 and older, increased screening has resulted in more diagnoses of carcinoma in situ and a reduction in cervical cancer.7
A cost-benefit analysis, designed and published in 1992, evaluated Pap smear screening in the elderly with a Markov mathematical model. This model predicted the outcomes of periodic screening, diagnosis, and treatment for cervical cancer in hypothetical cohorts of women aged 65 to 109 years.8 The Table depicts the cost per year of life saved for each Pap smear screening cohort of women analyzed in the Markov mathematical model. These data demonstrate cost-effectiveness of continued screening in elderly women who have not received adequate screening previously, while showing high cost-to-benefit ratio for continued screening in women with previous normal Pap smear results.
In a hypothetical cohort of elderly women who were never screened, annual Pap smear screening would cost less than $6500 per year of life saved. The cost per year of life saved in women who have received regular screening every 3 years would be $33,572.
TABLE
Cost-benefit analysis of Pap smear screening
| Patient | Screening frequency | Cost per year of life saved |
|---|---|---|
| All women aged≥65 years | Every 3 years | $7000 |
| Women aged≥65 years without a previous Pap or Pap within 5 years | Every year | <$6500 |
| Women aged≥65 years with a history of normal, regular Pap smear results | Every 3 years | $33,572 |
Recommendations from others
The 2002 guidelines from the American Cancer Society recommend that women aged 70 and older who have had 3 consecutive normal Pap smear results and no abnormal results in the past 10 years may choose to stop cervical cancer screening.9 The 2003 guidelines from the US Preventive Services Task Force recommend discontinuing Pap smear screening after age 65 if previous Pap results were consistently normal.10 In 1994, the Canadian Task Force on Preventive Health Care recommended stopping screening at age 70 if women have had at least 4 negative Pap smear results in the preceding 10 years and if previous results were normal.11 The American College of Obstetrics and Gynecology recommends physicians determine when to stop screening on an individual basis, and notes that limited studies of older women made it difficult to set an upper age limit for Pap smears.12
Medicare covers Pap smears every 3 years, but will pay for yearly screening for women who have had an abnormal Pap result in the preceding 3 years and for women at high risk of cervical or vaginal cancer.
Stop Pap smears at 65 for those with normal prior screening, low risk for HPV
Jon O. Neher, MD
Valley Medical Center Family Practice Residency, Renton, Wash
My older patients are delighted to stop having Pap smears and want to quit as soon as possible. The test can become quite an ordeal with advancing age as cervical stenosis, vaginal atrophy, and hip arthritis increase patient discomfort and technical difficulty. Following the lead of the US Preventive Services Task Force, I stop recommending them at age 65 for most patients who have a record of recent normal Pap smear results.
However, older adults are sexual beings, and HPV transmission can occur among those who are sexually active outside a long-term mutually monogamous relationship. When counseling women with high-risk lifestyles, I will discuss the possibility of continuing regular Pap smears beyond 65 years of age.
Women with a history of regular, normal Pap smear screening should discontinue screening by age 65 years (strength of recommendation [SOR]: B). Women without a history of serial normal Pap smears should continue screening (SOR: B).
Evidence summary
There is little direct evidence to support discontinuation of Pap screening in older women, but indirect evidence demonstrates that screening has reduced value in women with a history of periodic, normal Pap screening.
A systematic review of 12 studies from 1995 to 2001, which included women aged 50 years and older stratified by age and outcomes, showed that the risk of high-grade cervical lesions falls with age, and that a history of normal Pap tests further reduces that risk.1 This observational evidence is based on large population-based cohort studies and a few prospective cohort studies.
According to this review, fewer than 1 in 1000 (and possibly as few as 2 in 10,000) women aged >60 years with a history of a normal baseline Pap smear will develop cervical intraepithelial neoplasia (CIN) 3 or cancer. By comparison, women being screened for the first time had rates of CIN 3 or cancer at 2.3 per 1000 for ages 50 to 64 years, and 1.7 per 1000 for women aged 65 years.
A prospective study of older women (average age, 66.7 years) followed for 2 years after a normal Pap smear result found an incidence of Pap smear abnormalities of 110 per 4895 (23 per 1000 person-years; 95% confidence interval [CI], 18–27 per 1000), but only 1 result of the 110 was a true positive (0.2 per 1000 person-years).2
A retrospective review of 798 cases of CIN or worse diagnosed in Scotland from 1989 to 1990 found that 98% of CIN occurred in women aged ≥50 years.3 Given a low prevalence of true positive high-grade Pap smears in elderly women with a history of normal Pap smear results, elderly women are disproportionately likely to have evaluations for false-positive results.1 With an estimated sensitivity of 60% and specificity of 98%, continued Pap screening would result in at least 34 elderly women being evaluated for high-grade Pap smears for every 1 true positive; and for every 3 cases identified, 2 would be missed.1 As a comparison, for women of all ages with a high-grade Pap smear, 70% to 75% will have CIN 2 or 3, and 1% to 2% will have invasive carcinoma.4
Several studies support the conclusion that women aged >65 years without a history of regular normal Pap smear results continue to benefit from cervical cancer screening. A prospective study of an urban, low-income population in New York (average age, 74) who were previously inadequately screened (≥5 years since last Pap smear in 75%) or had no previous screening (25%) found an incidence of 15.9 per 1000 of abnormal Pap smear results (95% CI, 8.5–23.3).5
The results of Pap screening among older women were analyzed in the retrospective review from the population-based registry of the Ontario Cervical Screening Program for almost 700,000 women screened during the first 6 months in 2000.6 In this population, over 80% of women aged 50 years with high-grade lesion or carcinoma had a history of either no Pap screening or a previously abnormal test result in the past 4 years. Nonparticipants in Pap screening had a 2.7 to 4 times greater risk of cervical cancer than women screened at least once before.4
In the US, after Medicare began coverage for Pap smear screening in women age 65 and older, increased screening has resulted in more diagnoses of carcinoma in situ and a reduction in cervical cancer.7
A cost-benefit analysis, designed and published in 1992, evaluated Pap smear screening in the elderly with a Markov mathematical model. This model predicted the outcomes of periodic screening, diagnosis, and treatment for cervical cancer in hypothetical cohorts of women aged 65 to 109 years.8 The Table depicts the cost per year of life saved for each Pap smear screening cohort of women analyzed in the Markov mathematical model. These data demonstrate cost-effectiveness of continued screening in elderly women who have not received adequate screening previously, while showing high cost-to-benefit ratio for continued screening in women with previous normal Pap smear results.
In a hypothetical cohort of elderly women who were never screened, annual Pap smear screening would cost less than $6500 per year of life saved. The cost per year of life saved in women who have received regular screening every 3 years would be $33,572.
TABLE
Cost-benefit analysis of Pap smear screening
| Patient | Screening frequency | Cost per year of life saved |
|---|---|---|
| All women aged≥65 years | Every 3 years | $7000 |
| Women aged≥65 years without a previous Pap or Pap within 5 years | Every year | <$6500 |
| Women aged≥65 years with a history of normal, regular Pap smear results | Every 3 years | $33,572 |
Recommendations from others
The 2002 guidelines from the American Cancer Society recommend that women aged 70 and older who have had 3 consecutive normal Pap smear results and no abnormal results in the past 10 years may choose to stop cervical cancer screening.9 The 2003 guidelines from the US Preventive Services Task Force recommend discontinuing Pap smear screening after age 65 if previous Pap results were consistently normal.10 In 1994, the Canadian Task Force on Preventive Health Care recommended stopping screening at age 70 if women have had at least 4 negative Pap smear results in the preceding 10 years and if previous results were normal.11 The American College of Obstetrics and Gynecology recommends physicians determine when to stop screening on an individual basis, and notes that limited studies of older women made it difficult to set an upper age limit for Pap smears.12
Medicare covers Pap smears every 3 years, but will pay for yearly screening for women who have had an abnormal Pap result in the preceding 3 years and for women at high risk of cervical or vaginal cancer.
Stop Pap smears at 65 for those with normal prior screening, low risk for HPV
Jon O. Neher, MD
Valley Medical Center Family Practice Residency, Renton, Wash
My older patients are delighted to stop having Pap smears and want to quit as soon as possible. The test can become quite an ordeal with advancing age as cervical stenosis, vaginal atrophy, and hip arthritis increase patient discomfort and technical difficulty. Following the lead of the US Preventive Services Task Force, I stop recommending them at age 65 for most patients who have a record of recent normal Pap smear results.
However, older adults are sexual beings, and HPV transmission can occur among those who are sexually active outside a long-term mutually monogamous relationship. When counseling women with high-risk lifestyles, I will discuss the possibility of continuing regular Pap smears beyond 65 years of age.
1. Hartmann KE, Hall SA, Nanda K, Boggess JF, Zolnoun D. Screening for Cervical Cancer. Systematic Evidence Review number 25. Rockville, Md: Agency for Healthcare Research and Quality; 2002. Available at: www.ahrq.gov/clinic/prev/crvcainv.htm. Accessed on March 9, 2004.
2. Sawaya GF, Grady D, Kerlikowske K, et al. The positive predictive value of cervical smears in previously screened postmenopausal women: the Heart and Estrogen/progestin Replacement Study (HERS). Ann Intern Med 2000;133:942-950.
3. Van Wijngaarden WJ, Duncan ID. Rationale for stopping cervical screening in women over 50. BMJ 1993;306:967-971.
4. Wright TC, Jr, Cox JT, Massad LS, Twiggs LS, Wilkinson EJ. ASCCP-Sponsored Consensus Conference. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287:2120-2129.
5. Mandelblatt J, Gopaul I, Wistreich M. Gynecological care of elderly women. Another look at Papanicolaou smear testing. JAMA 1986;256:367-371.
6. Colgan TJ, Clarke A, Hakh N, Seidenfeld A. Screening for cervical disease in mature women: strategies for improvement. Cancer 2002;96:195-203.
7. Cornelison TL, Montz FJ, Bristow RE, Chou B, Bovicelli A, Zeger SL. Decreased incidence of cervical cancer in medicare-eligible California women. Obstet Gynecol 2002;100:79-86.
8. Fahs MC, Mandelblatt J, Schechter C, Muller C. Cost effectiveness of cervical cancer screening for the elderly. Ann Intern Med 1992;117:520-527.
9. Saslow D, Runowicz CD, Solomon D, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002;52:342-362.
10. US Preventive Task Force. Cervical Cancer Screening. January 2003. Rockville, Md: Agency for Healthcare Research and Quality. Available at: www.ahrq.gov/clinic/uspstf/uspscerv.htm. Accessed on March 9, 2004.
11. Morrison BJ. Screening for cervical cancer. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: HealthCanada; 1994;870-881.Availableat: www.hcsc.gc.ca/hppb/healthcare/pubs/clinical_prventive/sec10e.htm. Accessed on March 18, 2004.
12. American College of Gyncology Committee on Practice Bulletins. ACOG Practice Bulletin: clinical management guidelines for obstetricians-gynecologists. Number 45, August 2003. Cervical cytology screening. Obstet Gynecol 2003;102:417-427.
1. Hartmann KE, Hall SA, Nanda K, Boggess JF, Zolnoun D. Screening for Cervical Cancer. Systematic Evidence Review number 25. Rockville, Md: Agency for Healthcare Research and Quality; 2002. Available at: www.ahrq.gov/clinic/prev/crvcainv.htm. Accessed on March 9, 2004.
2. Sawaya GF, Grady D, Kerlikowske K, et al. The positive predictive value of cervical smears in previously screened postmenopausal women: the Heart and Estrogen/progestin Replacement Study (HERS). Ann Intern Med 2000;133:942-950.
3. Van Wijngaarden WJ, Duncan ID. Rationale for stopping cervical screening in women over 50. BMJ 1993;306:967-971.
4. Wright TC, Jr, Cox JT, Massad LS, Twiggs LS, Wilkinson EJ. ASCCP-Sponsored Consensus Conference. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287:2120-2129.
5. Mandelblatt J, Gopaul I, Wistreich M. Gynecological care of elderly women. Another look at Papanicolaou smear testing. JAMA 1986;256:367-371.
6. Colgan TJ, Clarke A, Hakh N, Seidenfeld A. Screening for cervical disease in mature women: strategies for improvement. Cancer 2002;96:195-203.
7. Cornelison TL, Montz FJ, Bristow RE, Chou B, Bovicelli A, Zeger SL. Decreased incidence of cervical cancer in medicare-eligible California women. Obstet Gynecol 2002;100:79-86.
8. Fahs MC, Mandelblatt J, Schechter C, Muller C. Cost effectiveness of cervical cancer screening for the elderly. Ann Intern Med 1992;117:520-527.
9. Saslow D, Runowicz CD, Solomon D, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002;52:342-362.
10. US Preventive Task Force. Cervical Cancer Screening. January 2003. Rockville, Md: Agency for Healthcare Research and Quality. Available at: www.ahrq.gov/clinic/uspstf/uspscerv.htm. Accessed on March 9, 2004.
11. Morrison BJ. Screening for cervical cancer. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: HealthCanada; 1994;870-881.Availableat: www.hcsc.gc.ca/hppb/healthcare/pubs/clinical_prventive/sec10e.htm. Accessed on March 18, 2004.
12. American College of Gyncology Committee on Practice Bulletins. ACOG Practice Bulletin: clinical management guidelines for obstetricians-gynecologists. Number 45, August 2003. Cervical cytology screening. Obstet Gynecol 2003;102:417-427.
Evidence-based answers from the Family Physicians Inquiries Network
What is the best hypnotic for use in the elderly?
Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines (strength of recommendation: B, based on extrapolations of randomized controlled trials). Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.
Evidence summary
Zolpidem and zaleplon
Zolpidem and zaleplon differ structurally from benzodiazepines but act at the benzodiazepine receptor.1 Due to their rapid absorption and short half-lives, they are particularly helpful for patients who have trouble falling asleep.2 They have been shown to decrease sleep latency, increase total sleep time, and increase sleep efficiency without disturbing sleep architecture or adversely affecting memory.1
Comparative studies in the elderly have demonstrated that zolpidem is as effective as triazolam,3 and that zaleplon is more effective than placebo at decreasing sleep latency and improving sleep quality.4 Tolerance, withdrawal symptoms, or rebound insomnia occur less frequently than with benzodi-azepines,1 but zolpidem increased risk of hip fracture in a case control study (adjusted odds ratio=1.95, 95% confidence interval, 1.09–3.51).5
Side effects of zolpidem and zaleplon are considered dose-related, and a lower dose of 5 mg is recommended for older patients.2 Efficacy of intermittent use of zolpidem has been demonstrated in clinical studies,1 a practice that could potentially decrease risk of side effects. Overall, if a hypnotic is desired for an older adult, zolpidem and zaleplon are preferred because of their improved side-effect profiles compared with older hypnotics such as benzodiazepines, chloral hydrate, over-the-counter sleep aids, and antidepressants (see Table ).
TABLE 1
Adverse effects of hypnotics in the elderly
| Hypnotic | Adverse effect |
|---|---|
| Benzodiazepines | Somnolence, anterograde amnesia, falls, hip fracture, rebound insomnia, tolerance, dependence, impaired sleep architecture2,3,5 |
| Antihistamines | Somnolence, dry mouth, constipation, urinary retention, blurred vision, cognitive changes3 |
| Valerian | Headache, excitability, uneasiness, cardiac disturbances, insomnia, drowsiness, withdrawal symptoms10 |
| Melatonin | Headache, depressive symptoms, daytime fatigue and drowsiness, dizziness, abdominal cramps, reduced alertness10 |
| Chloral hydrate | Nausea, vomiting, diarrhea, may increase effects of warfarin, overdose potential3,8 |
| Tricyclic antidepressants | Dry mouth, constipation, urinary retention, blurred vision, cognitive changes, orthostatic hypotension, somnolence, worsening of chronic heart failure, overdose potential, cardiac conduction abnormalities2,3 |
| Trazodone | Somnolence, orthostatic hypotension, dry mouth, priapism3 |
| Zolpidem | Drowsiness, headache, dizziness, somnolence, fatigue, agitation, nightmares, diarrhea, myalgia, arthralgia, anterograde amnesia1,10 |
| Zaleplon | Headache, dizziness, somnolence, short-term amnesic effects, next-day memory impairment, mild rebound insomnia1,10 |
Benzodiazepines
Benzodiazepines have been used since the 1960s for their hypnotic, anxiolytic, anticonvulsant, muscle-relaxing, and amnesic properties. A recent meta-analysis showed that benzodiazepines improve sleep latency by only 4.2 minutes compared with placebo.6 Although benzodiazepines increase sleep time and efficiency, patients quickly develop tolerance to the hypnotic effects.7 Additional problems associated with benzodiazepines include dependence, rebound insomnia, residual sedation, falls, hip fractures, and detrimental effects on sleep architecture.7
Chloral hydrate
Chloral hydrate has a narrow therapeutic index and is not recommended for the treatment of insomnia.8 Tolerance to its effects develops after only 2 weeks of use, and drug interactions with warfarin can occur.2
Over-the-counter sleep aids
Most over-the-counter sleep aids contain diphen-hydramine, a long-acting antihistamine that is considered less effective than benzodiazepines. The anticholinergic properties of antihistamines can result in cognitive changes and urinary retention in the elderly.8 Melatonin and valerian are “natural” hypnotics that are available without a prescription,9 but their safety and efficacy are not regulated by the FDA.8
Antidepressants
Antidepressants with sedative effects, such as tricyclic antidepressants and trazodone, have been used for insomnia, but minimal data support the efficacy or safety of this approach.8 Tricyclic antidepressants may exacerbate restless legs syndrome and periodic limb movement disorder,8 cause anticholinergic side effects, worsen chronic heart failure, and cause ortho-static hypotension and falls.2 Although tra-zodone is not a tricyclic antidepressant, it can cause dry mouth, orthostatic hypotension, and (rarely) priapism.2
Recommendations from others
A Canadian consensus statement published in 2003 supports the use of non-benzodiazepines such as zolpidem and zaleplon due to improved tolerability, and less withdrawal and abuse potential compared with benzodiazepines.7 The National Heart, Lung and Blood Institute Working Group on Insomnia recommends the use of short-acting hypnotics for short-term management of insomnia, but does not differentiate between short-acting benzodiazepines and the newer hypnotics such as zolpidem and zale-plon.8 Geriatric experts recommend that long-acting benzodiazepines, barbiturates, and amitriptyline be avoided in the elderly due to the risk of adverse drug events.10
Question the patient about sleep habits
David Cravens, MD, MSPH
Department of Family & Community Medicine, University of Missouri–Columbia
Sleep complaints are common in the elderly. However, before prescribing a hypnotic, determine the elderly patient’s sleep habits: often daytime naps plus nighttime sleep add up to adequate sleep. Encourage measures to avoid daytime naps if nighttime sleep is more important. Second, discuss sleep hygiene, such as avoiding evening caffeine or excessive alcohol, and avoiding using bed for activities other than sleeping, such as watching TV, reading, and the like. Determine whether sleep problems are part of a larger problem requiring evaluation, such as medication effects, depression, or obstructive sleep apnea. Finally, consider costs: although not a true hypnotic, trazodone at doses of 25–50 mg is a very effective and well-tolerated soporific at about one-tenth the cost of 5 mg of zolpidem or zaleplon.
1. Terzano MG, Rossi M, Palomba V, Smerien A, Parrino L. New drugs for insomnia: comparative tolerability of zopiclone, zolpi-dem and zaleplon. Drug Saf 2003;26:261-282.
2. McEvoy GK, Miller J, Litvak K, et al. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2003;2400-2405.
3. Roger M, Attali P, Coquelin JP. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993;15:127-136.
4. Hedner J, Yaeche R, Emilien G, Farr I, Salinas E. Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry 2000;15:704-712.
5. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avom J. Zolpidem use and hip fractures in older people. J Am Geriatr Soc 2001;49:1685-1690.
6. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162:225-233.
7. Montplaisir J, Hawa R, Moller H, et al. Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Hum Psychopharmacol 2003;18:29-38.
8. Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Institute Working Group on Insomnia. Am Fam Physician 1999;59:3029-3038.
9. Jellin JM, Gregory P, Batz F, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 3rd ed. Stockton, Calif: Therapeutic Research Faculty; 2000;723-7251052-1053.
10. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update. Arch Intern Med 1997;157:1531-1536.
Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines (strength of recommendation: B, based on extrapolations of randomized controlled trials). Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.
Evidence summary
Zolpidem and zaleplon
Zolpidem and zaleplon differ structurally from benzodiazepines but act at the benzodiazepine receptor.1 Due to their rapid absorption and short half-lives, they are particularly helpful for patients who have trouble falling asleep.2 They have been shown to decrease sleep latency, increase total sleep time, and increase sleep efficiency without disturbing sleep architecture or adversely affecting memory.1
Comparative studies in the elderly have demonstrated that zolpidem is as effective as triazolam,3 and that zaleplon is more effective than placebo at decreasing sleep latency and improving sleep quality.4 Tolerance, withdrawal symptoms, or rebound insomnia occur less frequently than with benzodi-azepines,1 but zolpidem increased risk of hip fracture in a case control study (adjusted odds ratio=1.95, 95% confidence interval, 1.09–3.51).5
Side effects of zolpidem and zaleplon are considered dose-related, and a lower dose of 5 mg is recommended for older patients.2 Efficacy of intermittent use of zolpidem has been demonstrated in clinical studies,1 a practice that could potentially decrease risk of side effects. Overall, if a hypnotic is desired for an older adult, zolpidem and zaleplon are preferred because of their improved side-effect profiles compared with older hypnotics such as benzodiazepines, chloral hydrate, over-the-counter sleep aids, and antidepressants (see Table ).
TABLE 1
Adverse effects of hypnotics in the elderly
| Hypnotic | Adverse effect |
|---|---|
| Benzodiazepines | Somnolence, anterograde amnesia, falls, hip fracture, rebound insomnia, tolerance, dependence, impaired sleep architecture2,3,5 |
| Antihistamines | Somnolence, dry mouth, constipation, urinary retention, blurred vision, cognitive changes3 |
| Valerian | Headache, excitability, uneasiness, cardiac disturbances, insomnia, drowsiness, withdrawal symptoms10 |
| Melatonin | Headache, depressive symptoms, daytime fatigue and drowsiness, dizziness, abdominal cramps, reduced alertness10 |
| Chloral hydrate | Nausea, vomiting, diarrhea, may increase effects of warfarin, overdose potential3,8 |
| Tricyclic antidepressants | Dry mouth, constipation, urinary retention, blurred vision, cognitive changes, orthostatic hypotension, somnolence, worsening of chronic heart failure, overdose potential, cardiac conduction abnormalities2,3 |
| Trazodone | Somnolence, orthostatic hypotension, dry mouth, priapism3 |
| Zolpidem | Drowsiness, headache, dizziness, somnolence, fatigue, agitation, nightmares, diarrhea, myalgia, arthralgia, anterograde amnesia1,10 |
| Zaleplon | Headache, dizziness, somnolence, short-term amnesic effects, next-day memory impairment, mild rebound insomnia1,10 |
Benzodiazepines
Benzodiazepines have been used since the 1960s for their hypnotic, anxiolytic, anticonvulsant, muscle-relaxing, and amnesic properties. A recent meta-analysis showed that benzodiazepines improve sleep latency by only 4.2 minutes compared with placebo.6 Although benzodiazepines increase sleep time and efficiency, patients quickly develop tolerance to the hypnotic effects.7 Additional problems associated with benzodiazepines include dependence, rebound insomnia, residual sedation, falls, hip fractures, and detrimental effects on sleep architecture.7
Chloral hydrate
Chloral hydrate has a narrow therapeutic index and is not recommended for the treatment of insomnia.8 Tolerance to its effects develops after only 2 weeks of use, and drug interactions with warfarin can occur.2
Over-the-counter sleep aids
Most over-the-counter sleep aids contain diphen-hydramine, a long-acting antihistamine that is considered less effective than benzodiazepines. The anticholinergic properties of antihistamines can result in cognitive changes and urinary retention in the elderly.8 Melatonin and valerian are “natural” hypnotics that are available without a prescription,9 but their safety and efficacy are not regulated by the FDA.8
Antidepressants
Antidepressants with sedative effects, such as tricyclic antidepressants and trazodone, have been used for insomnia, but minimal data support the efficacy or safety of this approach.8 Tricyclic antidepressants may exacerbate restless legs syndrome and periodic limb movement disorder,8 cause anticholinergic side effects, worsen chronic heart failure, and cause ortho-static hypotension and falls.2 Although tra-zodone is not a tricyclic antidepressant, it can cause dry mouth, orthostatic hypotension, and (rarely) priapism.2
Recommendations from others
A Canadian consensus statement published in 2003 supports the use of non-benzodiazepines such as zolpidem and zaleplon due to improved tolerability, and less withdrawal and abuse potential compared with benzodiazepines.7 The National Heart, Lung and Blood Institute Working Group on Insomnia recommends the use of short-acting hypnotics for short-term management of insomnia, but does not differentiate between short-acting benzodiazepines and the newer hypnotics such as zolpidem and zale-plon.8 Geriatric experts recommend that long-acting benzodiazepines, barbiturates, and amitriptyline be avoided in the elderly due to the risk of adverse drug events.10
Question the patient about sleep habits
David Cravens, MD, MSPH
Department of Family & Community Medicine, University of Missouri–Columbia
Sleep complaints are common in the elderly. However, before prescribing a hypnotic, determine the elderly patient’s sleep habits: often daytime naps plus nighttime sleep add up to adequate sleep. Encourage measures to avoid daytime naps if nighttime sleep is more important. Second, discuss sleep hygiene, such as avoiding evening caffeine or excessive alcohol, and avoiding using bed for activities other than sleeping, such as watching TV, reading, and the like. Determine whether sleep problems are part of a larger problem requiring evaluation, such as medication effects, depression, or obstructive sleep apnea. Finally, consider costs: although not a true hypnotic, trazodone at doses of 25–50 mg is a very effective and well-tolerated soporific at about one-tenth the cost of 5 mg of zolpidem or zaleplon.
Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines (strength of recommendation: B, based on extrapolations of randomized controlled trials). Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.
Evidence summary
Zolpidem and zaleplon
Zolpidem and zaleplon differ structurally from benzodiazepines but act at the benzodiazepine receptor.1 Due to their rapid absorption and short half-lives, they are particularly helpful for patients who have trouble falling asleep.2 They have been shown to decrease sleep latency, increase total sleep time, and increase sleep efficiency without disturbing sleep architecture or adversely affecting memory.1
Comparative studies in the elderly have demonstrated that zolpidem is as effective as triazolam,3 and that zaleplon is more effective than placebo at decreasing sleep latency and improving sleep quality.4 Tolerance, withdrawal symptoms, or rebound insomnia occur less frequently than with benzodi-azepines,1 but zolpidem increased risk of hip fracture in a case control study (adjusted odds ratio=1.95, 95% confidence interval, 1.09–3.51).5
Side effects of zolpidem and zaleplon are considered dose-related, and a lower dose of 5 mg is recommended for older patients.2 Efficacy of intermittent use of zolpidem has been demonstrated in clinical studies,1 a practice that could potentially decrease risk of side effects. Overall, if a hypnotic is desired for an older adult, zolpidem and zaleplon are preferred because of their improved side-effect profiles compared with older hypnotics such as benzodiazepines, chloral hydrate, over-the-counter sleep aids, and antidepressants (see Table ).
TABLE 1
Adverse effects of hypnotics in the elderly
| Hypnotic | Adverse effect |
|---|---|
| Benzodiazepines | Somnolence, anterograde amnesia, falls, hip fracture, rebound insomnia, tolerance, dependence, impaired sleep architecture2,3,5 |
| Antihistamines | Somnolence, dry mouth, constipation, urinary retention, blurred vision, cognitive changes3 |
| Valerian | Headache, excitability, uneasiness, cardiac disturbances, insomnia, drowsiness, withdrawal symptoms10 |
| Melatonin | Headache, depressive symptoms, daytime fatigue and drowsiness, dizziness, abdominal cramps, reduced alertness10 |
| Chloral hydrate | Nausea, vomiting, diarrhea, may increase effects of warfarin, overdose potential3,8 |
| Tricyclic antidepressants | Dry mouth, constipation, urinary retention, blurred vision, cognitive changes, orthostatic hypotension, somnolence, worsening of chronic heart failure, overdose potential, cardiac conduction abnormalities2,3 |
| Trazodone | Somnolence, orthostatic hypotension, dry mouth, priapism3 |
| Zolpidem | Drowsiness, headache, dizziness, somnolence, fatigue, agitation, nightmares, diarrhea, myalgia, arthralgia, anterograde amnesia1,10 |
| Zaleplon | Headache, dizziness, somnolence, short-term amnesic effects, next-day memory impairment, mild rebound insomnia1,10 |
Benzodiazepines
Benzodiazepines have been used since the 1960s for their hypnotic, anxiolytic, anticonvulsant, muscle-relaxing, and amnesic properties. A recent meta-analysis showed that benzodiazepines improve sleep latency by only 4.2 minutes compared with placebo.6 Although benzodiazepines increase sleep time and efficiency, patients quickly develop tolerance to the hypnotic effects.7 Additional problems associated with benzodiazepines include dependence, rebound insomnia, residual sedation, falls, hip fractures, and detrimental effects on sleep architecture.7
Chloral hydrate
Chloral hydrate has a narrow therapeutic index and is not recommended for the treatment of insomnia.8 Tolerance to its effects develops after only 2 weeks of use, and drug interactions with warfarin can occur.2
Over-the-counter sleep aids
Most over-the-counter sleep aids contain diphen-hydramine, a long-acting antihistamine that is considered less effective than benzodiazepines. The anticholinergic properties of antihistamines can result in cognitive changes and urinary retention in the elderly.8 Melatonin and valerian are “natural” hypnotics that are available without a prescription,9 but their safety and efficacy are not regulated by the FDA.8
Antidepressants
Antidepressants with sedative effects, such as tricyclic antidepressants and trazodone, have been used for insomnia, but minimal data support the efficacy or safety of this approach.8 Tricyclic antidepressants may exacerbate restless legs syndrome and periodic limb movement disorder,8 cause anticholinergic side effects, worsen chronic heart failure, and cause ortho-static hypotension and falls.2 Although tra-zodone is not a tricyclic antidepressant, it can cause dry mouth, orthostatic hypotension, and (rarely) priapism.2
Recommendations from others
A Canadian consensus statement published in 2003 supports the use of non-benzodiazepines such as zolpidem and zaleplon due to improved tolerability, and less withdrawal and abuse potential compared with benzodiazepines.7 The National Heart, Lung and Blood Institute Working Group on Insomnia recommends the use of short-acting hypnotics for short-term management of insomnia, but does not differentiate between short-acting benzodiazepines and the newer hypnotics such as zolpidem and zale-plon.8 Geriatric experts recommend that long-acting benzodiazepines, barbiturates, and amitriptyline be avoided in the elderly due to the risk of adverse drug events.10
Question the patient about sleep habits
David Cravens, MD, MSPH
Department of Family & Community Medicine, University of Missouri–Columbia
Sleep complaints are common in the elderly. However, before prescribing a hypnotic, determine the elderly patient’s sleep habits: often daytime naps plus nighttime sleep add up to adequate sleep. Encourage measures to avoid daytime naps if nighttime sleep is more important. Second, discuss sleep hygiene, such as avoiding evening caffeine or excessive alcohol, and avoiding using bed for activities other than sleeping, such as watching TV, reading, and the like. Determine whether sleep problems are part of a larger problem requiring evaluation, such as medication effects, depression, or obstructive sleep apnea. Finally, consider costs: although not a true hypnotic, trazodone at doses of 25–50 mg is a very effective and well-tolerated soporific at about one-tenth the cost of 5 mg of zolpidem or zaleplon.
1. Terzano MG, Rossi M, Palomba V, Smerien A, Parrino L. New drugs for insomnia: comparative tolerability of zopiclone, zolpi-dem and zaleplon. Drug Saf 2003;26:261-282.
2. McEvoy GK, Miller J, Litvak K, et al. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2003;2400-2405.
3. Roger M, Attali P, Coquelin JP. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993;15:127-136.
4. Hedner J, Yaeche R, Emilien G, Farr I, Salinas E. Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry 2000;15:704-712.
5. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avom J. Zolpidem use and hip fractures in older people. J Am Geriatr Soc 2001;49:1685-1690.
6. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162:225-233.
7. Montplaisir J, Hawa R, Moller H, et al. Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Hum Psychopharmacol 2003;18:29-38.
8. Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Institute Working Group on Insomnia. Am Fam Physician 1999;59:3029-3038.
9. Jellin JM, Gregory P, Batz F, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 3rd ed. Stockton, Calif: Therapeutic Research Faculty; 2000;723-7251052-1053.
10. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update. Arch Intern Med 1997;157:1531-1536.
1. Terzano MG, Rossi M, Palomba V, Smerien A, Parrino L. New drugs for insomnia: comparative tolerability of zopiclone, zolpi-dem and zaleplon. Drug Saf 2003;26:261-282.
2. McEvoy GK, Miller J, Litvak K, et al. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2003;2400-2405.
3. Roger M, Attali P, Coquelin JP. Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993;15:127-136.
4. Hedner J, Yaeche R, Emilien G, Farr I, Salinas E. Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry 2000;15:704-712.
5. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avom J. Zolpidem use and hip fractures in older people. J Am Geriatr Soc 2001;49:1685-1690.
6. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162:225-233.
7. Montplaisir J, Hawa R, Moller H, et al. Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Hum Psychopharmacol 2003;18:29-38.
8. Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Institute Working Group on Insomnia. Am Fam Physician 1999;59:3029-3038.
9. Jellin JM, Gregory P, Batz F, et al. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 3rd ed. Stockton, Calif: Therapeutic Research Faculty; 2000;723-7251052-1053.
10. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update. Arch Intern Med 1997;157:1531-1536.
Evidence-based answers from the Family Physicians Inquiries Network
What regimens eradicate Heliobacter pylori?
Fourteen-day triple therapy with a proton pump inhibitor (PPI) plus clarithromycin and either amoxicillin or metronidazole is superior to 7-day therapy in eradicating Heliobacter pylori (strength of recommendation [SOR]: A, high-quality meta-analysis).
Seven-day triple therapy with a PPI or ranitidine bismuth citrate plus clarithromycin and either amoxicillin or metronidazole is also effective (SOR: A, high-quality systematic review).
Three-day quadruple therapy with a combination of PPI, clarithromycin, bismuth subcitrate, and metronidazole or a combination of PPI, clarithromycin, amoxicillin, and metronidazole also appears to be effective (SOR: B, unblinded randomized controlled trial).
Evidence summary
The ideal H pylori eradication regimen should reach an intention-to-treat cure rate of 80% (Table).1 Effective regimens are:
Fourteen-day triple therapy of PPI + clarithromycin + metronidazole or amoxicillin. A meta-analysis of 13 studies found the eradication rate for 14-day therapy was 81% (95% confidence interval [CI], 77%–85%), compared with 72% (95% CI, 68%–76%) for 7-day therapy. The eradication rate for 10-day therapy (83%; 95% CI, 75%–89%), however, was not significantly better than that for 7-day therapy (80%; 95% CI, 71%–86%).2 Side effects were more frequent in the longer therapies, but did not lead to discontinuation of therapy.
Seven-day triple therapy of PPI + clarithromycin + metronidazole or amoxicillin. A high-quality systematic review of 82 studies using 7-day triple therapy found clarithromycin 500 twice daily yielded a higher eradication rate than clarithromycin 250 mg twice daily when combined with a PPI and amoxicillin (87% vs 81%; P<.0001). When clarithromycin was combined with a PPI and metronidazole, the higher dose of clarithromycin did not yield significantly higher eradication rates (88% vs 89%, P=.259).3
Seven-day triple therapy of ranitidine bismuth citrate + clarithromycin + metronidazole or amoxicillin. For these therapies, a high-quality systematic review of 8 studies reported eradication rates of 81% (95% CI, 77%–84%) with amoxicillin and 88% (95% CI, 85%–90%) with metronidazole.4,5 Side effects were not reported in a uniform manner for the 7-day therapies, but were noted to be mild and did not lead to significant discontinuation of therapy. Pooled dropout rates were similar among all regimens.4
Three-day quadruple therapy of PPI + bismuth + clarithromycin + metronidazole or PPI+ clarithromycin + amoxicillin + metronidazole. An otherwise high-quality but unblinded randomized clinical trial of 234 patients demonstrated that 2 days of pretreatment with lansoprazole followed by 3 days of lansoprazole with clarithromycin, amoxicillin, and metronidazole yielded eradication rates comparable with 5-day treatment (81% vs. 89%; P<.05).6
Another randomized clinical trial of 118 patients, blinded to investigators but not patients, showed that quadruple 3-day therapy with lansoprazole + bismuth + clarithromycin + metronidazole was as effective as 7 days of lansoprazole + clarithromycin + metronidazole (87% vs 86%; P=.94), and had significantly shorter duration of side effects (2.6 vs 6.2 days; P<.001). Eradication rates were similar in isolates that were resistant or sensitive to either metronidazole or clarithromycin.7
The problems of emerging clarithromycin and metronidazole resistance have not been
extensively studied. In 1 review, metronida-zole-containing regimens eradicated metronidazole-sensitive strains more effectively than metronidazole-resistant strains (weighted difference, 15%; 95% CI, 8%–20%).4 When an infection is resistant to metronidazole, amoxicillin should be used instead.4 In areas of high clarithromycin and metronidazole resistance, a quadruple regimen might be more effective.7
TABLE
Effective therapies for Heliobacter pylorieradication
| Regimen | Dosage | Duration (days) | Cost ($)b | SOR |
|---|---|---|---|---|
| PPIa | 14 | 210 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 500 mg twice daily or | |||
| amoxicillin | 1000 mg twice daily | |||
| PPI | 7 | 105 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| PPI | 7 | 105 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 500 mg twice daily | |||
| Ranitidine bismuth citrate | 400 mg twice daily | 7 | 85 | A |
| Clarithromycin | 500 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| Ranitidine bismuth citrate | 400 mg twice daily | 7 | 82 | A |
| Clarithromycin | 250 mg twice daily | |||
| Metronidazole | 500 mg twice daily | |||
| PPI | 3 | 46 | B | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 400 mg twice daily | |||
| Bismuth subcitrate | 240 mg twice daily | |||
| PPI (5 days) | 3 | 60 | B | |
| Clarithromycin | 250 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| Metronidazole | 400 mg twice daily | |||
| a. PPI: standard twice-daily dosing—eg, lansoprazole 30 mg or omeprazole 20 mg | ||||
| b. Approximate cost of entire course of therapy from www.drugstore.com, August 2003. | ||||
| PPI, proton pump inhibitor; SOR, strength of recommendation (for an explanation of evidence ratings, see page 779) | ||||
Recommendations from others
The Maastricht Consensus of the European Heliobacter Study Group1 recommends a 7-day triple regimen of PPI + clarithromycin + either metronidazole or amoxicillin or (if clarithromycin resistance is prevalent) PPI + amoxicillin 500 mg 3 times daily + metronidazole 500 mg 3 times daily.
The American College of Gastroenterology recommends 14-day therapy of one of the following options:8
- PPI + clarithromycin + (metronidazole or amoxicillin), or ranitidine bismuth citrate + clarithromycin + (metronidazole or amoxicillin). Tetracycline 500 mg twice a day can be substituted for amoxicillin or metronidazole
- PPI + bismuth subsalicylate 525 mg + metronidazole 500 mg 3 times daily + tetra-cycline 500 mg 4 times daily
- Bismuth subsalicylate 525 mg 4 times daily + metronidazole 250 mg 4 times daily + tetra-cycline 500 mg 4 times daily + H2 receptor antagonist in standard acid-suppression dose (eg, famotidine 20 mg twice a day for 4 weeks).
The Institute for Clinical Systems Improvement recommends as first-choice treatment a 7-day PPI/clarithromycin/amoxicillin combination, and as second choice a 7-day regimen of PPI, tetracycline 250 mg 4 times daily, metronidazole 500 mg twice daily, and bismuth subsalicylate 525 mg 4 times daily.9
Patients beginning complex regimens require counseling
Laura B. Hansen, PharmD, BCPS
University of Colorado Health Sciences Center, Denver, Colorado
The most effective regimens (>80% eradication) for H pylori include a 10- to 14-day course of at least 2 antibiotics and an antisecretory agent. However, even optimal treatment regimens can fail in approximately 10% of patients. Poor compliance is among the most common reasons for treatment failure. Medication side effects can affect up to 50% of patients taking triple-agent regimens.
Treatment regimens with multiple medications administered several times daily can be difficult to follow. Convenient packaging containing all daily medications are available to optimize adherence.
Counseling points for patients should include how to take the medicine correctly, expected side effects, the importance of completing the entire therapy regimen, and warnings of specific interactions (eg, alcohol and metronidazole). Lastly, the patient should be made aware of the cost of the entire regimen, which ranges from $50 to $250.
1. Current European concepts in the management of Heliobacter pylori infection. The Maastricht Consensus Report. European Heliobacter Pylori Study Group. Gut 1997;41:8-13.
2. Calvet X, Garcia N, Lopez T, Gisbert JP, Gene E, Roque M. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxicillin for treating Heliobacter pylori infection. Aliment Pharmacol Ther 2000;14:603-609.
3. Huang J, Hunt RH. The importance of clarithromycin dose in the management of Heliobacter pylori infection: a meta-analysis of triple therapies with a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. Aliment Pharmacol Ther 1999;13:719-729.
4. Janssen MJ, Van Oijen AH, Verbeek AL, Jansen JB, De Boer WA. A systematic comparison of triple therapies for treatment of Heliobacter pylori infection with proton pump inhibitor/ranitidine bismuth citrate plus clarithromycin and either amoxicillin or a nitroimidazole. Aliment Pharmacol Ther 2001;15:613-624.
5. Delaney B, Moayyedi P, Forman D. Heliobacter pylori. Clin Evid [online], Issue 8. London: BMJ Publishing Group, Last updated 2003 March. Available at www.ovid.com. Accessed on March 4, 2003.
6. Treiber G, Wittig J, Ammon S, Walker S, van Doorn LJ, Klotz U. Clinical outcome and influencing factors for a new short-term quadruple therapy for Heliobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med. 2002;162:153-160.
7. Wong BC, Wang WH, Wong WM, et al. Three-day lansoprazole quadruple therapy for Heliobacter pylori-positive duodenal ulcers: a randomized controlled study. Aliment PharmacTher 2001;15:843-849.
8. Howden CW, Hunt RH. Guidelines for the management of Heliobacter pylori infection. Ad Hoc Committee on the Practice Parameters of the American College of Gastroenterology. Am J Gastroenterol 1998;93:2330-2338.
9. Institute for Clinical Systems Improvement (ICSI). Dyspepsia. Bloomington, Minn: ICSI; last updated January 2003. Available at: http://www.icsi.org/ knowledge/detail.asp?catID=29&itemID=171. Accessed on September 8, 2003.
Fourteen-day triple therapy with a proton pump inhibitor (PPI) plus clarithromycin and either amoxicillin or metronidazole is superior to 7-day therapy in eradicating Heliobacter pylori (strength of recommendation [SOR]: A, high-quality meta-analysis).
Seven-day triple therapy with a PPI or ranitidine bismuth citrate plus clarithromycin and either amoxicillin or metronidazole is also effective (SOR: A, high-quality systematic review).
Three-day quadruple therapy with a combination of PPI, clarithromycin, bismuth subcitrate, and metronidazole or a combination of PPI, clarithromycin, amoxicillin, and metronidazole also appears to be effective (SOR: B, unblinded randomized controlled trial).
Evidence summary
The ideal H pylori eradication regimen should reach an intention-to-treat cure rate of 80% (Table).1 Effective regimens are:
Fourteen-day triple therapy of PPI + clarithromycin + metronidazole or amoxicillin. A meta-analysis of 13 studies found the eradication rate for 14-day therapy was 81% (95% confidence interval [CI], 77%–85%), compared with 72% (95% CI, 68%–76%) for 7-day therapy. The eradication rate for 10-day therapy (83%; 95% CI, 75%–89%), however, was not significantly better than that for 7-day therapy (80%; 95% CI, 71%–86%).2 Side effects were more frequent in the longer therapies, but did not lead to discontinuation of therapy.
Seven-day triple therapy of PPI + clarithromycin + metronidazole or amoxicillin. A high-quality systematic review of 82 studies using 7-day triple therapy found clarithromycin 500 twice daily yielded a higher eradication rate than clarithromycin 250 mg twice daily when combined with a PPI and amoxicillin (87% vs 81%; P<.0001). When clarithromycin was combined with a PPI and metronidazole, the higher dose of clarithromycin did not yield significantly higher eradication rates (88% vs 89%, P=.259).3
Seven-day triple therapy of ranitidine bismuth citrate + clarithromycin + metronidazole or amoxicillin. For these therapies, a high-quality systematic review of 8 studies reported eradication rates of 81% (95% CI, 77%–84%) with amoxicillin and 88% (95% CI, 85%–90%) with metronidazole.4,5 Side effects were not reported in a uniform manner for the 7-day therapies, but were noted to be mild and did not lead to significant discontinuation of therapy. Pooled dropout rates were similar among all regimens.4
Three-day quadruple therapy of PPI + bismuth + clarithromycin + metronidazole or PPI+ clarithromycin + amoxicillin + metronidazole. An otherwise high-quality but unblinded randomized clinical trial of 234 patients demonstrated that 2 days of pretreatment with lansoprazole followed by 3 days of lansoprazole with clarithromycin, amoxicillin, and metronidazole yielded eradication rates comparable with 5-day treatment (81% vs. 89%; P<.05).6
Another randomized clinical trial of 118 patients, blinded to investigators but not patients, showed that quadruple 3-day therapy with lansoprazole + bismuth + clarithromycin + metronidazole was as effective as 7 days of lansoprazole + clarithromycin + metronidazole (87% vs 86%; P=.94), and had significantly shorter duration of side effects (2.6 vs 6.2 days; P<.001). Eradication rates were similar in isolates that were resistant or sensitive to either metronidazole or clarithromycin.7
The problems of emerging clarithromycin and metronidazole resistance have not been
extensively studied. In 1 review, metronida-zole-containing regimens eradicated metronidazole-sensitive strains more effectively than metronidazole-resistant strains (weighted difference, 15%; 95% CI, 8%–20%).4 When an infection is resistant to metronidazole, amoxicillin should be used instead.4 In areas of high clarithromycin and metronidazole resistance, a quadruple regimen might be more effective.7
TABLE
Effective therapies for Heliobacter pylorieradication
| Regimen | Dosage | Duration (days) | Cost ($)b | SOR |
|---|---|---|---|---|
| PPIa | 14 | 210 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 500 mg twice daily or | |||
| amoxicillin | 1000 mg twice daily | |||
| PPI | 7 | 105 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| PPI | 7 | 105 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 500 mg twice daily | |||
| Ranitidine bismuth citrate | 400 mg twice daily | 7 | 85 | A |
| Clarithromycin | 500 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| Ranitidine bismuth citrate | 400 mg twice daily | 7 | 82 | A |
| Clarithromycin | 250 mg twice daily | |||
| Metronidazole | 500 mg twice daily | |||
| PPI | 3 | 46 | B | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 400 mg twice daily | |||
| Bismuth subcitrate | 240 mg twice daily | |||
| PPI (5 days) | 3 | 60 | B | |
| Clarithromycin | 250 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| Metronidazole | 400 mg twice daily | |||
| a. PPI: standard twice-daily dosing—eg, lansoprazole 30 mg or omeprazole 20 mg | ||||
| b. Approximate cost of entire course of therapy from www.drugstore.com, August 2003. | ||||
| PPI, proton pump inhibitor; SOR, strength of recommendation (for an explanation of evidence ratings, see page 779) | ||||
Recommendations from others
The Maastricht Consensus of the European Heliobacter Study Group1 recommends a 7-day triple regimen of PPI + clarithromycin + either metronidazole or amoxicillin or (if clarithromycin resistance is prevalent) PPI + amoxicillin 500 mg 3 times daily + metronidazole 500 mg 3 times daily.
The American College of Gastroenterology recommends 14-day therapy of one of the following options:8
- PPI + clarithromycin + (metronidazole or amoxicillin), or ranitidine bismuth citrate + clarithromycin + (metronidazole or amoxicillin). Tetracycline 500 mg twice a day can be substituted for amoxicillin or metronidazole
- PPI + bismuth subsalicylate 525 mg + metronidazole 500 mg 3 times daily + tetra-cycline 500 mg 4 times daily
- Bismuth subsalicylate 525 mg 4 times daily + metronidazole 250 mg 4 times daily + tetra-cycline 500 mg 4 times daily + H2 receptor antagonist in standard acid-suppression dose (eg, famotidine 20 mg twice a day for 4 weeks).
The Institute for Clinical Systems Improvement recommends as first-choice treatment a 7-day PPI/clarithromycin/amoxicillin combination, and as second choice a 7-day regimen of PPI, tetracycline 250 mg 4 times daily, metronidazole 500 mg twice daily, and bismuth subsalicylate 525 mg 4 times daily.9
Patients beginning complex regimens require counseling
Laura B. Hansen, PharmD, BCPS
University of Colorado Health Sciences Center, Denver, Colorado
The most effective regimens (>80% eradication) for H pylori include a 10- to 14-day course of at least 2 antibiotics and an antisecretory agent. However, even optimal treatment regimens can fail in approximately 10% of patients. Poor compliance is among the most common reasons for treatment failure. Medication side effects can affect up to 50% of patients taking triple-agent regimens.
Treatment regimens with multiple medications administered several times daily can be difficult to follow. Convenient packaging containing all daily medications are available to optimize adherence.
Counseling points for patients should include how to take the medicine correctly, expected side effects, the importance of completing the entire therapy regimen, and warnings of specific interactions (eg, alcohol and metronidazole). Lastly, the patient should be made aware of the cost of the entire regimen, which ranges from $50 to $250.
Fourteen-day triple therapy with a proton pump inhibitor (PPI) plus clarithromycin and either amoxicillin or metronidazole is superior to 7-day therapy in eradicating Heliobacter pylori (strength of recommendation [SOR]: A, high-quality meta-analysis).
Seven-day triple therapy with a PPI or ranitidine bismuth citrate plus clarithromycin and either amoxicillin or metronidazole is also effective (SOR: A, high-quality systematic review).
Three-day quadruple therapy with a combination of PPI, clarithromycin, bismuth subcitrate, and metronidazole or a combination of PPI, clarithromycin, amoxicillin, and metronidazole also appears to be effective (SOR: B, unblinded randomized controlled trial).
Evidence summary
The ideal H pylori eradication regimen should reach an intention-to-treat cure rate of 80% (Table).1 Effective regimens are:
Fourteen-day triple therapy of PPI + clarithromycin + metronidazole or amoxicillin. A meta-analysis of 13 studies found the eradication rate for 14-day therapy was 81% (95% confidence interval [CI], 77%–85%), compared with 72% (95% CI, 68%–76%) for 7-day therapy. The eradication rate for 10-day therapy (83%; 95% CI, 75%–89%), however, was not significantly better than that for 7-day therapy (80%; 95% CI, 71%–86%).2 Side effects were more frequent in the longer therapies, but did not lead to discontinuation of therapy.
Seven-day triple therapy of PPI + clarithromycin + metronidazole or amoxicillin. A high-quality systematic review of 82 studies using 7-day triple therapy found clarithromycin 500 twice daily yielded a higher eradication rate than clarithromycin 250 mg twice daily when combined with a PPI and amoxicillin (87% vs 81%; P<.0001). When clarithromycin was combined with a PPI and metronidazole, the higher dose of clarithromycin did not yield significantly higher eradication rates (88% vs 89%, P=.259).3
Seven-day triple therapy of ranitidine bismuth citrate + clarithromycin + metronidazole or amoxicillin. For these therapies, a high-quality systematic review of 8 studies reported eradication rates of 81% (95% CI, 77%–84%) with amoxicillin and 88% (95% CI, 85%–90%) with metronidazole.4,5 Side effects were not reported in a uniform manner for the 7-day therapies, but were noted to be mild and did not lead to significant discontinuation of therapy. Pooled dropout rates were similar among all regimens.4
Three-day quadruple therapy of PPI + bismuth + clarithromycin + metronidazole or PPI+ clarithromycin + amoxicillin + metronidazole. An otherwise high-quality but unblinded randomized clinical trial of 234 patients demonstrated that 2 days of pretreatment with lansoprazole followed by 3 days of lansoprazole with clarithromycin, amoxicillin, and metronidazole yielded eradication rates comparable with 5-day treatment (81% vs. 89%; P<.05).6
Another randomized clinical trial of 118 patients, blinded to investigators but not patients, showed that quadruple 3-day therapy with lansoprazole + bismuth + clarithromycin + metronidazole was as effective as 7 days of lansoprazole + clarithromycin + metronidazole (87% vs 86%; P=.94), and had significantly shorter duration of side effects (2.6 vs 6.2 days; P<.001). Eradication rates were similar in isolates that were resistant or sensitive to either metronidazole or clarithromycin.7
The problems of emerging clarithromycin and metronidazole resistance have not been
extensively studied. In 1 review, metronida-zole-containing regimens eradicated metronidazole-sensitive strains more effectively than metronidazole-resistant strains (weighted difference, 15%; 95% CI, 8%–20%).4 When an infection is resistant to metronidazole, amoxicillin should be used instead.4 In areas of high clarithromycin and metronidazole resistance, a quadruple regimen might be more effective.7
TABLE
Effective therapies for Heliobacter pylorieradication
| Regimen | Dosage | Duration (days) | Cost ($)b | SOR |
|---|---|---|---|---|
| PPIa | 14 | 210 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 500 mg twice daily or | |||
| amoxicillin | 1000 mg twice daily | |||
| PPI | 7 | 105 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| PPI | 7 | 105 | A | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 500 mg twice daily | |||
| Ranitidine bismuth citrate | 400 mg twice daily | 7 | 85 | A |
| Clarithromycin | 500 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| Ranitidine bismuth citrate | 400 mg twice daily | 7 | 82 | A |
| Clarithromycin | 250 mg twice daily | |||
| Metronidazole | 500 mg twice daily | |||
| PPI | 3 | 46 | B | |
| Clarithromycin | 500 mg twice daily | |||
| Metronidazole | 400 mg twice daily | |||
| Bismuth subcitrate | 240 mg twice daily | |||
| PPI (5 days) | 3 | 60 | B | |
| Clarithromycin | 250 mg twice daily | |||
| Amoxicillin | 1000 mg twice daily | |||
| Metronidazole | 400 mg twice daily | |||
| a. PPI: standard twice-daily dosing—eg, lansoprazole 30 mg or omeprazole 20 mg | ||||
| b. Approximate cost of entire course of therapy from www.drugstore.com, August 2003. | ||||
| PPI, proton pump inhibitor; SOR, strength of recommendation (for an explanation of evidence ratings, see page 779) | ||||
Recommendations from others
The Maastricht Consensus of the European Heliobacter Study Group1 recommends a 7-day triple regimen of PPI + clarithromycin + either metronidazole or amoxicillin or (if clarithromycin resistance is prevalent) PPI + amoxicillin 500 mg 3 times daily + metronidazole 500 mg 3 times daily.
The American College of Gastroenterology recommends 14-day therapy of one of the following options:8
- PPI + clarithromycin + (metronidazole or amoxicillin), or ranitidine bismuth citrate + clarithromycin + (metronidazole or amoxicillin). Tetracycline 500 mg twice a day can be substituted for amoxicillin or metronidazole
- PPI + bismuth subsalicylate 525 mg + metronidazole 500 mg 3 times daily + tetra-cycline 500 mg 4 times daily
- Bismuth subsalicylate 525 mg 4 times daily + metronidazole 250 mg 4 times daily + tetra-cycline 500 mg 4 times daily + H2 receptor antagonist in standard acid-suppression dose (eg, famotidine 20 mg twice a day for 4 weeks).
The Institute for Clinical Systems Improvement recommends as first-choice treatment a 7-day PPI/clarithromycin/amoxicillin combination, and as second choice a 7-day regimen of PPI, tetracycline 250 mg 4 times daily, metronidazole 500 mg twice daily, and bismuth subsalicylate 525 mg 4 times daily.9
Patients beginning complex regimens require counseling
Laura B. Hansen, PharmD, BCPS
University of Colorado Health Sciences Center, Denver, Colorado
The most effective regimens (>80% eradication) for H pylori include a 10- to 14-day course of at least 2 antibiotics and an antisecretory agent. However, even optimal treatment regimens can fail in approximately 10% of patients. Poor compliance is among the most common reasons for treatment failure. Medication side effects can affect up to 50% of patients taking triple-agent regimens.
Treatment regimens with multiple medications administered several times daily can be difficult to follow. Convenient packaging containing all daily medications are available to optimize adherence.
Counseling points for patients should include how to take the medicine correctly, expected side effects, the importance of completing the entire therapy regimen, and warnings of specific interactions (eg, alcohol and metronidazole). Lastly, the patient should be made aware of the cost of the entire regimen, which ranges from $50 to $250.
1. Current European concepts in the management of Heliobacter pylori infection. The Maastricht Consensus Report. European Heliobacter Pylori Study Group. Gut 1997;41:8-13.
2. Calvet X, Garcia N, Lopez T, Gisbert JP, Gene E, Roque M. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxicillin for treating Heliobacter pylori infection. Aliment Pharmacol Ther 2000;14:603-609.
3. Huang J, Hunt RH. The importance of clarithromycin dose in the management of Heliobacter pylori infection: a meta-analysis of triple therapies with a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. Aliment Pharmacol Ther 1999;13:719-729.
4. Janssen MJ, Van Oijen AH, Verbeek AL, Jansen JB, De Boer WA. A systematic comparison of triple therapies for treatment of Heliobacter pylori infection with proton pump inhibitor/ranitidine bismuth citrate plus clarithromycin and either amoxicillin or a nitroimidazole. Aliment Pharmacol Ther 2001;15:613-624.
5. Delaney B, Moayyedi P, Forman D. Heliobacter pylori. Clin Evid [online], Issue 8. London: BMJ Publishing Group, Last updated 2003 March. Available at www.ovid.com. Accessed on March 4, 2003.
6. Treiber G, Wittig J, Ammon S, Walker S, van Doorn LJ, Klotz U. Clinical outcome and influencing factors for a new short-term quadruple therapy for Heliobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med. 2002;162:153-160.
7. Wong BC, Wang WH, Wong WM, et al. Three-day lansoprazole quadruple therapy for Heliobacter pylori-positive duodenal ulcers: a randomized controlled study. Aliment PharmacTher 2001;15:843-849.
8. Howden CW, Hunt RH. Guidelines for the management of Heliobacter pylori infection. Ad Hoc Committee on the Practice Parameters of the American College of Gastroenterology. Am J Gastroenterol 1998;93:2330-2338.
9. Institute for Clinical Systems Improvement (ICSI). Dyspepsia. Bloomington, Minn: ICSI; last updated January 2003. Available at: http://www.icsi.org/ knowledge/detail.asp?catID=29&itemID=171. Accessed on September 8, 2003.
1. Current European concepts in the management of Heliobacter pylori infection. The Maastricht Consensus Report. European Heliobacter Pylori Study Group. Gut 1997;41:8-13.
2. Calvet X, Garcia N, Lopez T, Gisbert JP, Gene E, Roque M. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxicillin for treating Heliobacter pylori infection. Aliment Pharmacol Ther 2000;14:603-609.
3. Huang J, Hunt RH. The importance of clarithromycin dose in the management of Heliobacter pylori infection: a meta-analysis of triple therapies with a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole. Aliment Pharmacol Ther 1999;13:719-729.
4. Janssen MJ, Van Oijen AH, Verbeek AL, Jansen JB, De Boer WA. A systematic comparison of triple therapies for treatment of Heliobacter pylori infection with proton pump inhibitor/ranitidine bismuth citrate plus clarithromycin and either amoxicillin or a nitroimidazole. Aliment Pharmacol Ther 2001;15:613-624.
5. Delaney B, Moayyedi P, Forman D. Heliobacter pylori. Clin Evid [online], Issue 8. London: BMJ Publishing Group, Last updated 2003 March. Available at www.ovid.com. Accessed on March 4, 2003.
6. Treiber G, Wittig J, Ammon S, Walker S, van Doorn LJ, Klotz U. Clinical outcome and influencing factors for a new short-term quadruple therapy for Heliobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med. 2002;162:153-160.
7. Wong BC, Wang WH, Wong WM, et al. Three-day lansoprazole quadruple therapy for Heliobacter pylori-positive duodenal ulcers: a randomized controlled study. Aliment PharmacTher 2001;15:843-849.
8. Howden CW, Hunt RH. Guidelines for the management of Heliobacter pylori infection. Ad Hoc Committee on the Practice Parameters of the American College of Gastroenterology. Am J Gastroenterol 1998;93:2330-2338.
9. Institute for Clinical Systems Improvement (ICSI). Dyspepsia. Bloomington, Minn: ICSI; last updated January 2003. Available at: http://www.icsi.org/ knowledge/detail.asp?catID=29&itemID=171. Accessed on September 8, 2003.
Evidence-based answers from the Family Physicians Inquiries Network