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Do antibiotics improve outcomes for patients hospitalized with COPD exacerbations?
YES. Antibiotic use reduced mortality and treatment failure in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (COPD) (strength of recommendation [SOR]: A, systematic reviews of randomized controlled trials [RCTs]).
Giving antibiotics early to hospitalized patients decreased the need for later ventilation and readmission within 30 days for exacerbation of COPD (SOR: B, a retrospective cohort study).
Evidence summary
A systematic review of 4 RCTs with a total of 356 patients found that antibiotic therapy reduced mortality more than placebo in moderately to severely ill hospitalized patients with COPD. Short-term mortality (7 days after treatment to 18 months after hospital discharge) decreased by 77% with antibiotic use in acute exacerbations of COPD (number needed to treat [NNT]=8; 95% confidence interval [CI], 6-17).
This same Cochrane review and a meta-analysis of 4 hospital-based trials with 321 patients evaluated failure to improve, deterioration, or death during the study period.1,2 The results favored treatment with antibiotics over placebo (NNT=3; 95% CI, 3-5).
Don’t wait to give antibiotics
A large retrospective cohort study of 84,621 hospitalized patients compared outcomes in patients given antibiotics for acute exacerbations of COPD during their first 2 days in the hospital with patients treated later or not at all.3 Outcomes assessed included need for later ventilation and readmission within 30 days for acute exacerbations of COPD.
The study included patients 40 years or older with a principal diagnosis, based on ICD 9 codes, of acute exacerbation of COPD, emphysema, or respiratory failure paired with a secondary diagnosis of COPD with acute exacerbation or emphysema. Patients who had been admitted directly to the intensive care unit were excluded, as were patients with other bacterial infections, such as pneumonia or cellulitis, for which they might receive antibiotics.
Early administration of antibiotics delayed the need for subsequent ventilation when compared with no antibiotics or antibiotics given later (1.07% vs 1.80%; P<.001; NNT=137). Giving antibiotics early also lowered readmission rates for acute exacerbations of COPD (7.91% vs 8.79%; P<.001; NNT=114), improved mortality rates (1.04% vs 1.59%; P<.001; NNT=182), and decreased treatment failure (9.77% vs 11.75%; P<.001; NNT=51).
Recommendations
The recommendations of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), updated in 2008, call for antibiotics to be given to patients with 2 or more of the cardinal symptoms of acute exacerbations of COPD (shortness of breath, increased sputum production, and sputum purulence). Patients with severe exacerbations who require a ventilator should also receive antibiotics.4
The Primary Care Consensus Guidelines from 2004, consistent with the GOLD recommendations, state that a newer macrolide, extended-spectrum cephalosporin, or doxycycline is appropriate for moderately severe exacerbations. High-dose amoxicillin/clavulanate or a respiratory fluoroquinolone should be given for severe exacerbations.5
1. Ram FSF, Rodriguez-Rosin R, Granados-Navarrete A, et al. Antibiotics for exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;(2):CD004403.
2. Russo RL, D’Aprile M. Role of antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease. Ann Pharmacother. 2001;35:576-581.
3. Rothenberg M, Pekow P, Lahti M, et al. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA. 2010;303:2035-2042.
4. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. NHLBI/WHO workshop report. Bethesda, Md: National Heart, Lung and Blood Institute; April 2001. Updated December 2009. Available at: http://www.goldcopd.com. Accessed July 1, 2011.
5. Brunton S, Carmichael P, Colgan R, et al. Acute exacerbation of chronic bronchitis: a primary care consensus guideline. Am J Manag Care. 2004;10:689-696.
YES. Antibiotic use reduced mortality and treatment failure in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (COPD) (strength of recommendation [SOR]: A, systematic reviews of randomized controlled trials [RCTs]).
Giving antibiotics early to hospitalized patients decreased the need for later ventilation and readmission within 30 days for exacerbation of COPD (SOR: B, a retrospective cohort study).
Evidence summary
A systematic review of 4 RCTs with a total of 356 patients found that antibiotic therapy reduced mortality more than placebo in moderately to severely ill hospitalized patients with COPD. Short-term mortality (7 days after treatment to 18 months after hospital discharge) decreased by 77% with antibiotic use in acute exacerbations of COPD (number needed to treat [NNT]=8; 95% confidence interval [CI], 6-17).
This same Cochrane review and a meta-analysis of 4 hospital-based trials with 321 patients evaluated failure to improve, deterioration, or death during the study period.1,2 The results favored treatment with antibiotics over placebo (NNT=3; 95% CI, 3-5).
Don’t wait to give antibiotics
A large retrospective cohort study of 84,621 hospitalized patients compared outcomes in patients given antibiotics for acute exacerbations of COPD during their first 2 days in the hospital with patients treated later or not at all.3 Outcomes assessed included need for later ventilation and readmission within 30 days for acute exacerbations of COPD.
The study included patients 40 years or older with a principal diagnosis, based on ICD 9 codes, of acute exacerbation of COPD, emphysema, or respiratory failure paired with a secondary diagnosis of COPD with acute exacerbation or emphysema. Patients who had been admitted directly to the intensive care unit were excluded, as were patients with other bacterial infections, such as pneumonia or cellulitis, for which they might receive antibiotics.
Early administration of antibiotics delayed the need for subsequent ventilation when compared with no antibiotics or antibiotics given later (1.07% vs 1.80%; P<.001; NNT=137). Giving antibiotics early also lowered readmission rates for acute exacerbations of COPD (7.91% vs 8.79%; P<.001; NNT=114), improved mortality rates (1.04% vs 1.59%; P<.001; NNT=182), and decreased treatment failure (9.77% vs 11.75%; P<.001; NNT=51).
Recommendations
The recommendations of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), updated in 2008, call for antibiotics to be given to patients with 2 or more of the cardinal symptoms of acute exacerbations of COPD (shortness of breath, increased sputum production, and sputum purulence). Patients with severe exacerbations who require a ventilator should also receive antibiotics.4
The Primary Care Consensus Guidelines from 2004, consistent with the GOLD recommendations, state that a newer macrolide, extended-spectrum cephalosporin, or doxycycline is appropriate for moderately severe exacerbations. High-dose amoxicillin/clavulanate or a respiratory fluoroquinolone should be given for severe exacerbations.5
YES. Antibiotic use reduced mortality and treatment failure in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (COPD) (strength of recommendation [SOR]: A, systematic reviews of randomized controlled trials [RCTs]).
Giving antibiotics early to hospitalized patients decreased the need for later ventilation and readmission within 30 days for exacerbation of COPD (SOR: B, a retrospective cohort study).
Evidence summary
A systematic review of 4 RCTs with a total of 356 patients found that antibiotic therapy reduced mortality more than placebo in moderately to severely ill hospitalized patients with COPD. Short-term mortality (7 days after treatment to 18 months after hospital discharge) decreased by 77% with antibiotic use in acute exacerbations of COPD (number needed to treat [NNT]=8; 95% confidence interval [CI], 6-17).
This same Cochrane review and a meta-analysis of 4 hospital-based trials with 321 patients evaluated failure to improve, deterioration, or death during the study period.1,2 The results favored treatment with antibiotics over placebo (NNT=3; 95% CI, 3-5).
Don’t wait to give antibiotics
A large retrospective cohort study of 84,621 hospitalized patients compared outcomes in patients given antibiotics for acute exacerbations of COPD during their first 2 days in the hospital with patients treated later or not at all.3 Outcomes assessed included need for later ventilation and readmission within 30 days for acute exacerbations of COPD.
The study included patients 40 years or older with a principal diagnosis, based on ICD 9 codes, of acute exacerbation of COPD, emphysema, or respiratory failure paired with a secondary diagnosis of COPD with acute exacerbation or emphysema. Patients who had been admitted directly to the intensive care unit were excluded, as were patients with other bacterial infections, such as pneumonia or cellulitis, for which they might receive antibiotics.
Early administration of antibiotics delayed the need for subsequent ventilation when compared with no antibiotics or antibiotics given later (1.07% vs 1.80%; P<.001; NNT=137). Giving antibiotics early also lowered readmission rates for acute exacerbations of COPD (7.91% vs 8.79%; P<.001; NNT=114), improved mortality rates (1.04% vs 1.59%; P<.001; NNT=182), and decreased treatment failure (9.77% vs 11.75%; P<.001; NNT=51).
Recommendations
The recommendations of the Global Initiative for Chronic Obstructive Lung Disease (GOLD), updated in 2008, call for antibiotics to be given to patients with 2 or more of the cardinal symptoms of acute exacerbations of COPD (shortness of breath, increased sputum production, and sputum purulence). Patients with severe exacerbations who require a ventilator should also receive antibiotics.4
The Primary Care Consensus Guidelines from 2004, consistent with the GOLD recommendations, state that a newer macrolide, extended-spectrum cephalosporin, or doxycycline is appropriate for moderately severe exacerbations. High-dose amoxicillin/clavulanate or a respiratory fluoroquinolone should be given for severe exacerbations.5
1. Ram FSF, Rodriguez-Rosin R, Granados-Navarrete A, et al. Antibiotics for exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;(2):CD004403.
2. Russo RL, D’Aprile M. Role of antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease. Ann Pharmacother. 2001;35:576-581.
3. Rothenberg M, Pekow P, Lahti M, et al. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA. 2010;303:2035-2042.
4. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. NHLBI/WHO workshop report. Bethesda, Md: National Heart, Lung and Blood Institute; April 2001. Updated December 2009. Available at: http://www.goldcopd.com. Accessed July 1, 2011.
5. Brunton S, Carmichael P, Colgan R, et al. Acute exacerbation of chronic bronchitis: a primary care consensus guideline. Am J Manag Care. 2004;10:689-696.
1. Ram FSF, Rodriguez-Rosin R, Granados-Navarrete A, et al. Antibiotics for exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;(2):CD004403.
2. Russo RL, D’Aprile M. Role of antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease. Ann Pharmacother. 2001;35:576-581.
3. Rothenberg M, Pekow P, Lahti M, et al. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA. 2010;303:2035-2042.
4. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. NHLBI/WHO workshop report. Bethesda, Md: National Heart, Lung and Blood Institute; April 2001. Updated December 2009. Available at: http://www.goldcopd.com. Accessed July 1, 2011.
5. Brunton S, Carmichael P, Colgan R, et al. Acute exacerbation of chronic bronchitis: a primary care consensus guideline. Am J Manag Care. 2004;10:689-696.
Evidence-based answers from the Family Physicians Inquiries Network
What’s the best way to control circumcision pain in newborns?
DORSAL PENILE NERVE BLOCK (DPNB), ring block (RB), and eutectic mixture of local anesthetics (EMLA) all control pain effectively during neonatal circumcision (strength of recommendation [SOR]: A, systematic review). An RB may provide superior pain relief to DPNB and EMLA (SOR: B, limited-quality evidence).
Using a Mogen clamp reduces pain by shortening procedure time (SOR: A, randomized controlled trials [RCTs]). Effective adjuncts to pain relief include nonnutritive sucking (NNS; a pacifier without sucrose), a sucrose pacifier, and use of a padded chair (SOR: A, RCTs).
Evidence summary
Outcome assessment of neonatal pain response includes heart rate, crying time, procedure length, and behavioral distress scores. A Cochrane systematic review of 35 RCTs with a total of 1997 newborns evaluated DPNB, RB, and EMLA for pain relief during circumcision.1 All 3 methods were more effective than placebo or no treatment. Studies of DPNB reported lowered heart rates and shorter crying times than studies with EMLA vs placebo and RB vs placebo (TABLE).
This review included 2 RCTs that compared DPNB with EMLA in 133 newborns. Infants who received DPNB had significantly lower heart rates (–17 bpm; 95% confidence interval [CI], –23 to –11).1 The review concluded that DPNB is the most effective method of anesthesia during circumcision. Comparison of effect sizes between studies may be inaccurate because of different study conditions, however.
TABLE
Comparative outcomes for circumcision anesthesia
| Type of anesthesia | Decrease in heart rate (bpm) vs placebo1 | Decrease in crying time (%) vs placebo1 | Mean proportion of time crying during foreskin separation (SD)2 | Mean proportion of time crying during clamping (SD)2 | Mean heart rate change (bpm) from baseline during separation (SD)2 |
|---|---|---|---|---|---|
| DPNB | –35 (95% CI, –41 to –30) N=592 | –54% (95% CI, –64 to –44) N=592 | 0.65 (0.33) N=14 | 0.41 (0.35) N=14 | 30.9 (32.6) N=14 |
| RB | –29 (95% CI, –52 to –7) N=12 | –26.3% (95% CI, –38 to –15) N=65 | 0.54 (0.38) N=12 | 0.37 (0.24) N=12 | 20.2 (32.1) N=12 |
| EMLA | –15 (95% CI, –19 to –10) N=200 | –15.2% (95% CI, –21 to –9.3) N=200 | 0.82 (0.17) N=15 | 0.55 (0.32) N=15 | 41.4 (31.4) N=15 |
| Placebo | NA | NA | 0.98 (0.05) N=11 | 0.85 (0.21) N=11 | 53.0 (46.2) N=11 |
| bpm, beats per minute; CI, confidence interval; DPNB, dorsal penile nerve block; EMLA, eutectic mixture of local anesthetics; NA, not applicable; RB, ring block; SD, standard deviation. | |||||
Direct comparison ranks RB first, DPNB second, EMLA third
The only head-to-head comparison of DPNB, RB, EMLA, and placebo is an RCT of 52 neonates, which found that RB resulted in the shortest mean crying time during painful procedures and the lowest increase from baseline in mean heart rate during foreskin separation. DPNB was the next most effective anesthetic; EMLA, although superior to placebo, was the least effective.2
Mogen clamp shortens procedure (and pain) more than other clamps
Three small RCTs evaluated procedure time using different types of instruments for circumcision.3-5 Two RCTS, in 57 and 48 newborns, compared the Mogen clamp with the Gomco clamp. The procedure time for the Mogen clamp was 1.9 times shorter than for the Gomco clamp in the first study (7.2 ± 0.32 vs 13.9 ± 0.32 min; P=.0001) and 2.5 times shorter in the second study (1.35 ± 0.32 vs 3.48 ± 1 min), thereby decreasing duration of pain.3,4 One of the RCTs found a significantly smaller heart rate increase from baseline for the Mogen clamp (8%) than the Gomco clamp (24%).4
In an RCT of 59 newborns, procedure time was significantly shorter with the Mogen clamp (12 ± 0.9 min) vs the PlastiBell circumcision device (20 ± 1.7 min).5
Useful adjuncts: A pacifier and a comfy chair
Effective adjuncts to DPNB include NNS, a sucrose pacifier, and use of a padded chair.6,7 An RCT of 44 newborns given a DPNB found that adjunctive NNS reduced crying time to 4.2 ± 2.6 min compared with a control time of 6.3 ± 2.35 min.6
Another RCT of 80 infants, all given a DPNB, found significantly lower behavioral distress scores (on a 3-point scale, with 3 being a sustained cry) among infants using a sucrose pacifier (0.45; standard deviation [SD]=0.80; P=.002) and padded chair (0.49; SD=0.52; P=.007) compared with controls (1.12; SD=0.48; P<.001).7
Recommendations
The American Academy of Pediatrics recommends analgesia during circumcision because sufficient evidence exists that the procedure causes pain. EMLA cream, DPNB, and RB are all options; RB may provide the most effective analgesia. A sucrose pacifier and a padded chair may be effective adjuncts.8
1. Brady-Fryer B, Wiebe N, Lander JA. Pain relief for neonatal circumcision. Cochrane Database Syst Rev. 2004;(4):CD004217.-
2. Lander J, Brady-Fryer B, Metcalfe JB, et al. Comparison of ring block, dorsal penile nerve block, and topical anesthesia for neonatal circumcision: a randomized controlled trial. JAMA. 1997;278:2157-2162.
3. Kaufman GE, Cimo S, Miller LW, et al. An evaluation of the effects of sucrose on neonatal pain with 2 commonly used circumcision methods. Am J Obstet Gynecol. 2002;186:564-568.
4. Kurtis PS, DeSilva HN, Bernstein BA, et al. A comparison of the Mogen and Gomco clamps in combination with dorsal penile nerve block in minimizing the pain of neonatal circumcision. Pediatrics. 1999;103:E23.-
5. Taeusch HW, Martinez AM, Partridge JC, et al. Pain during Mogen or PlastiBell circumcision. J Perinatol. 2002;22:214-218.
6. South MM, Strauss RA, South AP, et al. The use of non-nutritive sucking to decrease the physiologic pain response during neonatal circumcision: a randomized controlled trial. Am J Obstet Gynecol. 2005;193:537-542.
7. Stang HJ, Snellman LW, Condon LM, et al. Beyond dorsal penile nerve block: a more humane circumcision. Pediatrics. 1997;100:E3.-
8. American Academy of Pediatrics Task Force on Circumcision. Circumcision policy statement. Pediatrics. 1999;103:686-693.
DORSAL PENILE NERVE BLOCK (DPNB), ring block (RB), and eutectic mixture of local anesthetics (EMLA) all control pain effectively during neonatal circumcision (strength of recommendation [SOR]: A, systematic review). An RB may provide superior pain relief to DPNB and EMLA (SOR: B, limited-quality evidence).
Using a Mogen clamp reduces pain by shortening procedure time (SOR: A, randomized controlled trials [RCTs]). Effective adjuncts to pain relief include nonnutritive sucking (NNS; a pacifier without sucrose), a sucrose pacifier, and use of a padded chair (SOR: A, RCTs).
Evidence summary
Outcome assessment of neonatal pain response includes heart rate, crying time, procedure length, and behavioral distress scores. A Cochrane systematic review of 35 RCTs with a total of 1997 newborns evaluated DPNB, RB, and EMLA for pain relief during circumcision.1 All 3 methods were more effective than placebo or no treatment. Studies of DPNB reported lowered heart rates and shorter crying times than studies with EMLA vs placebo and RB vs placebo (TABLE).
This review included 2 RCTs that compared DPNB with EMLA in 133 newborns. Infants who received DPNB had significantly lower heart rates (–17 bpm; 95% confidence interval [CI], –23 to –11).1 The review concluded that DPNB is the most effective method of anesthesia during circumcision. Comparison of effect sizes between studies may be inaccurate because of different study conditions, however.
TABLE
Comparative outcomes for circumcision anesthesia
| Type of anesthesia | Decrease in heart rate (bpm) vs placebo1 | Decrease in crying time (%) vs placebo1 | Mean proportion of time crying during foreskin separation (SD)2 | Mean proportion of time crying during clamping (SD)2 | Mean heart rate change (bpm) from baseline during separation (SD)2 |
|---|---|---|---|---|---|
| DPNB | –35 (95% CI, –41 to –30) N=592 | –54% (95% CI, –64 to –44) N=592 | 0.65 (0.33) N=14 | 0.41 (0.35) N=14 | 30.9 (32.6) N=14 |
| RB | –29 (95% CI, –52 to –7) N=12 | –26.3% (95% CI, –38 to –15) N=65 | 0.54 (0.38) N=12 | 0.37 (0.24) N=12 | 20.2 (32.1) N=12 |
| EMLA | –15 (95% CI, –19 to –10) N=200 | –15.2% (95% CI, –21 to –9.3) N=200 | 0.82 (0.17) N=15 | 0.55 (0.32) N=15 | 41.4 (31.4) N=15 |
| Placebo | NA | NA | 0.98 (0.05) N=11 | 0.85 (0.21) N=11 | 53.0 (46.2) N=11 |
| bpm, beats per minute; CI, confidence interval; DPNB, dorsal penile nerve block; EMLA, eutectic mixture of local anesthetics; NA, not applicable; RB, ring block; SD, standard deviation. | |||||
Direct comparison ranks RB first, DPNB second, EMLA third
The only head-to-head comparison of DPNB, RB, EMLA, and placebo is an RCT of 52 neonates, which found that RB resulted in the shortest mean crying time during painful procedures and the lowest increase from baseline in mean heart rate during foreskin separation. DPNB was the next most effective anesthetic; EMLA, although superior to placebo, was the least effective.2
Mogen clamp shortens procedure (and pain) more than other clamps
Three small RCTs evaluated procedure time using different types of instruments for circumcision.3-5 Two RCTS, in 57 and 48 newborns, compared the Mogen clamp with the Gomco clamp. The procedure time for the Mogen clamp was 1.9 times shorter than for the Gomco clamp in the first study (7.2 ± 0.32 vs 13.9 ± 0.32 min; P=.0001) and 2.5 times shorter in the second study (1.35 ± 0.32 vs 3.48 ± 1 min), thereby decreasing duration of pain.3,4 One of the RCTs found a significantly smaller heart rate increase from baseline for the Mogen clamp (8%) than the Gomco clamp (24%).4
In an RCT of 59 newborns, procedure time was significantly shorter with the Mogen clamp (12 ± 0.9 min) vs the PlastiBell circumcision device (20 ± 1.7 min).5
Useful adjuncts: A pacifier and a comfy chair
Effective adjuncts to DPNB include NNS, a sucrose pacifier, and use of a padded chair.6,7 An RCT of 44 newborns given a DPNB found that adjunctive NNS reduced crying time to 4.2 ± 2.6 min compared with a control time of 6.3 ± 2.35 min.6
Another RCT of 80 infants, all given a DPNB, found significantly lower behavioral distress scores (on a 3-point scale, with 3 being a sustained cry) among infants using a sucrose pacifier (0.45; standard deviation [SD]=0.80; P=.002) and padded chair (0.49; SD=0.52; P=.007) compared with controls (1.12; SD=0.48; P<.001).7
Recommendations
The American Academy of Pediatrics recommends analgesia during circumcision because sufficient evidence exists that the procedure causes pain. EMLA cream, DPNB, and RB are all options; RB may provide the most effective analgesia. A sucrose pacifier and a padded chair may be effective adjuncts.8
DORSAL PENILE NERVE BLOCK (DPNB), ring block (RB), and eutectic mixture of local anesthetics (EMLA) all control pain effectively during neonatal circumcision (strength of recommendation [SOR]: A, systematic review). An RB may provide superior pain relief to DPNB and EMLA (SOR: B, limited-quality evidence).
Using a Mogen clamp reduces pain by shortening procedure time (SOR: A, randomized controlled trials [RCTs]). Effective adjuncts to pain relief include nonnutritive sucking (NNS; a pacifier without sucrose), a sucrose pacifier, and use of a padded chair (SOR: A, RCTs).
Evidence summary
Outcome assessment of neonatal pain response includes heart rate, crying time, procedure length, and behavioral distress scores. A Cochrane systematic review of 35 RCTs with a total of 1997 newborns evaluated DPNB, RB, and EMLA for pain relief during circumcision.1 All 3 methods were more effective than placebo or no treatment. Studies of DPNB reported lowered heart rates and shorter crying times than studies with EMLA vs placebo and RB vs placebo (TABLE).
This review included 2 RCTs that compared DPNB with EMLA in 133 newborns. Infants who received DPNB had significantly lower heart rates (–17 bpm; 95% confidence interval [CI], –23 to –11).1 The review concluded that DPNB is the most effective method of anesthesia during circumcision. Comparison of effect sizes between studies may be inaccurate because of different study conditions, however.
TABLE
Comparative outcomes for circumcision anesthesia
| Type of anesthesia | Decrease in heart rate (bpm) vs placebo1 | Decrease in crying time (%) vs placebo1 | Mean proportion of time crying during foreskin separation (SD)2 | Mean proportion of time crying during clamping (SD)2 | Mean heart rate change (bpm) from baseline during separation (SD)2 |
|---|---|---|---|---|---|
| DPNB | –35 (95% CI, –41 to –30) N=592 | –54% (95% CI, –64 to –44) N=592 | 0.65 (0.33) N=14 | 0.41 (0.35) N=14 | 30.9 (32.6) N=14 |
| RB | –29 (95% CI, –52 to –7) N=12 | –26.3% (95% CI, –38 to –15) N=65 | 0.54 (0.38) N=12 | 0.37 (0.24) N=12 | 20.2 (32.1) N=12 |
| EMLA | –15 (95% CI, –19 to –10) N=200 | –15.2% (95% CI, –21 to –9.3) N=200 | 0.82 (0.17) N=15 | 0.55 (0.32) N=15 | 41.4 (31.4) N=15 |
| Placebo | NA | NA | 0.98 (0.05) N=11 | 0.85 (0.21) N=11 | 53.0 (46.2) N=11 |
| bpm, beats per minute; CI, confidence interval; DPNB, dorsal penile nerve block; EMLA, eutectic mixture of local anesthetics; NA, not applicable; RB, ring block; SD, standard deviation. | |||||
Direct comparison ranks RB first, DPNB second, EMLA third
The only head-to-head comparison of DPNB, RB, EMLA, and placebo is an RCT of 52 neonates, which found that RB resulted in the shortest mean crying time during painful procedures and the lowest increase from baseline in mean heart rate during foreskin separation. DPNB was the next most effective anesthetic; EMLA, although superior to placebo, was the least effective.2
Mogen clamp shortens procedure (and pain) more than other clamps
Three small RCTs evaluated procedure time using different types of instruments for circumcision.3-5 Two RCTS, in 57 and 48 newborns, compared the Mogen clamp with the Gomco clamp. The procedure time for the Mogen clamp was 1.9 times shorter than for the Gomco clamp in the first study (7.2 ± 0.32 vs 13.9 ± 0.32 min; P=.0001) and 2.5 times shorter in the second study (1.35 ± 0.32 vs 3.48 ± 1 min), thereby decreasing duration of pain.3,4 One of the RCTs found a significantly smaller heart rate increase from baseline for the Mogen clamp (8%) than the Gomco clamp (24%).4
In an RCT of 59 newborns, procedure time was significantly shorter with the Mogen clamp (12 ± 0.9 min) vs the PlastiBell circumcision device (20 ± 1.7 min).5
Useful adjuncts: A pacifier and a comfy chair
Effective adjuncts to DPNB include NNS, a sucrose pacifier, and use of a padded chair.6,7 An RCT of 44 newborns given a DPNB found that adjunctive NNS reduced crying time to 4.2 ± 2.6 min compared with a control time of 6.3 ± 2.35 min.6
Another RCT of 80 infants, all given a DPNB, found significantly lower behavioral distress scores (on a 3-point scale, with 3 being a sustained cry) among infants using a sucrose pacifier (0.45; standard deviation [SD]=0.80; P=.002) and padded chair (0.49; SD=0.52; P=.007) compared with controls (1.12; SD=0.48; P<.001).7
Recommendations
The American Academy of Pediatrics recommends analgesia during circumcision because sufficient evidence exists that the procedure causes pain. EMLA cream, DPNB, and RB are all options; RB may provide the most effective analgesia. A sucrose pacifier and a padded chair may be effective adjuncts.8
1. Brady-Fryer B, Wiebe N, Lander JA. Pain relief for neonatal circumcision. Cochrane Database Syst Rev. 2004;(4):CD004217.-
2. Lander J, Brady-Fryer B, Metcalfe JB, et al. Comparison of ring block, dorsal penile nerve block, and topical anesthesia for neonatal circumcision: a randomized controlled trial. JAMA. 1997;278:2157-2162.
3. Kaufman GE, Cimo S, Miller LW, et al. An evaluation of the effects of sucrose on neonatal pain with 2 commonly used circumcision methods. Am J Obstet Gynecol. 2002;186:564-568.
4. Kurtis PS, DeSilva HN, Bernstein BA, et al. A comparison of the Mogen and Gomco clamps in combination with dorsal penile nerve block in minimizing the pain of neonatal circumcision. Pediatrics. 1999;103:E23.-
5. Taeusch HW, Martinez AM, Partridge JC, et al. Pain during Mogen or PlastiBell circumcision. J Perinatol. 2002;22:214-218.
6. South MM, Strauss RA, South AP, et al. The use of non-nutritive sucking to decrease the physiologic pain response during neonatal circumcision: a randomized controlled trial. Am J Obstet Gynecol. 2005;193:537-542.
7. Stang HJ, Snellman LW, Condon LM, et al. Beyond dorsal penile nerve block: a more humane circumcision. Pediatrics. 1997;100:E3.-
8. American Academy of Pediatrics Task Force on Circumcision. Circumcision policy statement. Pediatrics. 1999;103:686-693.
1. Brady-Fryer B, Wiebe N, Lander JA. Pain relief for neonatal circumcision. Cochrane Database Syst Rev. 2004;(4):CD004217.-
2. Lander J, Brady-Fryer B, Metcalfe JB, et al. Comparison of ring block, dorsal penile nerve block, and topical anesthesia for neonatal circumcision: a randomized controlled trial. JAMA. 1997;278:2157-2162.
3. Kaufman GE, Cimo S, Miller LW, et al. An evaluation of the effects of sucrose on neonatal pain with 2 commonly used circumcision methods. Am J Obstet Gynecol. 2002;186:564-568.
4. Kurtis PS, DeSilva HN, Bernstein BA, et al. A comparison of the Mogen and Gomco clamps in combination with dorsal penile nerve block in minimizing the pain of neonatal circumcision. Pediatrics. 1999;103:E23.-
5. Taeusch HW, Martinez AM, Partridge JC, et al. Pain during Mogen or PlastiBell circumcision. J Perinatol. 2002;22:214-218.
6. South MM, Strauss RA, South AP, et al. The use of non-nutritive sucking to decrease the physiologic pain response during neonatal circumcision: a randomized controlled trial. Am J Obstet Gynecol. 2005;193:537-542.
7. Stang HJ, Snellman LW, Condon LM, et al. Beyond dorsal penile nerve block: a more humane circumcision. Pediatrics. 1997;100:E3.-
8. American Academy of Pediatrics Task Force on Circumcision. Circumcision policy statement. Pediatrics. 1999;103:686-693.
Evidence-based answers from the Family Physicians Inquiries Network
What are the best prophylactic drugs for migraine?
BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine (strength of recommendation: A, multiple, well-designed, randomized controlled trials [RCTs]).
Evidence summary
Many medications have been evaluated for migraine prophylaxis. However, very few head-to-head trials of more than 2 drugs have been published, and no recent meta-analyses of available drug classes have been performed. The most commonly evaluated outcome is a 50% reduction in headache frequency.
Propranolol and timolol offer consistent prevention
Propranolol and timolol have consistently demonstrated efficacy for preventing episodic migraine. In a 1991 meta-analysis, propranolol resulted in a 44% reduction in the headache index—a composite score that takes into account both intensity and duration—compared with a 14% reduction for placebo.1
Less evidence supports other beta-blockers
Atenolol, metoprolol, and nadolol have demonstrated a moderate effect, but less evidence exists to support their use.2 A recent trial comparing metoprolol and nebivolol demonstrated a positive response—defined as a 50% reduction in headache frequency—to each drug at 14 weeks (57% of metoprolol-treated and 50% of nebivolol-treated patients), but noted that nebivolol was better tolerated.3
Beta-blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) appear to be ineffective for migraine prevention.4
Amitriptyline works better than propranolol for some migraines
Amitriptyline is the most often studied antidepressant and the only one with consistent support for efficacy in preventing migraine. A 1981 trial found amitriptyline to be more effective than propranolol in mixed migraine-tension-type headache, whereas propranolol was more effective for migraine alone.5
Some support for fluoxetine, none for similar drugs
Limited evidence exists for the use of fluoxetine, 20 mg daily. A small 1999 study of patients with migraine without aura found a 57% reduction in total pain index—a value based on pain intensity and hours of headache per month—with fluoxetine compared with an insignificant 31% reduction with placebo.6
No evidence from controlled trials supports the use of fluvoxamine, paroxetine, sertraline, phenelzine, venlafaxine, mirtazapine, trazodone, or bupropion.4
Divalproex sodium, sodium valproate are effective
Divalproex sodium and sodium valproate show strong, consistent evidence of efficacy; they may be particularly useful for patients with prolonged or atypical migraine aura.4 Initial studies of delayed-release divalproex at doses ranging from 500 to 1500 mg daily found that 44% of divalproex-treated patients reported a 50% reduction in migraine frequency, compared with 21% in the placebo group (number needed to treat [NNT]=4).7
A more recent study of the extended-release form of divalproex sodium demonstrated a 4-week reduction in headache rate to 1.2 from a baseline of 4.4, compared with a decrease of 0.6 for placebo (95% confidence interval [CI] of treatment difference, 0.2-1.2).8
TABLE
Recommended drugs for migraine prophylaxis13
| Drug | Dose | Comments |
|---|---|---|
| Propranolol | 80-240 mg/d | May cause fatigue. When used in combination with rizatriptan, give a lower dose of rizatriptan. |
| Timolol | 20-30 mg/d | As with propranolol, may cause fatigue. Avoid β-blockers in patients with asthma or Raynaud’s disease. |
| Amitriptyline | 25-150 mg/d | Drowsiness, weight gain, and significant anticholinergic adverse events are common. |
| Divalproex sodium; Sodium valproate | 500-1500 mg/d; 800-1500 mg/d | Side effects include nausea, drowsiness, weight gain, hair loss, and tremor. Hepatotoxicity, pancreatitis, and hyperammonemia have been reported rarely. Pregnancy category D. |
| Topiramate | 100-200 mg/d | Paresthesia is the most common adverse event; fatigue, nausea, anorexia, and cognitive symptoms are less common. Carbonic anhydrase inhibition may cause metabolic acidosis. Acute myopia and angle closure glaucoma are rare events. |
Topiramate may decrease frequency as much as propranolol
Topiramate has significantly reduced the mean frequency of episodic migraine at doses of 100 to 200 mg daily and also improved secondary end points, including number of migraine days per month, use of acute medication, and daily activity.9 One study found that topiramate 100 mg daily had comparable efficacy to propranolol 160 mg daily; both drugs decreased monthly migraine frequency to 1.6 from a baseline of 4.9 with topiramate and 5.1 with propranolol (95% CI for the pair-wise difference of topiramate minus propranolol,-0.58 to 0.60).10
Anticonvulsants also reduce migraine frequency
A 2004 Cochrane review of anticonvulsant drugs for migraine prophylaxis found that anticonvulsants, as a class, reduce migraine frequency by about 1.3 attacks per 28 days when compared with placebo (based on 10 trials [N=902]). When analyzing data on relative frequency of migraines, data from 13 trials (N=1773) were combined and showed that anticonvulsants more than doubled the number of patients with a 50% or greater decrease in migraine frequency relative to placebo (relative risk=2.25; 95% CI, 1.79-2.84; NNT=3.9; 95% CI, 3.4-4.7).11
Other drugs to keep on your radar
Agents available in the United States that have at least limited evidence supporting their use to prevent episodic migraine include gabapentin, lisinopril, candesartan, memantine, riboflavin, magnesium, feverfew, coenzyme Q10, butterbur, and melatonin.
Drugs so far proved ineffective in preventing episodic migraine include clonidine, carbamazepine, clonazepam, vigabatrin, oxcarbazepine, zonisamide, lamotrigine, nifedipine, and acetazolamide. Botulinum toxin type A given by intramuscular injection in the head and neck region has demonstrated limited efficacy in chronic headache disorders, but doesn’t prevent episodic migraine.12
Recommendations
The 2000 guidelines of the American Association of Neurology address Group 1 (first-line) drugs and Group 2 drugs:
Group 1 drugs (medium to high efficacy, good strength of evidence, and a range of severity [mild to moderate] and frequency [infrequent to frequent] of side effects) include amitriptyline, divalproex sodium, propranolol, and timolol.
Group 2 drugs (lower efficacy than Group 1, or limited strength of evidence, and mild to moderate side effects) include aspirin (but not combination products), atenolol, fenoprofen, feverfew, flurbiprofen, fluoxetine, gabapentin, guanfacine, ketoprofen, magnesium, mefenamic acid, metoprolol, nadolol, naproxen, nimodipine, verapamil, and vitamin B2.13
Topiramate was still under study when the guidelines were released and wasn’t approved by the US Food and Drug Administration for migraine prophylaxis until 2004. The 2000 guidelines are undergoing revision.
1. Holroyd KA, Penzien DB, Cordingley GE. Propranolol in the management of recurrent migraine: a meta-analytic review. Headache. 1991;31:333-340.
2. Silberstein SD, Goadsby PJ. Migraine: preventive treatment. Cephalalgia. 2002;22:491-512.
3. Schellenberg R, Lichtenthal A, Wöhling H, et al. Nebivolol and metoprolol for treating migraine: an advance on β-blocker treatment? Headache. 2008;48:118-125.
4. Snow V, Weiss K, Wall EM, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137:840-849.
5. Mathew NT. Prophylaxis of migraine and mixed headache: a randomized controlled study. Headache. 1981;21:105-109.
6. d’Amato CC, Pizza V, Marmolo T, et al. Fluoxetine for migraine prophylaxis: a double-blind trial. Headache. 1999;39:716-719.
7. Klapper J. Divalproex sodium in migraine prophylaxis: a dose-controlled study [published correction appears in Cephalalgia. 1997;17:798]. Cephalalgia. 1997;17:103-108.
8. Freitag FG, Collins SD, Carlson HA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology. 2002;58:1652-1659.
9. Kaniecki R. Neuromodulators for migraine prevention. Headache. 2008;48:586-600.
10. Diener HC, Tfelt-Hansen P, Dahlof C, et al. Topiramate in migraine prophylaxis—results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004;251:943-950.
11. Chronicle EP, Mulleners WM. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev. 2004;(3):CD003226.
12. Blumenfeld AM, Schim JD, Chippendale TJ. Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache. 2008;48:210-220.
13. Ramadan NM, Silberstein SD, Freitag FG, et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. 2000. Available at: www.aan.com/professionals/practice/pdfs/gl0090.pdf. Accessed March 26, 2008.
BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine (strength of recommendation: A, multiple, well-designed, randomized controlled trials [RCTs]).
Evidence summary
Many medications have been evaluated for migraine prophylaxis. However, very few head-to-head trials of more than 2 drugs have been published, and no recent meta-analyses of available drug classes have been performed. The most commonly evaluated outcome is a 50% reduction in headache frequency.
Propranolol and timolol offer consistent prevention
Propranolol and timolol have consistently demonstrated efficacy for preventing episodic migraine. In a 1991 meta-analysis, propranolol resulted in a 44% reduction in the headache index—a composite score that takes into account both intensity and duration—compared with a 14% reduction for placebo.1
Less evidence supports other beta-blockers
Atenolol, metoprolol, and nadolol have demonstrated a moderate effect, but less evidence exists to support their use.2 A recent trial comparing metoprolol and nebivolol demonstrated a positive response—defined as a 50% reduction in headache frequency—to each drug at 14 weeks (57% of metoprolol-treated and 50% of nebivolol-treated patients), but noted that nebivolol was better tolerated.3
Beta-blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) appear to be ineffective for migraine prevention.4
Amitriptyline works better than propranolol for some migraines
Amitriptyline is the most often studied antidepressant and the only one with consistent support for efficacy in preventing migraine. A 1981 trial found amitriptyline to be more effective than propranolol in mixed migraine-tension-type headache, whereas propranolol was more effective for migraine alone.5
Some support for fluoxetine, none for similar drugs
Limited evidence exists for the use of fluoxetine, 20 mg daily. A small 1999 study of patients with migraine without aura found a 57% reduction in total pain index—a value based on pain intensity and hours of headache per month—with fluoxetine compared with an insignificant 31% reduction with placebo.6
No evidence from controlled trials supports the use of fluvoxamine, paroxetine, sertraline, phenelzine, venlafaxine, mirtazapine, trazodone, or bupropion.4
Divalproex sodium, sodium valproate are effective
Divalproex sodium and sodium valproate show strong, consistent evidence of efficacy; they may be particularly useful for patients with prolonged or atypical migraine aura.4 Initial studies of delayed-release divalproex at doses ranging from 500 to 1500 mg daily found that 44% of divalproex-treated patients reported a 50% reduction in migraine frequency, compared with 21% in the placebo group (number needed to treat [NNT]=4).7
A more recent study of the extended-release form of divalproex sodium demonstrated a 4-week reduction in headache rate to 1.2 from a baseline of 4.4, compared with a decrease of 0.6 for placebo (95% confidence interval [CI] of treatment difference, 0.2-1.2).8
TABLE
Recommended drugs for migraine prophylaxis13
| Drug | Dose | Comments |
|---|---|---|
| Propranolol | 80-240 mg/d | May cause fatigue. When used in combination with rizatriptan, give a lower dose of rizatriptan. |
| Timolol | 20-30 mg/d | As with propranolol, may cause fatigue. Avoid β-blockers in patients with asthma or Raynaud’s disease. |
| Amitriptyline | 25-150 mg/d | Drowsiness, weight gain, and significant anticholinergic adverse events are common. |
| Divalproex sodium; Sodium valproate | 500-1500 mg/d; 800-1500 mg/d | Side effects include nausea, drowsiness, weight gain, hair loss, and tremor. Hepatotoxicity, pancreatitis, and hyperammonemia have been reported rarely. Pregnancy category D. |
| Topiramate | 100-200 mg/d | Paresthesia is the most common adverse event; fatigue, nausea, anorexia, and cognitive symptoms are less common. Carbonic anhydrase inhibition may cause metabolic acidosis. Acute myopia and angle closure glaucoma are rare events. |
Topiramate may decrease frequency as much as propranolol
Topiramate has significantly reduced the mean frequency of episodic migraine at doses of 100 to 200 mg daily and also improved secondary end points, including number of migraine days per month, use of acute medication, and daily activity.9 One study found that topiramate 100 mg daily had comparable efficacy to propranolol 160 mg daily; both drugs decreased monthly migraine frequency to 1.6 from a baseline of 4.9 with topiramate and 5.1 with propranolol (95% CI for the pair-wise difference of topiramate minus propranolol,-0.58 to 0.60).10
Anticonvulsants also reduce migraine frequency
A 2004 Cochrane review of anticonvulsant drugs for migraine prophylaxis found that anticonvulsants, as a class, reduce migraine frequency by about 1.3 attacks per 28 days when compared with placebo (based on 10 trials [N=902]). When analyzing data on relative frequency of migraines, data from 13 trials (N=1773) were combined and showed that anticonvulsants more than doubled the number of patients with a 50% or greater decrease in migraine frequency relative to placebo (relative risk=2.25; 95% CI, 1.79-2.84; NNT=3.9; 95% CI, 3.4-4.7).11
Other drugs to keep on your radar
Agents available in the United States that have at least limited evidence supporting their use to prevent episodic migraine include gabapentin, lisinopril, candesartan, memantine, riboflavin, magnesium, feverfew, coenzyme Q10, butterbur, and melatonin.
Drugs so far proved ineffective in preventing episodic migraine include clonidine, carbamazepine, clonazepam, vigabatrin, oxcarbazepine, zonisamide, lamotrigine, nifedipine, and acetazolamide. Botulinum toxin type A given by intramuscular injection in the head and neck region has demonstrated limited efficacy in chronic headache disorders, but doesn’t prevent episodic migraine.12
Recommendations
The 2000 guidelines of the American Association of Neurology address Group 1 (first-line) drugs and Group 2 drugs:
Group 1 drugs (medium to high efficacy, good strength of evidence, and a range of severity [mild to moderate] and frequency [infrequent to frequent] of side effects) include amitriptyline, divalproex sodium, propranolol, and timolol.
Group 2 drugs (lower efficacy than Group 1, or limited strength of evidence, and mild to moderate side effects) include aspirin (but not combination products), atenolol, fenoprofen, feverfew, flurbiprofen, fluoxetine, gabapentin, guanfacine, ketoprofen, magnesium, mefenamic acid, metoprolol, nadolol, naproxen, nimodipine, verapamil, and vitamin B2.13
Topiramate was still under study when the guidelines were released and wasn’t approved by the US Food and Drug Administration for migraine prophylaxis until 2004. The 2000 guidelines are undergoing revision.
BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine (strength of recommendation: A, multiple, well-designed, randomized controlled trials [RCTs]).
Evidence summary
Many medications have been evaluated for migraine prophylaxis. However, very few head-to-head trials of more than 2 drugs have been published, and no recent meta-analyses of available drug classes have been performed. The most commonly evaluated outcome is a 50% reduction in headache frequency.
Propranolol and timolol offer consistent prevention
Propranolol and timolol have consistently demonstrated efficacy for preventing episodic migraine. In a 1991 meta-analysis, propranolol resulted in a 44% reduction in the headache index—a composite score that takes into account both intensity and duration—compared with a 14% reduction for placebo.1
Less evidence supports other beta-blockers
Atenolol, metoprolol, and nadolol have demonstrated a moderate effect, but less evidence exists to support their use.2 A recent trial comparing metoprolol and nebivolol demonstrated a positive response—defined as a 50% reduction in headache frequency—to each drug at 14 weeks (57% of metoprolol-treated and 50% of nebivolol-treated patients), but noted that nebivolol was better tolerated.3
Beta-blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) appear to be ineffective for migraine prevention.4
Amitriptyline works better than propranolol for some migraines
Amitriptyline is the most often studied antidepressant and the only one with consistent support for efficacy in preventing migraine. A 1981 trial found amitriptyline to be more effective than propranolol in mixed migraine-tension-type headache, whereas propranolol was more effective for migraine alone.5
Some support for fluoxetine, none for similar drugs
Limited evidence exists for the use of fluoxetine, 20 mg daily. A small 1999 study of patients with migraine without aura found a 57% reduction in total pain index—a value based on pain intensity and hours of headache per month—with fluoxetine compared with an insignificant 31% reduction with placebo.6
No evidence from controlled trials supports the use of fluvoxamine, paroxetine, sertraline, phenelzine, venlafaxine, mirtazapine, trazodone, or bupropion.4
Divalproex sodium, sodium valproate are effective
Divalproex sodium and sodium valproate show strong, consistent evidence of efficacy; they may be particularly useful for patients with prolonged or atypical migraine aura.4 Initial studies of delayed-release divalproex at doses ranging from 500 to 1500 mg daily found that 44% of divalproex-treated patients reported a 50% reduction in migraine frequency, compared with 21% in the placebo group (number needed to treat [NNT]=4).7
A more recent study of the extended-release form of divalproex sodium demonstrated a 4-week reduction in headache rate to 1.2 from a baseline of 4.4, compared with a decrease of 0.6 for placebo (95% confidence interval [CI] of treatment difference, 0.2-1.2).8
TABLE
Recommended drugs for migraine prophylaxis13
| Drug | Dose | Comments |
|---|---|---|
| Propranolol | 80-240 mg/d | May cause fatigue. When used in combination with rizatriptan, give a lower dose of rizatriptan. |
| Timolol | 20-30 mg/d | As with propranolol, may cause fatigue. Avoid β-blockers in patients with asthma or Raynaud’s disease. |
| Amitriptyline | 25-150 mg/d | Drowsiness, weight gain, and significant anticholinergic adverse events are common. |
| Divalproex sodium; Sodium valproate | 500-1500 mg/d; 800-1500 mg/d | Side effects include nausea, drowsiness, weight gain, hair loss, and tremor. Hepatotoxicity, pancreatitis, and hyperammonemia have been reported rarely. Pregnancy category D. |
| Topiramate | 100-200 mg/d | Paresthesia is the most common adverse event; fatigue, nausea, anorexia, and cognitive symptoms are less common. Carbonic anhydrase inhibition may cause metabolic acidosis. Acute myopia and angle closure glaucoma are rare events. |
Topiramate may decrease frequency as much as propranolol
Topiramate has significantly reduced the mean frequency of episodic migraine at doses of 100 to 200 mg daily and also improved secondary end points, including number of migraine days per month, use of acute medication, and daily activity.9 One study found that topiramate 100 mg daily had comparable efficacy to propranolol 160 mg daily; both drugs decreased monthly migraine frequency to 1.6 from a baseline of 4.9 with topiramate and 5.1 with propranolol (95% CI for the pair-wise difference of topiramate minus propranolol,-0.58 to 0.60).10
Anticonvulsants also reduce migraine frequency
A 2004 Cochrane review of anticonvulsant drugs for migraine prophylaxis found that anticonvulsants, as a class, reduce migraine frequency by about 1.3 attacks per 28 days when compared with placebo (based on 10 trials [N=902]). When analyzing data on relative frequency of migraines, data from 13 trials (N=1773) were combined and showed that anticonvulsants more than doubled the number of patients with a 50% or greater decrease in migraine frequency relative to placebo (relative risk=2.25; 95% CI, 1.79-2.84; NNT=3.9; 95% CI, 3.4-4.7).11
Other drugs to keep on your radar
Agents available in the United States that have at least limited evidence supporting their use to prevent episodic migraine include gabapentin, lisinopril, candesartan, memantine, riboflavin, magnesium, feverfew, coenzyme Q10, butterbur, and melatonin.
Drugs so far proved ineffective in preventing episodic migraine include clonidine, carbamazepine, clonazepam, vigabatrin, oxcarbazepine, zonisamide, lamotrigine, nifedipine, and acetazolamide. Botulinum toxin type A given by intramuscular injection in the head and neck region has demonstrated limited efficacy in chronic headache disorders, but doesn’t prevent episodic migraine.12
Recommendations
The 2000 guidelines of the American Association of Neurology address Group 1 (first-line) drugs and Group 2 drugs:
Group 1 drugs (medium to high efficacy, good strength of evidence, and a range of severity [mild to moderate] and frequency [infrequent to frequent] of side effects) include amitriptyline, divalproex sodium, propranolol, and timolol.
Group 2 drugs (lower efficacy than Group 1, or limited strength of evidence, and mild to moderate side effects) include aspirin (but not combination products), atenolol, fenoprofen, feverfew, flurbiprofen, fluoxetine, gabapentin, guanfacine, ketoprofen, magnesium, mefenamic acid, metoprolol, nadolol, naproxen, nimodipine, verapamil, and vitamin B2.13
Topiramate was still under study when the guidelines were released and wasn’t approved by the US Food and Drug Administration for migraine prophylaxis until 2004. The 2000 guidelines are undergoing revision.
1. Holroyd KA, Penzien DB, Cordingley GE. Propranolol in the management of recurrent migraine: a meta-analytic review. Headache. 1991;31:333-340.
2. Silberstein SD, Goadsby PJ. Migraine: preventive treatment. Cephalalgia. 2002;22:491-512.
3. Schellenberg R, Lichtenthal A, Wöhling H, et al. Nebivolol and metoprolol for treating migraine: an advance on β-blocker treatment? Headache. 2008;48:118-125.
4. Snow V, Weiss K, Wall EM, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137:840-849.
5. Mathew NT. Prophylaxis of migraine and mixed headache: a randomized controlled study. Headache. 1981;21:105-109.
6. d’Amato CC, Pizza V, Marmolo T, et al. Fluoxetine for migraine prophylaxis: a double-blind trial. Headache. 1999;39:716-719.
7. Klapper J. Divalproex sodium in migraine prophylaxis: a dose-controlled study [published correction appears in Cephalalgia. 1997;17:798]. Cephalalgia. 1997;17:103-108.
8. Freitag FG, Collins SD, Carlson HA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology. 2002;58:1652-1659.
9. Kaniecki R. Neuromodulators for migraine prevention. Headache. 2008;48:586-600.
10. Diener HC, Tfelt-Hansen P, Dahlof C, et al. Topiramate in migraine prophylaxis—results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004;251:943-950.
11. Chronicle EP, Mulleners WM. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev. 2004;(3):CD003226.
12. Blumenfeld AM, Schim JD, Chippendale TJ. Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache. 2008;48:210-220.
13. Ramadan NM, Silberstein SD, Freitag FG, et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. 2000. Available at: www.aan.com/professionals/practice/pdfs/gl0090.pdf. Accessed March 26, 2008.
1. Holroyd KA, Penzien DB, Cordingley GE. Propranolol in the management of recurrent migraine: a meta-analytic review. Headache. 1991;31:333-340.
2. Silberstein SD, Goadsby PJ. Migraine: preventive treatment. Cephalalgia. 2002;22:491-512.
3. Schellenberg R, Lichtenthal A, Wöhling H, et al. Nebivolol and metoprolol for treating migraine: an advance on β-blocker treatment? Headache. 2008;48:118-125.
4. Snow V, Weiss K, Wall EM, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137:840-849.
5. Mathew NT. Prophylaxis of migraine and mixed headache: a randomized controlled study. Headache. 1981;21:105-109.
6. d’Amato CC, Pizza V, Marmolo T, et al. Fluoxetine for migraine prophylaxis: a double-blind trial. Headache. 1999;39:716-719.
7. Klapper J. Divalproex sodium in migraine prophylaxis: a dose-controlled study [published correction appears in Cephalalgia. 1997;17:798]. Cephalalgia. 1997;17:103-108.
8. Freitag FG, Collins SD, Carlson HA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology. 2002;58:1652-1659.
9. Kaniecki R. Neuromodulators for migraine prevention. Headache. 2008;48:586-600.
10. Diener HC, Tfelt-Hansen P, Dahlof C, et al. Topiramate in migraine prophylaxis—results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004;251:943-950.
11. Chronicle EP, Mulleners WM. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev. 2004;(3):CD003226.
12. Blumenfeld AM, Schim JD, Chippendale TJ. Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache. 2008;48:210-220.
13. Ramadan NM, Silberstein SD, Freitag FG, et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. 2000. Available at: www.aan.com/professionals/practice/pdfs/gl0090.pdf. Accessed March 26, 2008.
Evidence-based answers from the Family Physicians Inquiries Network
What are the most practical primary care screens for post-traumatic stress disorder?
The 4-item Primary Care Post-Traumatic Stress Disorder screen (PC-PTSD) is a simple and effective tool to identify symptoms of post-traumatic stress disorder (PTSD) in primary care patients (strength of recommendation [SOR]: B, 1 good-quality prospective cohort study and 1 good-quality retrospective cohort study). The 7-item Breslau screen also predictably identifies patients with PTSD symptoms (SOR: B, 1 good-quality prospective cohort study).
Evidence summary
About 8% of the US population will develop symptoms of PTSD at some point in their lives—usually as the result of a traumatic event, such as combat, a natural disaster, accident, or physical or sexual assault.1 Primary care settings tend to be the principal point of contact for patients with PTSD, although such patients rarely identify themselves as suffering from the disorder.2,3
Detailed diagnostic interviews and assessments are generally impractical in primary care.4 Brief, easy-to-complete screening tools can help clinicians identify patients with primary symptoms of PTSD.4
4-item screen assesses key characteristics of PTSD
The PC-PTSD (TABLE) is a 4-item screen that assesses the underlying characteristics specific to PTSD: re-experiencing, numbing, avoidance, and hyperarousal.4 It’s designed to be understandable to patients with an eighth-grade reading level and has been validated in a Department of Veterans Affairs (VA) primary care population (N=188).4
With a cutoff score of 3, the PCPTSD has a sensitivity of 78% and specificity of 87%, compared with the gold-standard Clinician-Administered PTSD Scale (CAPS).4 Positive responses warrant further evaluation of trauma symptoms and completion of the CAPS by a mental health provider to determine whether the patient may have PTSD or other trauma-related problems.5-7
TABLE
The primary care PTSD screen (PC-PTSD)4
| In your life, have you ever had any experience that was so frightening, horrible, or upsetting that, in the past month, you… |
| 1. Have had nightmares about it or thought about it when you did not want to? YES NO |
| 2. Tried hard not to think about it or went out of your way to avoid situations that reminded you of it? YES NO |
| 3. Were constantly on guard, watchful, or easily startled? YES NO |
| 4. Felt numb or detached from others, activities, or your surroundings? YES NO |
Breslau’s short screen addresses 7 specific symptoms
Breslau’s 7-item screening scale (available at http://ajp.psychiatryonline.org/cgi/content/full/156/6/908#T2) is another empirically tested, brief, simple means of identifying PTSD symptoms in primary care patients.2 (See also: www.pubmedcentral.nih.gov/articlerender.fcgifiartid=1484617.) Each item addresses a specific symptom.
The screen has been validated in a VA primary care clinic (N=134). With a cutoff score of 4, it has a sensitivity of 85% and specificity of 84%, yielding a positive predictive value of 71% and negative predictive value of 98%.2 The likelihood of a score <3 is 0.04 and a score >5 is 13.5. Scores of 3 to 5 have an indeterminate likelihood value (1.8). Patients with a positive screen should undergo further evaluation by a mental health provider.2
Leave lengthy screens to mental health professionals
The CAPS and the civilian version of the PTSD Symptom Checklist (PCL-C), both with 17 items, are widely used as “screens” for PTSD.7 However, their length and the recommendation that they be administered by a mental health professional make them cumbersome and impractical for use in primary care.7
Recommendations
A 2007 point-of-care guide written for primary care clinicians recommends Breslau’s short screening scale and the PCPTSD screen for use in this setting.1 Both the National Center for PTSD and Department of Defense Clinical Guidelines on PTSD recommend initial and annual screening using the PC-PTSD, PTSD Brief Screen, or Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) PTSD.8
Acknowledgements
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the United States Air Force Medical Service or the United States Air Force at large.
1. Ebell MH. Screening instruments for post-traumatic stress disorder. Am Fam Physician. 2007;76:1848-1849.
2. Kimerling R, Ouimette P, Prins A, et al. Brief report: utility of a short screening scale for DSM-IV PTSD in primary care. J Gen Intern Med. 2006;21:65-67.
3. Screen for PTSD symptoms. PTSD core annotation E. Available at: www.oqp.med.va.gov/cpg/PTSD/PTSD_cpg/content/core/annoC.htm. Accessed April 15, 2008.
4. Prins A, Ouimette P, Kimerling R, et al. The primary care PTSD screen (PC-PTSD): development and operating characteristics. Prim Care Psychiatry. 2003;9:9-14.
5. Ouimette P, Wade M, Prins A, et al. Identifying PTSD in primary care: comparison of the primary care-PTSD screen (PC-PTSD) and the general health questionnaire-12 (GHQ). J Anxiety Disord. 2008;22:337-343.
6. National Center for PTSD. Screening for PTSD in a primary care setting. Available at: www.ncptsd.va.gov/ncmain/ncdocs/fact_shts/fs_screen_disaster.html. Accessed April 15, 2008.
7. Griffin MG, Uhlmansiek MH, Resick PA, et al. Comparison of the posttraumatic stress disorder scale versus the clinician-administered posttraumatic stress disorder scale in domestic violence survivors. J Trauma Stress. 2004;17:497-503.
8. VA/DoD clinical practice guideline for the management of post-traumatic stress. Version 1.0; January 2004. Available at: www.guideline.gov/summary/summary.aspx?ss=15&doc_id=5187. Accessed April 15, 2008.
The 4-item Primary Care Post-Traumatic Stress Disorder screen (PC-PTSD) is a simple and effective tool to identify symptoms of post-traumatic stress disorder (PTSD) in primary care patients (strength of recommendation [SOR]: B, 1 good-quality prospective cohort study and 1 good-quality retrospective cohort study). The 7-item Breslau screen also predictably identifies patients with PTSD symptoms (SOR: B, 1 good-quality prospective cohort study).
Evidence summary
About 8% of the US population will develop symptoms of PTSD at some point in their lives—usually as the result of a traumatic event, such as combat, a natural disaster, accident, or physical or sexual assault.1 Primary care settings tend to be the principal point of contact for patients with PTSD, although such patients rarely identify themselves as suffering from the disorder.2,3
Detailed diagnostic interviews and assessments are generally impractical in primary care.4 Brief, easy-to-complete screening tools can help clinicians identify patients with primary symptoms of PTSD.4
4-item screen assesses key characteristics of PTSD
The PC-PTSD (TABLE) is a 4-item screen that assesses the underlying characteristics specific to PTSD: re-experiencing, numbing, avoidance, and hyperarousal.4 It’s designed to be understandable to patients with an eighth-grade reading level and has been validated in a Department of Veterans Affairs (VA) primary care population (N=188).4
With a cutoff score of 3, the PCPTSD has a sensitivity of 78% and specificity of 87%, compared with the gold-standard Clinician-Administered PTSD Scale (CAPS).4 Positive responses warrant further evaluation of trauma symptoms and completion of the CAPS by a mental health provider to determine whether the patient may have PTSD or other trauma-related problems.5-7
TABLE
The primary care PTSD screen (PC-PTSD)4
| In your life, have you ever had any experience that was so frightening, horrible, or upsetting that, in the past month, you… |
| 1. Have had nightmares about it or thought about it when you did not want to? YES NO |
| 2. Tried hard not to think about it or went out of your way to avoid situations that reminded you of it? YES NO |
| 3. Were constantly on guard, watchful, or easily startled? YES NO |
| 4. Felt numb or detached from others, activities, or your surroundings? YES NO |
Breslau’s short screen addresses 7 specific symptoms
Breslau’s 7-item screening scale (available at http://ajp.psychiatryonline.org/cgi/content/full/156/6/908#T2) is another empirically tested, brief, simple means of identifying PTSD symptoms in primary care patients.2 (See also: www.pubmedcentral.nih.gov/articlerender.fcgifiartid=1484617.) Each item addresses a specific symptom.
The screen has been validated in a VA primary care clinic (N=134). With a cutoff score of 4, it has a sensitivity of 85% and specificity of 84%, yielding a positive predictive value of 71% and negative predictive value of 98%.2 The likelihood of a score <3 is 0.04 and a score >5 is 13.5. Scores of 3 to 5 have an indeterminate likelihood value (1.8). Patients with a positive screen should undergo further evaluation by a mental health provider.2
Leave lengthy screens to mental health professionals
The CAPS and the civilian version of the PTSD Symptom Checklist (PCL-C), both with 17 items, are widely used as “screens” for PTSD.7 However, their length and the recommendation that they be administered by a mental health professional make them cumbersome and impractical for use in primary care.7
Recommendations
A 2007 point-of-care guide written for primary care clinicians recommends Breslau’s short screening scale and the PCPTSD screen for use in this setting.1 Both the National Center for PTSD and Department of Defense Clinical Guidelines on PTSD recommend initial and annual screening using the PC-PTSD, PTSD Brief Screen, or Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) PTSD.8
Acknowledgements
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the United States Air Force Medical Service or the United States Air Force at large.
The 4-item Primary Care Post-Traumatic Stress Disorder screen (PC-PTSD) is a simple and effective tool to identify symptoms of post-traumatic stress disorder (PTSD) in primary care patients (strength of recommendation [SOR]: B, 1 good-quality prospective cohort study and 1 good-quality retrospective cohort study). The 7-item Breslau screen also predictably identifies patients with PTSD symptoms (SOR: B, 1 good-quality prospective cohort study).
Evidence summary
About 8% of the US population will develop symptoms of PTSD at some point in their lives—usually as the result of a traumatic event, such as combat, a natural disaster, accident, or physical or sexual assault.1 Primary care settings tend to be the principal point of contact for patients with PTSD, although such patients rarely identify themselves as suffering from the disorder.2,3
Detailed diagnostic interviews and assessments are generally impractical in primary care.4 Brief, easy-to-complete screening tools can help clinicians identify patients with primary symptoms of PTSD.4
4-item screen assesses key characteristics of PTSD
The PC-PTSD (TABLE) is a 4-item screen that assesses the underlying characteristics specific to PTSD: re-experiencing, numbing, avoidance, and hyperarousal.4 It’s designed to be understandable to patients with an eighth-grade reading level and has been validated in a Department of Veterans Affairs (VA) primary care population (N=188).4
With a cutoff score of 3, the PCPTSD has a sensitivity of 78% and specificity of 87%, compared with the gold-standard Clinician-Administered PTSD Scale (CAPS).4 Positive responses warrant further evaluation of trauma symptoms and completion of the CAPS by a mental health provider to determine whether the patient may have PTSD or other trauma-related problems.5-7
TABLE
The primary care PTSD screen (PC-PTSD)4
| In your life, have you ever had any experience that was so frightening, horrible, or upsetting that, in the past month, you… |
| 1. Have had nightmares about it or thought about it when you did not want to? YES NO |
| 2. Tried hard not to think about it or went out of your way to avoid situations that reminded you of it? YES NO |
| 3. Were constantly on guard, watchful, or easily startled? YES NO |
| 4. Felt numb or detached from others, activities, or your surroundings? YES NO |
Breslau’s short screen addresses 7 specific symptoms
Breslau’s 7-item screening scale (available at http://ajp.psychiatryonline.org/cgi/content/full/156/6/908#T2) is another empirically tested, brief, simple means of identifying PTSD symptoms in primary care patients.2 (See also: www.pubmedcentral.nih.gov/articlerender.fcgifiartid=1484617.) Each item addresses a specific symptom.
The screen has been validated in a VA primary care clinic (N=134). With a cutoff score of 4, it has a sensitivity of 85% and specificity of 84%, yielding a positive predictive value of 71% and negative predictive value of 98%.2 The likelihood of a score <3 is 0.04 and a score >5 is 13.5. Scores of 3 to 5 have an indeterminate likelihood value (1.8). Patients with a positive screen should undergo further evaluation by a mental health provider.2
Leave lengthy screens to mental health professionals
The CAPS and the civilian version of the PTSD Symptom Checklist (PCL-C), both with 17 items, are widely used as “screens” for PTSD.7 However, their length and the recommendation that they be administered by a mental health professional make them cumbersome and impractical for use in primary care.7
Recommendations
A 2007 point-of-care guide written for primary care clinicians recommends Breslau’s short screening scale and the PCPTSD screen for use in this setting.1 Both the National Center for PTSD and Department of Defense Clinical Guidelines on PTSD recommend initial and annual screening using the PC-PTSD, PTSD Brief Screen, or Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) PTSD.8
Acknowledgements
The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the United States Air Force Medical Service or the United States Air Force at large.
1. Ebell MH. Screening instruments for post-traumatic stress disorder. Am Fam Physician. 2007;76:1848-1849.
2. Kimerling R, Ouimette P, Prins A, et al. Brief report: utility of a short screening scale for DSM-IV PTSD in primary care. J Gen Intern Med. 2006;21:65-67.
3. Screen for PTSD symptoms. PTSD core annotation E. Available at: www.oqp.med.va.gov/cpg/PTSD/PTSD_cpg/content/core/annoC.htm. Accessed April 15, 2008.
4. Prins A, Ouimette P, Kimerling R, et al. The primary care PTSD screen (PC-PTSD): development and operating characteristics. Prim Care Psychiatry. 2003;9:9-14.
5. Ouimette P, Wade M, Prins A, et al. Identifying PTSD in primary care: comparison of the primary care-PTSD screen (PC-PTSD) and the general health questionnaire-12 (GHQ). J Anxiety Disord. 2008;22:337-343.
6. National Center for PTSD. Screening for PTSD in a primary care setting. Available at: www.ncptsd.va.gov/ncmain/ncdocs/fact_shts/fs_screen_disaster.html. Accessed April 15, 2008.
7. Griffin MG, Uhlmansiek MH, Resick PA, et al. Comparison of the posttraumatic stress disorder scale versus the clinician-administered posttraumatic stress disorder scale in domestic violence survivors. J Trauma Stress. 2004;17:497-503.
8. VA/DoD clinical practice guideline for the management of post-traumatic stress. Version 1.0; January 2004. Available at: www.guideline.gov/summary/summary.aspx?ss=15&doc_id=5187. Accessed April 15, 2008.
1. Ebell MH. Screening instruments for post-traumatic stress disorder. Am Fam Physician. 2007;76:1848-1849.
2. Kimerling R, Ouimette P, Prins A, et al. Brief report: utility of a short screening scale for DSM-IV PTSD in primary care. J Gen Intern Med. 2006;21:65-67.
3. Screen for PTSD symptoms. PTSD core annotation E. Available at: www.oqp.med.va.gov/cpg/PTSD/PTSD_cpg/content/core/annoC.htm. Accessed April 15, 2008.
4. Prins A, Ouimette P, Kimerling R, et al. The primary care PTSD screen (PC-PTSD): development and operating characteristics. Prim Care Psychiatry. 2003;9:9-14.
5. Ouimette P, Wade M, Prins A, et al. Identifying PTSD in primary care: comparison of the primary care-PTSD screen (PC-PTSD) and the general health questionnaire-12 (GHQ). J Anxiety Disord. 2008;22:337-343.
6. National Center for PTSD. Screening for PTSD in a primary care setting. Available at: www.ncptsd.va.gov/ncmain/ncdocs/fact_shts/fs_screen_disaster.html. Accessed April 15, 2008.
7. Griffin MG, Uhlmansiek MH, Resick PA, et al. Comparison of the posttraumatic stress disorder scale versus the clinician-administered posttraumatic stress disorder scale in domestic violence survivors. J Trauma Stress. 2004;17:497-503.
8. VA/DoD clinical practice guideline for the management of post-traumatic stress. Version 1.0; January 2004. Available at: www.guideline.gov/summary/summary.aspx?ss=15&doc_id=5187. Accessed April 15, 2008.
Evidence-based answers from the Family Physicians Inquiries Network
Should you use steroids to treat infectious mononucleosis?
Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months (strength of recommendation [SOR]: B, 1 randomized controlled trial [RCT] and 1 nonrandomized double-blind trial). Although steroids have been shown to improve resolution of hematologic abnormalities, fever, and white blood cell count, and may shorten length of infirmary stay (SOR: B, 1 nonrandomized double-blind trial and 1 RCT), no significant difference was found in resolution of symptoms with or without steroids (SOR: A, 2 RCTs).
Do benefits sometimes outweigh risks?
Jon O. Neher, MD
Valley Medical Center Renton, Wash
Systematic reviews are good for answering broad clinical questions. In this case, the evidence clearly states that steroids have no role as routine therapy for acute mononucleosis.
But steroids do have effects (abrupt reduction in inflammation) as well as side effects. If a patient has an acute airway obstruction or a looming hospitalization for dehydration, the known therapeutic effects of steroids may suddenly appear to outweigh the potential downsides. In such specific clinical scenarios, physician and patient decision making remains guided more by extrapolations of the evidence than outcomes data.
Evidence summary
A Cochrane review of 6 relatively small (N=24-94) RCTs found insufficient evidence to support using steroids to manage infectious mononucleosis.1-7 We found no other studies.
Steroids don’t significantly reduce throat pain, weight loss
In an RCT of 40 patients, 1 dose of dexamethasone reduced throat pain at 12 hours in 60% of the treatment group, compared with placebo.2 However, no significant differences were noted at 1 and 7 days.
A trial of combined therapy with acyclovir and prednisolone in 94 patients found no differences in resolution of sore throat, weight loss, and absence from school or work in the treatment group.3 Likewise, a study of a 6-day prednisone taper found no difference in resolution of symptoms in the prednisone group (N=47).4
Conflicting findings on steroids and fever—and adverse effects
One small, double-blind study of prednisone (N=26 hospitalized college students) showed a significant difference in duration of fever and antibody titers compared with aspirin.5 Two other studies of the duration of fever didn’t find convincing evidence of benefit, however.2,7 One of these studies did find that patients’ infirmary stays were shortened an average of 3 days, although the data to support this finding were not reported.7
Two studies also reported that 3 patients experienced adverse events, including dehydration and severe pharyngitis,2 acute onset of diabetes mellitus,5 and peritonsillar cellulitis.5 Other potential adverse reactions include transient hyperglycemia, sodium retention, nausea, vomiting, and insomnia.8
Recommendations
We found no recommendations concerning the use of steroids to treat infectious mononucleosis. A review article from American Family Physician recommends avoiding corticosteroids to treat the condition unless the patient is experiencing severe complications.9
1. Candy B, Hotopf M. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst Rev. 2006;(3):CD004402.
2. Roy M, Bailey B, Amre DK, et al. Dexamethasone for the treatment of sore throat in children with suspected infectious mononucleosis: a randomized, double-blind, placebo-controlled, clinical trial. Arch Pediatr Adolesc Med. 2004;158:250-254.
3. Tynell E, Aurelius E, Brandell A, et al. Acyclovir and prednisolone treatment of acute infectious mononucleosis: a multicenter, double-blind, placebo-controlled study. J Infect Dis. 1996;174:324-331.
4. Collins M, Fleisher G, Kreisberg J, Fager S. Role of steroids in the treatment of infectious mononucleosis in the ambulatory college student. J Am Coll Health. 1984;33:101-105.
5. Bolden KJ. Corticosteroids in the treatment of infectious mononucleosis. An assessment using a double blind trial. J R Coll Gen Pract. 1972;22:87-95.
6. Klein EM, Cochran JF, Buck RL. The effects of short-term corticosteroid therapy on the symptoms of infectious mononucleosis pharyngotonsillitis: a double-blind study. J Am Coll Health Assoc. 1969;17:446-452.
7. Prout C, Dalrymple W. A double-blind study of eighty-two cases of infectious mononucleosis treated with corticosteroids. J Am Coll Health Assoc. 1966;15:62-66.
8. Adrenals: Corticosteroids general statement: Cautions. In: McEvoy GK, ed. AHFS Drug Information. Bethesda, Md: American Society of Health Systems Pharmacists; 2008.
9. Bailey RE. Diagnosis and treatment of infectious mononucleosis. Am Fam Physician. 1994;49:879-885.
Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months (strength of recommendation [SOR]: B, 1 randomized controlled trial [RCT] and 1 nonrandomized double-blind trial). Although steroids have been shown to improve resolution of hematologic abnormalities, fever, and white blood cell count, and may shorten length of infirmary stay (SOR: B, 1 nonrandomized double-blind trial and 1 RCT), no significant difference was found in resolution of symptoms with or without steroids (SOR: A, 2 RCTs).
Do benefits sometimes outweigh risks?
Jon O. Neher, MD
Valley Medical Center Renton, Wash
Systematic reviews are good for answering broad clinical questions. In this case, the evidence clearly states that steroids have no role as routine therapy for acute mononucleosis.
But steroids do have effects (abrupt reduction in inflammation) as well as side effects. If a patient has an acute airway obstruction or a looming hospitalization for dehydration, the known therapeutic effects of steroids may suddenly appear to outweigh the potential downsides. In such specific clinical scenarios, physician and patient decision making remains guided more by extrapolations of the evidence than outcomes data.
Evidence summary
A Cochrane review of 6 relatively small (N=24-94) RCTs found insufficient evidence to support using steroids to manage infectious mononucleosis.1-7 We found no other studies.
Steroids don’t significantly reduce throat pain, weight loss
In an RCT of 40 patients, 1 dose of dexamethasone reduced throat pain at 12 hours in 60% of the treatment group, compared with placebo.2 However, no significant differences were noted at 1 and 7 days.
A trial of combined therapy with acyclovir and prednisolone in 94 patients found no differences in resolution of sore throat, weight loss, and absence from school or work in the treatment group.3 Likewise, a study of a 6-day prednisone taper found no difference in resolution of symptoms in the prednisone group (N=47).4
Conflicting findings on steroids and fever—and adverse effects
One small, double-blind study of prednisone (N=26 hospitalized college students) showed a significant difference in duration of fever and antibody titers compared with aspirin.5 Two other studies of the duration of fever didn’t find convincing evidence of benefit, however.2,7 One of these studies did find that patients’ infirmary stays were shortened an average of 3 days, although the data to support this finding were not reported.7
Two studies also reported that 3 patients experienced adverse events, including dehydration and severe pharyngitis,2 acute onset of diabetes mellitus,5 and peritonsillar cellulitis.5 Other potential adverse reactions include transient hyperglycemia, sodium retention, nausea, vomiting, and insomnia.8
Recommendations
We found no recommendations concerning the use of steroids to treat infectious mononucleosis. A review article from American Family Physician recommends avoiding corticosteroids to treat the condition unless the patient is experiencing severe complications.9
Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months (strength of recommendation [SOR]: B, 1 randomized controlled trial [RCT] and 1 nonrandomized double-blind trial). Although steroids have been shown to improve resolution of hematologic abnormalities, fever, and white blood cell count, and may shorten length of infirmary stay (SOR: B, 1 nonrandomized double-blind trial and 1 RCT), no significant difference was found in resolution of symptoms with or without steroids (SOR: A, 2 RCTs).
Do benefits sometimes outweigh risks?
Jon O. Neher, MD
Valley Medical Center Renton, Wash
Systematic reviews are good for answering broad clinical questions. In this case, the evidence clearly states that steroids have no role as routine therapy for acute mononucleosis.
But steroids do have effects (abrupt reduction in inflammation) as well as side effects. If a patient has an acute airway obstruction or a looming hospitalization for dehydration, the known therapeutic effects of steroids may suddenly appear to outweigh the potential downsides. In such specific clinical scenarios, physician and patient decision making remains guided more by extrapolations of the evidence than outcomes data.
Evidence summary
A Cochrane review of 6 relatively small (N=24-94) RCTs found insufficient evidence to support using steroids to manage infectious mononucleosis.1-7 We found no other studies.
Steroids don’t significantly reduce throat pain, weight loss
In an RCT of 40 patients, 1 dose of dexamethasone reduced throat pain at 12 hours in 60% of the treatment group, compared with placebo.2 However, no significant differences were noted at 1 and 7 days.
A trial of combined therapy with acyclovir and prednisolone in 94 patients found no differences in resolution of sore throat, weight loss, and absence from school or work in the treatment group.3 Likewise, a study of a 6-day prednisone taper found no difference in resolution of symptoms in the prednisone group (N=47).4
Conflicting findings on steroids and fever—and adverse effects
One small, double-blind study of prednisone (N=26 hospitalized college students) showed a significant difference in duration of fever and antibody titers compared with aspirin.5 Two other studies of the duration of fever didn’t find convincing evidence of benefit, however.2,7 One of these studies did find that patients’ infirmary stays were shortened an average of 3 days, although the data to support this finding were not reported.7
Two studies also reported that 3 patients experienced adverse events, including dehydration and severe pharyngitis,2 acute onset of diabetes mellitus,5 and peritonsillar cellulitis.5 Other potential adverse reactions include transient hyperglycemia, sodium retention, nausea, vomiting, and insomnia.8
Recommendations
We found no recommendations concerning the use of steroids to treat infectious mononucleosis. A review article from American Family Physician recommends avoiding corticosteroids to treat the condition unless the patient is experiencing severe complications.9
1. Candy B, Hotopf M. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst Rev. 2006;(3):CD004402.
2. Roy M, Bailey B, Amre DK, et al. Dexamethasone for the treatment of sore throat in children with suspected infectious mononucleosis: a randomized, double-blind, placebo-controlled, clinical trial. Arch Pediatr Adolesc Med. 2004;158:250-254.
3. Tynell E, Aurelius E, Brandell A, et al. Acyclovir and prednisolone treatment of acute infectious mononucleosis: a multicenter, double-blind, placebo-controlled study. J Infect Dis. 1996;174:324-331.
4. Collins M, Fleisher G, Kreisberg J, Fager S. Role of steroids in the treatment of infectious mononucleosis in the ambulatory college student. J Am Coll Health. 1984;33:101-105.
5. Bolden KJ. Corticosteroids in the treatment of infectious mononucleosis. An assessment using a double blind trial. J R Coll Gen Pract. 1972;22:87-95.
6. Klein EM, Cochran JF, Buck RL. The effects of short-term corticosteroid therapy on the symptoms of infectious mononucleosis pharyngotonsillitis: a double-blind study. J Am Coll Health Assoc. 1969;17:446-452.
7. Prout C, Dalrymple W. A double-blind study of eighty-two cases of infectious mononucleosis treated with corticosteroids. J Am Coll Health Assoc. 1966;15:62-66.
8. Adrenals: Corticosteroids general statement: Cautions. In: McEvoy GK, ed. AHFS Drug Information. Bethesda, Md: American Society of Health Systems Pharmacists; 2008.
9. Bailey RE. Diagnosis and treatment of infectious mononucleosis. Am Fam Physician. 1994;49:879-885.
1. Candy B, Hotopf M. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst Rev. 2006;(3):CD004402.
2. Roy M, Bailey B, Amre DK, et al. Dexamethasone for the treatment of sore throat in children with suspected infectious mononucleosis: a randomized, double-blind, placebo-controlled, clinical trial. Arch Pediatr Adolesc Med. 2004;158:250-254.
3. Tynell E, Aurelius E, Brandell A, et al. Acyclovir and prednisolone treatment of acute infectious mononucleosis: a multicenter, double-blind, placebo-controlled study. J Infect Dis. 1996;174:324-331.
4. Collins M, Fleisher G, Kreisberg J, Fager S. Role of steroids in the treatment of infectious mononucleosis in the ambulatory college student. J Am Coll Health. 1984;33:101-105.
5. Bolden KJ. Corticosteroids in the treatment of infectious mononucleosis. An assessment using a double blind trial. J R Coll Gen Pract. 1972;22:87-95.
6. Klein EM, Cochran JF, Buck RL. The effects of short-term corticosteroid therapy on the symptoms of infectious mononucleosis pharyngotonsillitis: a double-blind study. J Am Coll Health Assoc. 1969;17:446-452.
7. Prout C, Dalrymple W. A double-blind study of eighty-two cases of infectious mononucleosis treated with corticosteroids. J Am Coll Health Assoc. 1966;15:62-66.
8. Adrenals: Corticosteroids general statement: Cautions. In: McEvoy GK, ed. AHFS Drug Information. Bethesda, Md: American Society of Health Systems Pharmacists; 2008.
9. Bailey RE. Diagnosis and treatment of infectious mononucleosis. Am Fam Physician. 1994;49:879-885.
Evidence-based answers from the Family Physicians Inquiries Network