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What is angular cheilitis and how is it treated?
Cheilitis is a broad term that describes inflammation of the lip surface characterized by dry scaling and fissuring. Specific types are atopic, angular, granulomatous, and actinic. Angular cheilitis is commonly seen in primary care settings, and it specifically refers to cheilitis that radiates from the commissures or corners of the mouth. Other terms synonymous with angular cheilitis are perlèche, commissural cheilitis, and angular stomatitis. Evidence reveals that topical ointment preparations of nystatin or amphotericin B treat angular cheilitis (strength of recommendation [SOR]: A, 2 small placebo-controlled studies).
Improving oral health through regular use of xylitol or xylitol/chlorhexidine acetate containing chewing gums decreases angular cheilitis in nursing home patients (SOR: B, 1 cluster randomized, placebo-controlled trial).
Evidence summary
There is some evidence demonstrating that antifungals effectively treat angular cheilitis. A prospective, double-blind, placebo-controlled study of 8 patients compared the efficacy of nystatin with placebo ointment. These patients were referred to a Department of Oral Diagnosis for sore lips with detected Candida albicans lesions located bilaterally.1 All of the patients were instructed to use one ointment on the right side and the other on the left side. Contamination was prevented by the use of gloves changed between applications. All 8 patients demonstrated complete healing after 1 to 4 weeks of treatment by nystatin, whereas only 1 patient had complete healing after the placebo, giving a number needed to treat (NNT) of 1.14 (P<.001).
A second study compared antifungal treatments with placebo. This randomized-controlled trial from 1975 studied lozenge use of nystatin or amphotericin B in 52 patients with red palate, angular cheilitis, or both.2 These patients were identified through screening of 600 consecutive patients attending the prosthetic clinic for examination or treatment. Patients were randomly given a 1-month supply of nystatin, amphotericin B, or placebo and instructed to dissolve 4 lozenges a day in their mouth. The study did not describe any blinding procedure. Both nystatin and amphotericin B had statistically significant cures rates at 1 month compared with placebo (P=.05 and P=0.01, respectively). The NNT was 2.7 for the nystatin group and 2.0 for the amphotericin B group at 1 month. A comparison of the 2 anti-fungals found no difference in cure rate. Recurrence rates at 2 months after discontinuing therapy were the same. The only adverse effect reported was the unpleasant taste of the lozenges, especially nystatin.
Improving oral health is another method proposed to treat angular cheilitis. Many modalities have been suggested including emphasis on denture cleaning, mouthwashes, or medicated chewing gums.
A randomized controlled, double-blind study, performed in 21 English nursing facilities, enrolled 164 patients aged 60 years and older with some natural teeth and evaluated the effects of medicated chewing gum on oral health.3 At the end of 1 year, the 111 patients (67%) completed the study. Fifty-seven percent of the participants wore dentures.
Several aspects were measured including the presence of angular cheilitis. There were 3 arms: no gum, xylitol gum, and chlorhexidine acetate/xylitol gum. The gums were used after breakfast and the evening meal and consisted of 2 pellets to be chewed for 15 minutes. Adherence was described as chewing gum at least 12 times per week for 12 months. A blinded investigator examined patients at baseline, 3, 6, 9, and 12 months.
The results demonstrated a decrease in angular cheilitis in both the xylitol and chlorhexidine acetate/xylitol group at 12 months when compared to the no gum group (P<.01). Cheilitis was found in 14% of the xylitol group (compared with 27% at baseline), 7% of the chlorhexidine acetate/xylitol group (a reduction from 28%), and 32% of the no gum group (no change). The NNT was 7.7 for the xylitol group and 4.8 for the chlorhexidine acetate/xylitol group. This effect size may be exaggerated as the study randomized by nursing home not individual patients, and there was no statistical adjustment for the cluster randomization.
Chewing gum impregnated with chlorhexidine is not readily available in the United States, whereas xylitol-containing gums are available in many retail stores and on-line centers.
Recommendations from others
We found no clinical guidelines regarding the treatment of angular cheilitis. The American Dental Association does mention topical antifungal creams for the treatment of angular cheilitis when discussing oral health and diabetes.4 In addition, Taylor’s Family Medicine recommends antifungals, including nystatin pastilles, clotrimazole troches, or a single 200-mg dose of fluconazole.5 Geriatric Medicine also recommends topical antifungals to treat angular cheilitis.6
To prevent recurrence, use xylitol gum or lip balms/petroleum jelly in the skin folds
Richard Hoffman, MD
Chesterfield Family Practice, Chesterfield, Va
Angular cheilitis is often mistakenly thought to be caused by a vitamin deficiency. As noted in this Clinical Inquiry, Candida infections in the moist skin folds around the mouth are the cause in elderly patients. The controlled trials show that antifungal preparations clearly work. In my experience, most topical anti-candidal agents work. To prevent recurrence, xylitol gum or aggressive use of lip balms or petroleum jelly in the skin folds is needed since these areas will invariably stay moist.
1. Ohman SC, Jontell M. Treatment of angular cheilitis: The significance of microbial analysis, antimicrobial treatment, and interfering factors. Acta Odontol Scand 1988;46:267-272.
2. Nairn RI. Nystatin and amphotericin B in the treatment of denture-related candidiasis. Oral Surg Oral Med Oral Pathol 1975;40:68-75.
3. Simons D, Brailsford SR, Kidd EA, Beighton D. The effects of medicated chewing gums on oral health in frail older people: a 1-year clinical trial. J Am Geriatr Soc 2002;50:1348-1353.
4. Vernillo AT. Dental considerations for the treatment of patients with diabetes mellitus. JADA 2003;134:24S-33S.
5. Taylor RB, ed. Family Medicine: Principles and Practice. 6th ed. New York: Springer; 2003.
6. Cassel CK, ed. Geriatric Medicine: An Evidence-Based Approach. 4th ed. New York: Springer; 2003.
Cheilitis is a broad term that describes inflammation of the lip surface characterized by dry scaling and fissuring. Specific types are atopic, angular, granulomatous, and actinic. Angular cheilitis is commonly seen in primary care settings, and it specifically refers to cheilitis that radiates from the commissures or corners of the mouth. Other terms synonymous with angular cheilitis are perlèche, commissural cheilitis, and angular stomatitis. Evidence reveals that topical ointment preparations of nystatin or amphotericin B treat angular cheilitis (strength of recommendation [SOR]: A, 2 small placebo-controlled studies).
Improving oral health through regular use of xylitol or xylitol/chlorhexidine acetate containing chewing gums decreases angular cheilitis in nursing home patients (SOR: B, 1 cluster randomized, placebo-controlled trial).
Evidence summary
There is some evidence demonstrating that antifungals effectively treat angular cheilitis. A prospective, double-blind, placebo-controlled study of 8 patients compared the efficacy of nystatin with placebo ointment. These patients were referred to a Department of Oral Diagnosis for sore lips with detected Candida albicans lesions located bilaterally.1 All of the patients were instructed to use one ointment on the right side and the other on the left side. Contamination was prevented by the use of gloves changed between applications. All 8 patients demonstrated complete healing after 1 to 4 weeks of treatment by nystatin, whereas only 1 patient had complete healing after the placebo, giving a number needed to treat (NNT) of 1.14 (P<.001).
A second study compared antifungal treatments with placebo. This randomized-controlled trial from 1975 studied lozenge use of nystatin or amphotericin B in 52 patients with red palate, angular cheilitis, or both.2 These patients were identified through screening of 600 consecutive patients attending the prosthetic clinic for examination or treatment. Patients were randomly given a 1-month supply of nystatin, amphotericin B, or placebo and instructed to dissolve 4 lozenges a day in their mouth. The study did not describe any blinding procedure. Both nystatin and amphotericin B had statistically significant cures rates at 1 month compared with placebo (P=.05 and P=0.01, respectively). The NNT was 2.7 for the nystatin group and 2.0 for the amphotericin B group at 1 month. A comparison of the 2 anti-fungals found no difference in cure rate. Recurrence rates at 2 months after discontinuing therapy were the same. The only adverse effect reported was the unpleasant taste of the lozenges, especially nystatin.
Improving oral health is another method proposed to treat angular cheilitis. Many modalities have been suggested including emphasis on denture cleaning, mouthwashes, or medicated chewing gums.
A randomized controlled, double-blind study, performed in 21 English nursing facilities, enrolled 164 patients aged 60 years and older with some natural teeth and evaluated the effects of medicated chewing gum on oral health.3 At the end of 1 year, the 111 patients (67%) completed the study. Fifty-seven percent of the participants wore dentures.
Several aspects were measured including the presence of angular cheilitis. There were 3 arms: no gum, xylitol gum, and chlorhexidine acetate/xylitol gum. The gums were used after breakfast and the evening meal and consisted of 2 pellets to be chewed for 15 minutes. Adherence was described as chewing gum at least 12 times per week for 12 months. A blinded investigator examined patients at baseline, 3, 6, 9, and 12 months.
The results demonstrated a decrease in angular cheilitis in both the xylitol and chlorhexidine acetate/xylitol group at 12 months when compared to the no gum group (P<.01). Cheilitis was found in 14% of the xylitol group (compared with 27% at baseline), 7% of the chlorhexidine acetate/xylitol group (a reduction from 28%), and 32% of the no gum group (no change). The NNT was 7.7 for the xylitol group and 4.8 for the chlorhexidine acetate/xylitol group. This effect size may be exaggerated as the study randomized by nursing home not individual patients, and there was no statistical adjustment for the cluster randomization.
Chewing gum impregnated with chlorhexidine is not readily available in the United States, whereas xylitol-containing gums are available in many retail stores and on-line centers.
Recommendations from others
We found no clinical guidelines regarding the treatment of angular cheilitis. The American Dental Association does mention topical antifungal creams for the treatment of angular cheilitis when discussing oral health and diabetes.4 In addition, Taylor’s Family Medicine recommends antifungals, including nystatin pastilles, clotrimazole troches, or a single 200-mg dose of fluconazole.5 Geriatric Medicine also recommends topical antifungals to treat angular cheilitis.6
To prevent recurrence, use xylitol gum or lip balms/petroleum jelly in the skin folds
Richard Hoffman, MD
Chesterfield Family Practice, Chesterfield, Va
Angular cheilitis is often mistakenly thought to be caused by a vitamin deficiency. As noted in this Clinical Inquiry, Candida infections in the moist skin folds around the mouth are the cause in elderly patients. The controlled trials show that antifungal preparations clearly work. In my experience, most topical anti-candidal agents work. To prevent recurrence, xylitol gum or aggressive use of lip balms or petroleum jelly in the skin folds is needed since these areas will invariably stay moist.
Cheilitis is a broad term that describes inflammation of the lip surface characterized by dry scaling and fissuring. Specific types are atopic, angular, granulomatous, and actinic. Angular cheilitis is commonly seen in primary care settings, and it specifically refers to cheilitis that radiates from the commissures or corners of the mouth. Other terms synonymous with angular cheilitis are perlèche, commissural cheilitis, and angular stomatitis. Evidence reveals that topical ointment preparations of nystatin or amphotericin B treat angular cheilitis (strength of recommendation [SOR]: A, 2 small placebo-controlled studies).
Improving oral health through regular use of xylitol or xylitol/chlorhexidine acetate containing chewing gums decreases angular cheilitis in nursing home patients (SOR: B, 1 cluster randomized, placebo-controlled trial).
Evidence summary
There is some evidence demonstrating that antifungals effectively treat angular cheilitis. A prospective, double-blind, placebo-controlled study of 8 patients compared the efficacy of nystatin with placebo ointment. These patients were referred to a Department of Oral Diagnosis for sore lips with detected Candida albicans lesions located bilaterally.1 All of the patients were instructed to use one ointment on the right side and the other on the left side. Contamination was prevented by the use of gloves changed between applications. All 8 patients demonstrated complete healing after 1 to 4 weeks of treatment by nystatin, whereas only 1 patient had complete healing after the placebo, giving a number needed to treat (NNT) of 1.14 (P<.001).
A second study compared antifungal treatments with placebo. This randomized-controlled trial from 1975 studied lozenge use of nystatin or amphotericin B in 52 patients with red palate, angular cheilitis, or both.2 These patients were identified through screening of 600 consecutive patients attending the prosthetic clinic for examination or treatment. Patients were randomly given a 1-month supply of nystatin, amphotericin B, or placebo and instructed to dissolve 4 lozenges a day in their mouth. The study did not describe any blinding procedure. Both nystatin and amphotericin B had statistically significant cures rates at 1 month compared with placebo (P=.05 and P=0.01, respectively). The NNT was 2.7 for the nystatin group and 2.0 for the amphotericin B group at 1 month. A comparison of the 2 anti-fungals found no difference in cure rate. Recurrence rates at 2 months after discontinuing therapy were the same. The only adverse effect reported was the unpleasant taste of the lozenges, especially nystatin.
Improving oral health is another method proposed to treat angular cheilitis. Many modalities have been suggested including emphasis on denture cleaning, mouthwashes, or medicated chewing gums.
A randomized controlled, double-blind study, performed in 21 English nursing facilities, enrolled 164 patients aged 60 years and older with some natural teeth and evaluated the effects of medicated chewing gum on oral health.3 At the end of 1 year, the 111 patients (67%) completed the study. Fifty-seven percent of the participants wore dentures.
Several aspects were measured including the presence of angular cheilitis. There were 3 arms: no gum, xylitol gum, and chlorhexidine acetate/xylitol gum. The gums were used after breakfast and the evening meal and consisted of 2 pellets to be chewed for 15 minutes. Adherence was described as chewing gum at least 12 times per week for 12 months. A blinded investigator examined patients at baseline, 3, 6, 9, and 12 months.
The results demonstrated a decrease in angular cheilitis in both the xylitol and chlorhexidine acetate/xylitol group at 12 months when compared to the no gum group (P<.01). Cheilitis was found in 14% of the xylitol group (compared with 27% at baseline), 7% of the chlorhexidine acetate/xylitol group (a reduction from 28%), and 32% of the no gum group (no change). The NNT was 7.7 for the xylitol group and 4.8 for the chlorhexidine acetate/xylitol group. This effect size may be exaggerated as the study randomized by nursing home not individual patients, and there was no statistical adjustment for the cluster randomization.
Chewing gum impregnated with chlorhexidine is not readily available in the United States, whereas xylitol-containing gums are available in many retail stores and on-line centers.
Recommendations from others
We found no clinical guidelines regarding the treatment of angular cheilitis. The American Dental Association does mention topical antifungal creams for the treatment of angular cheilitis when discussing oral health and diabetes.4 In addition, Taylor’s Family Medicine recommends antifungals, including nystatin pastilles, clotrimazole troches, or a single 200-mg dose of fluconazole.5 Geriatric Medicine also recommends topical antifungals to treat angular cheilitis.6
To prevent recurrence, use xylitol gum or lip balms/petroleum jelly in the skin folds
Richard Hoffman, MD
Chesterfield Family Practice, Chesterfield, Va
Angular cheilitis is often mistakenly thought to be caused by a vitamin deficiency. As noted in this Clinical Inquiry, Candida infections in the moist skin folds around the mouth are the cause in elderly patients. The controlled trials show that antifungal preparations clearly work. In my experience, most topical anti-candidal agents work. To prevent recurrence, xylitol gum or aggressive use of lip balms or petroleum jelly in the skin folds is needed since these areas will invariably stay moist.
1. Ohman SC, Jontell M. Treatment of angular cheilitis: The significance of microbial analysis, antimicrobial treatment, and interfering factors. Acta Odontol Scand 1988;46:267-272.
2. Nairn RI. Nystatin and amphotericin B in the treatment of denture-related candidiasis. Oral Surg Oral Med Oral Pathol 1975;40:68-75.
3. Simons D, Brailsford SR, Kidd EA, Beighton D. The effects of medicated chewing gums on oral health in frail older people: a 1-year clinical trial. J Am Geriatr Soc 2002;50:1348-1353.
4. Vernillo AT. Dental considerations for the treatment of patients with diabetes mellitus. JADA 2003;134:24S-33S.
5. Taylor RB, ed. Family Medicine: Principles and Practice. 6th ed. New York: Springer; 2003.
6. Cassel CK, ed. Geriatric Medicine: An Evidence-Based Approach. 4th ed. New York: Springer; 2003.
1. Ohman SC, Jontell M. Treatment of angular cheilitis: The significance of microbial analysis, antimicrobial treatment, and interfering factors. Acta Odontol Scand 1988;46:267-272.
2. Nairn RI. Nystatin and amphotericin B in the treatment of denture-related candidiasis. Oral Surg Oral Med Oral Pathol 1975;40:68-75.
3. Simons D, Brailsford SR, Kidd EA, Beighton D. The effects of medicated chewing gums on oral health in frail older people: a 1-year clinical trial. J Am Geriatr Soc 2002;50:1348-1353.
4. Vernillo AT. Dental considerations for the treatment of patients with diabetes mellitus. JADA 2003;134:24S-33S.
5. Taylor RB, ed. Family Medicine: Principles and Practice. 6th ed. New York: Springer; 2003.
6. Cassel CK, ed. Geriatric Medicine: An Evidence-Based Approach. 4th ed. New York: Springer; 2003.
Evidence-based answers from the Family Physicians Inquiries Network
How should we treat chronic daily headache when conservative measures fail?
For the purposes of this review, we considered conservative measures to include such therapies as nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and acetaminophen with codeine. Amitriptyline is the best-supported option for the treatment of chronic daily headaches for those patients who have not been treated by conservative measures (strength of recommendation [SOR]: A, based on a meta-analysis of randomized controlled trials [RCTs]).1
For patients who overuse symptomatic headache medications, medication withdrawal is effective (SOR: B,based on a systematic review of cohort and case-control studies).2 Additional therapies include other tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and prophylactic treatments for migraine (SOR: B).3
Evidence summary
Chronic daily headache is a heterogeneous primary headache disorder, often defined as a headache duration of more than 4 hours and a headache frequency of more than 15 per month; it affects less than 5% of the US population. Four headache subtypes included in the chronic daily headache definition are chronic (transformed) migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Each subtype may be associated with medication overuse.4
Chronic daily headache is challenging to categorize and difficult to manage, and scientific evidence to guide treatment is scant. Despite this, a few studies do offer some hopeful alternatives to those patients who have had conservative measures fail (Table).
A meta-analysis from 2001 reviewed 38 RCTs of antidepressants as prophylaxis for chronic headache. Nineteen studies investigated TCAs, 18 examined serotonin blockers, and 7 focused on SSRIs. Patients taking antidepressants were twice as likely to report headache improvement (rate ratio [RR]=2.0; 95% confidence interval [CI], 1.6–2.4), with the average amount of improvement considered to be large (standard mean difference=0.94; 95% CI, 0.65–1.2). Serotonin blockers, most of which are not available or commonly used in the US, and TCAs were all effective in decreasing the headache burden, while the results for SSRIs were less clear. Dosages of amitriptyline ranged from 10 to 150 mg daily; most of the studies used 60 to 100 mg daily.1
Medication withdrawal therapy is a treatment strategy for chronic daily headaches associated with the paradoxical induction of headaches by the frequent, long-term use of immediate relief medications such as aspirin, NSAIDs, acetaminophen, caffeine, codeine, ergotamine, and sumatriptan. A retrospective study tracked 101 men and women who underwent a controlled outpatient withdrawal of their overused medications. Headache diaries kept for 1 to 3 months reflected that 56% of the patients had at least a 50% reduction in headache days after removal of overused drugs. Twenty-two patients who had no success with withdrawal and continued to have headaches were treated with amitriptyline. Subsequently, 10 of these patients experienced a 50% reduction in headache frequency.5
A systematic review of the therapeutic approaches to medication-induced headache looked at 18 studies from 1966 to 1998. Although most were uncontrolled small trials, medically monitored withdrawal of all symptomatic headache medications is recommended by the authors. No long-term outcome comparisons between withdrawal strategies are available.2
Other therapies for treating chronic daily headache include the skeletal muscle relaxant tizanidine (Zanaflex), which was studied in an industry-sponsored, double-blind, placebo-controlled trial of 92 patients. The medication was used as prophylaxis, titrating up to a dose of 8 mg 3 times daily. The overall headache index (a measure of headache intensity, frequency, and duration) significantly decreased. The headache index decreased in the tizanidine group from 2.6 to 1.2, and in the placebo group from 2.6 to 2.1 (P =.0025). Decreases in headache frequency and headache intensity were less dramatic but still significant. This trial lasted only 12 weeks, so longer-term outcomes are not available.6
Stress management, acupuncture, botulinum toxin, behavioral therapy including relaxation therapy, biofeedback, and even Internet-based self-help have all been studied, but most of these therapies do not have significant evidence-based support.
TABLE
Treatment options for chronic daily headache
| Treatment option | Study design, no. of studies | Total no. enrolled | Outcome |
|---|---|---|---|
| Amitriptyline | Double-blind, 7 | 257 | ↓ in headache severity, frequency and/or duration |
| Fluoxetine | Double-blind, 2 | 92 | ↑ in headache-free days, mood improvement;↓ in headache severity |
| Gabapentin | Double-blind, 1 | 26 | ↓ in headache frequency |
| Botulinum toxin A | Double-blind, 1 | 16 | ↓ in headache intensity, frequency and duration |
| Tizanidine | Double-blind, 1 | 45 | ↓ in headache intensity, frequency and daily analgesic use |
| Sumatriptan | Double-blind,1 | 42 | No statistically significant change in headache intensity |
| Valproate | Open, 5 | 191 | Mixed results |
| Adapted from Redillas and Solomon 2000.3 | |||
Recommendations from others
Our literature search and review of major textbooks found no formally organized guidelines or recommendations on the treatment of chronic daily headache.
A detailed history and assessment of possible comorbid conditions is crucial
Pouran Yousefi, MD
Baylor College of Medicine, Houston, Tex
Obtaining a detailed history and the assessment of possible comorbid conditions such as psychiatric disorders, insomnia, and existing stressors is crucial to making the diagnosis of chronic daily headache and choosing therapy. A headache diary provides clinicians with helpful information such as the duration and frequency of the headaches, possible triggering factors, and the class, and numbers of analgesics used. Patients who have more than 2 episodes of migraine per week are appropriate candidates for preventive treatment.
The possibility of analgesic overuse must be considered for patients who use headache medications more than twice a week. Preventive headache medications do not work if analgesics are being overused. Once a diagnosis is made, detoxification needs to be discussed with the patient.
As a patient with chronic migraine, I have found stretching exercise, stress management, and dietary modifications very helpful. The most common foods to avoid are caffeine, chocolate, alcohol, aged or cured meat, bananas, and foods containing monosodium glutamate or tyramine.3
1. Tomkins GE, Jackson JL, O’Malley PG, Balden E, Santoro JE. Treatment of chronic headache with anti-depressants: a meta-analysis. Am J Med 2001;111:54-63.
2. Zed PJ, Loewen PS, Robinson G. Medication-induced headache: overview and systematic review of therapeutic approaches. Ann Pharmacother 1999;33:61-72.
3. Redillas C, Solomon S. Prophylactic pharmacological treatment of chronic daily headache. Headache 2000;40:83-102.
4. Levin M. Chronic daily headache and the revised international headache society classification. Curr Pain Headache Rep 2004;8:59-65.
5. Linton-Dahlöf P, Linde M, Dahlöf C. Withdrawal therapy improves chronic daily headache associated with long-term misuse of headache medication: a retrospective study. Cephalalgia 2000;20:658-662.
6. Saper JR, Lake AE, 3rd, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study. Headache 2002;42:470-482.
For the purposes of this review, we considered conservative measures to include such therapies as nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and acetaminophen with codeine. Amitriptyline is the best-supported option for the treatment of chronic daily headaches for those patients who have not been treated by conservative measures (strength of recommendation [SOR]: A, based on a meta-analysis of randomized controlled trials [RCTs]).1
For patients who overuse symptomatic headache medications, medication withdrawal is effective (SOR: B,based on a systematic review of cohort and case-control studies).2 Additional therapies include other tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and prophylactic treatments for migraine (SOR: B).3
Evidence summary
Chronic daily headache is a heterogeneous primary headache disorder, often defined as a headache duration of more than 4 hours and a headache frequency of more than 15 per month; it affects less than 5% of the US population. Four headache subtypes included in the chronic daily headache definition are chronic (transformed) migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Each subtype may be associated with medication overuse.4
Chronic daily headache is challenging to categorize and difficult to manage, and scientific evidence to guide treatment is scant. Despite this, a few studies do offer some hopeful alternatives to those patients who have had conservative measures fail (Table).
A meta-analysis from 2001 reviewed 38 RCTs of antidepressants as prophylaxis for chronic headache. Nineteen studies investigated TCAs, 18 examined serotonin blockers, and 7 focused on SSRIs. Patients taking antidepressants were twice as likely to report headache improvement (rate ratio [RR]=2.0; 95% confidence interval [CI], 1.6–2.4), with the average amount of improvement considered to be large (standard mean difference=0.94; 95% CI, 0.65–1.2). Serotonin blockers, most of which are not available or commonly used in the US, and TCAs were all effective in decreasing the headache burden, while the results for SSRIs were less clear. Dosages of amitriptyline ranged from 10 to 150 mg daily; most of the studies used 60 to 100 mg daily.1
Medication withdrawal therapy is a treatment strategy for chronic daily headaches associated with the paradoxical induction of headaches by the frequent, long-term use of immediate relief medications such as aspirin, NSAIDs, acetaminophen, caffeine, codeine, ergotamine, and sumatriptan. A retrospective study tracked 101 men and women who underwent a controlled outpatient withdrawal of their overused medications. Headache diaries kept for 1 to 3 months reflected that 56% of the patients had at least a 50% reduction in headache days after removal of overused drugs. Twenty-two patients who had no success with withdrawal and continued to have headaches were treated with amitriptyline. Subsequently, 10 of these patients experienced a 50% reduction in headache frequency.5
A systematic review of the therapeutic approaches to medication-induced headache looked at 18 studies from 1966 to 1998. Although most were uncontrolled small trials, medically monitored withdrawal of all symptomatic headache medications is recommended by the authors. No long-term outcome comparisons between withdrawal strategies are available.2
Other therapies for treating chronic daily headache include the skeletal muscle relaxant tizanidine (Zanaflex), which was studied in an industry-sponsored, double-blind, placebo-controlled trial of 92 patients. The medication was used as prophylaxis, titrating up to a dose of 8 mg 3 times daily. The overall headache index (a measure of headache intensity, frequency, and duration) significantly decreased. The headache index decreased in the tizanidine group from 2.6 to 1.2, and in the placebo group from 2.6 to 2.1 (P =.0025). Decreases in headache frequency and headache intensity were less dramatic but still significant. This trial lasted only 12 weeks, so longer-term outcomes are not available.6
Stress management, acupuncture, botulinum toxin, behavioral therapy including relaxation therapy, biofeedback, and even Internet-based self-help have all been studied, but most of these therapies do not have significant evidence-based support.
TABLE
Treatment options for chronic daily headache
| Treatment option | Study design, no. of studies | Total no. enrolled | Outcome |
|---|---|---|---|
| Amitriptyline | Double-blind, 7 | 257 | ↓ in headache severity, frequency and/or duration |
| Fluoxetine | Double-blind, 2 | 92 | ↑ in headache-free days, mood improvement;↓ in headache severity |
| Gabapentin | Double-blind, 1 | 26 | ↓ in headache frequency |
| Botulinum toxin A | Double-blind, 1 | 16 | ↓ in headache intensity, frequency and duration |
| Tizanidine | Double-blind, 1 | 45 | ↓ in headache intensity, frequency and daily analgesic use |
| Sumatriptan | Double-blind,1 | 42 | No statistically significant change in headache intensity |
| Valproate | Open, 5 | 191 | Mixed results |
| Adapted from Redillas and Solomon 2000.3 | |||
Recommendations from others
Our literature search and review of major textbooks found no formally organized guidelines or recommendations on the treatment of chronic daily headache.
A detailed history and assessment of possible comorbid conditions is crucial
Pouran Yousefi, MD
Baylor College of Medicine, Houston, Tex
Obtaining a detailed history and the assessment of possible comorbid conditions such as psychiatric disorders, insomnia, and existing stressors is crucial to making the diagnosis of chronic daily headache and choosing therapy. A headache diary provides clinicians with helpful information such as the duration and frequency of the headaches, possible triggering factors, and the class, and numbers of analgesics used. Patients who have more than 2 episodes of migraine per week are appropriate candidates for preventive treatment.
The possibility of analgesic overuse must be considered for patients who use headache medications more than twice a week. Preventive headache medications do not work if analgesics are being overused. Once a diagnosis is made, detoxification needs to be discussed with the patient.
As a patient with chronic migraine, I have found stretching exercise, stress management, and dietary modifications very helpful. The most common foods to avoid are caffeine, chocolate, alcohol, aged or cured meat, bananas, and foods containing monosodium glutamate or tyramine.3
For the purposes of this review, we considered conservative measures to include such therapies as nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and acetaminophen with codeine. Amitriptyline is the best-supported option for the treatment of chronic daily headaches for those patients who have not been treated by conservative measures (strength of recommendation [SOR]: A, based on a meta-analysis of randomized controlled trials [RCTs]).1
For patients who overuse symptomatic headache medications, medication withdrawal is effective (SOR: B,based on a systematic review of cohort and case-control studies).2 Additional therapies include other tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and prophylactic treatments for migraine (SOR: B).3
Evidence summary
Chronic daily headache is a heterogeneous primary headache disorder, often defined as a headache duration of more than 4 hours and a headache frequency of more than 15 per month; it affects less than 5% of the US population. Four headache subtypes included in the chronic daily headache definition are chronic (transformed) migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Each subtype may be associated with medication overuse.4
Chronic daily headache is challenging to categorize and difficult to manage, and scientific evidence to guide treatment is scant. Despite this, a few studies do offer some hopeful alternatives to those patients who have had conservative measures fail (Table).
A meta-analysis from 2001 reviewed 38 RCTs of antidepressants as prophylaxis for chronic headache. Nineteen studies investigated TCAs, 18 examined serotonin blockers, and 7 focused on SSRIs. Patients taking antidepressants were twice as likely to report headache improvement (rate ratio [RR]=2.0; 95% confidence interval [CI], 1.6–2.4), with the average amount of improvement considered to be large (standard mean difference=0.94; 95% CI, 0.65–1.2). Serotonin blockers, most of which are not available or commonly used in the US, and TCAs were all effective in decreasing the headache burden, while the results for SSRIs were less clear. Dosages of amitriptyline ranged from 10 to 150 mg daily; most of the studies used 60 to 100 mg daily.1
Medication withdrawal therapy is a treatment strategy for chronic daily headaches associated with the paradoxical induction of headaches by the frequent, long-term use of immediate relief medications such as aspirin, NSAIDs, acetaminophen, caffeine, codeine, ergotamine, and sumatriptan. A retrospective study tracked 101 men and women who underwent a controlled outpatient withdrawal of their overused medications. Headache diaries kept for 1 to 3 months reflected that 56% of the patients had at least a 50% reduction in headache days after removal of overused drugs. Twenty-two patients who had no success with withdrawal and continued to have headaches were treated with amitriptyline. Subsequently, 10 of these patients experienced a 50% reduction in headache frequency.5
A systematic review of the therapeutic approaches to medication-induced headache looked at 18 studies from 1966 to 1998. Although most were uncontrolled small trials, medically monitored withdrawal of all symptomatic headache medications is recommended by the authors. No long-term outcome comparisons between withdrawal strategies are available.2
Other therapies for treating chronic daily headache include the skeletal muscle relaxant tizanidine (Zanaflex), which was studied in an industry-sponsored, double-blind, placebo-controlled trial of 92 patients. The medication was used as prophylaxis, titrating up to a dose of 8 mg 3 times daily. The overall headache index (a measure of headache intensity, frequency, and duration) significantly decreased. The headache index decreased in the tizanidine group from 2.6 to 1.2, and in the placebo group from 2.6 to 2.1 (P =.0025). Decreases in headache frequency and headache intensity were less dramatic but still significant. This trial lasted only 12 weeks, so longer-term outcomes are not available.6
Stress management, acupuncture, botulinum toxin, behavioral therapy including relaxation therapy, biofeedback, and even Internet-based self-help have all been studied, but most of these therapies do not have significant evidence-based support.
TABLE
Treatment options for chronic daily headache
| Treatment option | Study design, no. of studies | Total no. enrolled | Outcome |
|---|---|---|---|
| Amitriptyline | Double-blind, 7 | 257 | ↓ in headache severity, frequency and/or duration |
| Fluoxetine | Double-blind, 2 | 92 | ↑ in headache-free days, mood improvement;↓ in headache severity |
| Gabapentin | Double-blind, 1 | 26 | ↓ in headache frequency |
| Botulinum toxin A | Double-blind, 1 | 16 | ↓ in headache intensity, frequency and duration |
| Tizanidine | Double-blind, 1 | 45 | ↓ in headache intensity, frequency and daily analgesic use |
| Sumatriptan | Double-blind,1 | 42 | No statistically significant change in headache intensity |
| Valproate | Open, 5 | 191 | Mixed results |
| Adapted from Redillas and Solomon 2000.3 | |||
Recommendations from others
Our literature search and review of major textbooks found no formally organized guidelines or recommendations on the treatment of chronic daily headache.
A detailed history and assessment of possible comorbid conditions is crucial
Pouran Yousefi, MD
Baylor College of Medicine, Houston, Tex
Obtaining a detailed history and the assessment of possible comorbid conditions such as psychiatric disorders, insomnia, and existing stressors is crucial to making the diagnosis of chronic daily headache and choosing therapy. A headache diary provides clinicians with helpful information such as the duration and frequency of the headaches, possible triggering factors, and the class, and numbers of analgesics used. Patients who have more than 2 episodes of migraine per week are appropriate candidates for preventive treatment.
The possibility of analgesic overuse must be considered for patients who use headache medications more than twice a week. Preventive headache medications do not work if analgesics are being overused. Once a diagnosis is made, detoxification needs to be discussed with the patient.
As a patient with chronic migraine, I have found stretching exercise, stress management, and dietary modifications very helpful. The most common foods to avoid are caffeine, chocolate, alcohol, aged or cured meat, bananas, and foods containing monosodium glutamate or tyramine.3
1. Tomkins GE, Jackson JL, O’Malley PG, Balden E, Santoro JE. Treatment of chronic headache with anti-depressants: a meta-analysis. Am J Med 2001;111:54-63.
2. Zed PJ, Loewen PS, Robinson G. Medication-induced headache: overview and systematic review of therapeutic approaches. Ann Pharmacother 1999;33:61-72.
3. Redillas C, Solomon S. Prophylactic pharmacological treatment of chronic daily headache. Headache 2000;40:83-102.
4. Levin M. Chronic daily headache and the revised international headache society classification. Curr Pain Headache Rep 2004;8:59-65.
5. Linton-Dahlöf P, Linde M, Dahlöf C. Withdrawal therapy improves chronic daily headache associated with long-term misuse of headache medication: a retrospective study. Cephalalgia 2000;20:658-662.
6. Saper JR, Lake AE, 3rd, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study. Headache 2002;42:470-482.
1. Tomkins GE, Jackson JL, O’Malley PG, Balden E, Santoro JE. Treatment of chronic headache with anti-depressants: a meta-analysis. Am J Med 2001;111:54-63.
2. Zed PJ, Loewen PS, Robinson G. Medication-induced headache: overview and systematic review of therapeutic approaches. Ann Pharmacother 1999;33:61-72.
3. Redillas C, Solomon S. Prophylactic pharmacological treatment of chronic daily headache. Headache 2000;40:83-102.
4. Levin M. Chronic daily headache and the revised international headache society classification. Curr Pain Headache Rep 2004;8:59-65.
5. Linton-Dahlöf P, Linde M, Dahlöf C. Withdrawal therapy improves chronic daily headache associated with long-term misuse of headache medication: a retrospective study. Cephalalgia 2000;20:658-662.
6. Saper JR, Lake AE, 3rd, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study. Headache 2002;42:470-482.
Evidence-based answers from the Family Physicians Inquiries Network