A 72-year-old man presented to his primary care provider’s office with complaints of peeling skin on his penis and frequent, burning urination. He said he had first noticed redness on his penis about four days earlier, adding that it was growing worse. He was unsure whether he was truly experiencing frequent urination or just more aware of urinating because of the burning pain. He reported no attempts to treat himself, stating that he was “just keeping an eye on it and hoping it would go away.”

The patient’s medical history was limited to hypertension, for which he was taking valsartan, and allergies, for which he took fexofenadine. His surgical history included a tonsillectomy and appendectomy during his early teens. He had no known allergies to any medications.

The patient was married and retired after an executive career. He and his wife split their residence between New York and Florida during seasonal changes and were living in Florida at the time. He reported social drinking (“on rare occasions, these days”) and smoking an occasional cigar. He reported that he showers only once or twice weekly because of dry skin.

The following vital signs were recorded: blood pressure, 110/72 mm Hg; heart rate, 68 beats/min; respirations, 15/min; temperature, 97.8°F; and O2 saturation, 99% on room air. He was 73” tall and weighed 197 lb, with a BMI of 26.

The patient was alert and oriented. His physical exam was overall unremarkable, with the exception of an uncircumcised penis with redness and inflammation on the glans penis and no discharge noted. The reddened area was bright and shiny with a moist appearance and well-defined borders. The man denied any risk for sexually transmitted disease (STD) and denied any penile discharge. He also denied fever, chills, or arthritis.

Urinalysis performed in the office was negative for a urinary tract infection or for elevated glucose. A laboratory report from six months earlier was reviewed; all findings were within normal range, including the blood glucose level, with special attention paid for possible underlying cause; and the prostate-specific antigen (PSA) level, obtained for possible prostatitis or prostate cancer.

The differential diagnosis included eczema or psoriasis, Zoon’s balanitis, penile cancer, balanitis xerotica obliterans (lichen sclerosus), candidiasis balanitis, and circinate balanitis (as occurs in patients with Reiter’s disease; see table^1-5). The absence of circumcision and the patient’s report of infrequent bathing raised concern for a hygiene-related etiology; the final diagnosis, made empirically, was candidiasis balanitis. Regarding an underlying cause, the laboratory order included a urine culture, fasting complete blood count, chemistry panel, and PSA level.

The patient was given instructions to wash the affected area twice daily for one week with a lukewarm weak saline solution (1 tablespoon salt/L water),^5,6 gently retracting the foreskin; he was also given a topical antifungal cream⁷ (ketoconazole 2%, although other choices are discussed below), to be applied two to three times daily until his symptoms resolved.⁶ He was advised to return in one week if the condition did not improve or grew worse⁵; referral to dermatology would then be considered. The patient was also advised that in the case of a recurrent episode, dermatology would be consulted. The possibility of circumcision was discussed,⁸ and the patient was given information about the procedure, with referral to a urologist in the area.

Discussion

Balanitis is an inflammation of the glans penis; balanoposthitis involves the foreskin and prepuce.^9-11 Balanitis can occur in men of any age, with etiologies varying with a patient’s age. Typical signs and symptoms include redness and swelling of the glans penis or foreskin, itching and/or pain, urethral discharge, phimosis, swollen lymph nodes, ulceration or plaque appearance, and pain on urination.¹²

In addition to the differential diagnoses mentioned, several additional conditions can be considered in a man with penile lesions. In older men, it is particularly important to investigate such lesions thoroughly, following the patient until the underlying cause is determined and the best treatment choice is selected. Specialists in dermatology and urology can best identify persistent or chronic lesions and make appropriate treatment recommendations, including possible circumcision.

The condition is commonly associated with absence of circumcision, poor hygiene, and phimosis (the inability to retract the foreskin from the glans penis). Accumulation of glandular secretions (smegma) and sloughed epithelial cells under the foreskin can lead to irritation and subsequent infection.

Uncontrolled or poorly controlled diabetes can be implicated in candidiasis infections.¹ Other causes and contributing factors include chemical irritants (eg, soaps, lubricating jelly), edematous conditions (including congestive heart failure, cirrhosis, and nephrosis), drug allergies, morbid obesity, and a number of viruses and other pathogens, including those associated with STDs.¹²

A more detailed laboratory work-up might include the following:

• Serum glucose test (as part of a diabetes screening; in older men, this inflammatory condition can be a presenting sign of diabetes mellitus⁶)

• Culture of discharge, if any is present

• Serology test for STDs

• Wet mount with potassium hydroxide (for Candida albicans infection)

• Ultrasound, in severe cases or when urinary obstruction is suspected.

Additionally, in chronic cases, the patient should be referred to dermatology or urology for biopsy.^5,9 Testing for anaerobes should also be considered for the patient and his sexual partner; if results are positive, treatment with oral metronidazole (400 mg tid for 10 days) is advised.⁶

In this patient’s case, the test that would best support an in-office diagnosis of candidiasis balanitis is a wet mount with potassium hydroxide. This was not performed at the time of the case patient’s visit, however; the diagnosis was empirically determined.

Management, Including Patient Education

Treatment of candidiasis balanitis involves routinely cleaning the penis and foreskin, as the case patient was instructed; use of soap, an irritant, should be avoided until the condition is resolved.^7,10 Appropriate topical antifungal creams include nystatin, ketoconazole, miconazole, clotrimazole, econazole, and terbinafine, applied two to three times daily for at least 10 days; a cream combining an imidazole with 1% hydrocortisone may be effective for patients with significant inflammation.^5,6,8,10,13

The patient should be instructed to:

• Keep the area clean and dry

• Wash twice daily with weak saline solution after removing residual medication and before applying fresh medication

• Wear loose cotton underwear

• Avoid sharing towels or cleaning cloths

• Wash personal items and surfaces, if possible, with disinfectant

• Notify sexual partner(s) that they may need treatment

• Discontinue sexual intercourse until infection is resolved

• Continue treatment for 10 to 14 days, even though relief may occur early

• Follow up with the clinician if no improvement is seen within one week

• Consider circumcision, in case of chronic infection.^1,2,8,12

Conclusion

It is important to diagnose balanitis correctly, as this condition can affect sexual and urinary function, and its effects should not be underestimated in older men. Differentiating between infectious, noninfectious, premalignant, and malignant lesions will lead to appropriate care and allow early diagnosis or prevention of curable malignancies.

A 72-year-old man presented to his primary care provider’s office with complaints of peeling skin on his penis and frequent, burning urination. He said he had first noticed redness on his penis about four days earlier, adding that it was growing worse. He was unsure whether he was truly experiencing frequent urination or just more aware of urinating because of the burning pain. He reported no attempts to treat himself, stating that he was “just keeping an eye on it and hoping it would go away.”

The patient’s medical history was limited to hypertension, for which he was taking valsartan, and allergies, for which he took fexofenadine. His surgical history included a tonsillectomy and appendectomy during his early teens. He had no known allergies to any medications.

The patient was married and retired after an executive career. He and his wife split their residence between New York and Florida during seasonal changes and were living in Florida at the time. He reported social drinking (“on rare occasions, these days”) and smoking an occasional cigar. He reported that he showers only once or twice weekly because of dry skin.

The following vital signs were recorded: blood pressure, 110/72 mm Hg; heart rate, 68 beats/min; respirations, 15/min; temperature, 97.8°F; and O2 saturation, 99% on room air. He was 73” tall and weighed 197 lb, with a BMI of 26.

The patient was alert and oriented. His physical exam was overall unremarkable, with the exception of an uncircumcised penis with redness and inflammation on the glans penis and no discharge noted. The reddened area was bright and shiny with a moist appearance and well-defined borders. The man denied any risk for sexually transmitted disease (STD) and denied any penile discharge. He also denied fever, chills, or arthritis.

Urinalysis performed in the office was negative for a urinary tract infection or for elevated glucose. A laboratory report from six months earlier was reviewed; all findings were within normal range, including the blood glucose level, with special attention paid for possible underlying cause; and the prostate-specific antigen (PSA) level, obtained for possible prostatitis or prostate cancer.

The differential diagnosis included eczema or psoriasis, Zoon’s balanitis, penile cancer, balanitis xerotica obliterans (lichen sclerosus), candidiasis balanitis, and circinate balanitis (as occurs in patients with Reiter’s disease; see table^1-5). The absence of circumcision and the patient’s report of infrequent bathing raised concern for a hygiene-related etiology; the final diagnosis, made empirically, was candidiasis balanitis. Regarding an underlying cause, the laboratory order included a urine culture, fasting complete blood count, chemistry panel, and PSA level.

The patient was given instructions to wash the affected area twice daily for one week with a lukewarm weak saline solution (1 tablespoon salt/L water),^5,6 gently retracting the foreskin; he was also given a topical antifungal cream⁷ (ketoconazole 2%, although other choices are discussed below), to be applied two to three times daily until his symptoms resolved.⁶ He was advised to return in one week if the condition did not improve or grew worse⁵; referral to dermatology would then be considered. The patient was also advised that in the case of a recurrent episode, dermatology would be consulted. The possibility of circumcision was discussed,⁸ and the patient was given information about the procedure, with referral to a urologist in the area.

Discussion

Balanitis is an inflammation of the glans penis; balanoposthitis involves the foreskin and prepuce.^9-11 Balanitis can occur in men of any age, with etiologies varying with a patient’s age. Typical signs and symptoms include redness and swelling of the glans penis or foreskin, itching and/or pain, urethral discharge, phimosis, swollen lymph nodes, ulceration or plaque appearance, and pain on urination.¹²

In addition to the differential diagnoses mentioned, several additional conditions can be considered in a man with penile lesions. In older men, it is particularly important to investigate such lesions thoroughly, following the patient until the underlying cause is determined and the best treatment choice is selected. Specialists in dermatology and urology can best identify persistent or chronic lesions and make appropriate treatment recommendations, including possible circumcision.

The condition is commonly associated with absence of circumcision, poor hygiene, and phimosis (the inability to retract the foreskin from the glans penis). Accumulation of glandular secretions (smegma) and sloughed epithelial cells under the foreskin can lead to irritation and subsequent infection.

Uncontrolled or poorly controlled diabetes can be implicated in candidiasis infections.¹ Other causes and contributing factors include chemical irritants (eg, soaps, lubricating jelly), edematous conditions (including congestive heart failure, cirrhosis, and nephrosis), drug allergies, morbid obesity, and a number of viruses and other pathogens, including those associated with STDs.¹²

A more detailed laboratory work-up might include the following:

• Serum glucose test (as part of a diabetes screening; in older men, this inflammatory condition can be a presenting sign of diabetes mellitus⁶)

• Culture of discharge, if any is present

• Serology test for STDs

• Wet mount with potassium hydroxide (for Candida albicans infection)

• Ultrasound, in severe cases or when urinary obstruction is suspected.

Additionally, in chronic cases, the patient should be referred to dermatology or urology for biopsy.^5,9 Testing for anaerobes should also be considered for the patient and his sexual partner; if results are positive, treatment with oral metronidazole (400 mg tid for 10 days) is advised.⁶

In this patient’s case, the test that would best support an in-office diagnosis of candidiasis balanitis is a wet mount with potassium hydroxide. This was not performed at the time of the case patient’s visit, however; the diagnosis was empirically determined.

Management, Including Patient Education

Treatment of candidiasis balanitis involves routinely cleaning the penis and foreskin, as the case patient was instructed; use of soap, an irritant, should be avoided until the condition is resolved.^7,10 Appropriate topical antifungal creams include nystatin, ketoconazole, miconazole, clotrimazole, econazole, and terbinafine, applied two to three times daily for at least 10 days; a cream combining an imidazole with 1% hydrocortisone may be effective for patients with significant inflammation.^5,6,8,10,13

The patient should be instructed to:

• Keep the area clean and dry

• Wash twice daily with weak saline solution after removing residual medication and before applying fresh medication

• Wear loose cotton underwear

• Avoid sharing towels or cleaning cloths

• Wash personal items and surfaces, if possible, with disinfectant

• Notify sexual partner(s) that they may need treatment

• Discontinue sexual intercourse until infection is resolved

• Continue treatment for 10 to 14 days, even though relief may occur early

• Follow up with the clinician if no improvement is seen within one week

• Consider circumcision, in case of chronic infection.^1,2,8,12

Conclusion

It is important to diagnose balanitis correctly, as this condition can affect sexual and urinary function, and its effects should not be underestimated in older men. Differentiating between infectious, noninfectious, premalignant, and malignant lesions will lead to appropriate care and allow early diagnosis or prevention of curable malignancies.

A 72-year-old man presented to his primary care provider’s office with complaints of peeling skin on his penis and frequent, burning urination. He said he had first noticed redness on his penis about four days earlier, adding that it was growing worse. He was unsure whether he was truly experiencing frequent urination or just more aware of urinating because of the burning pain. He reported no attempts to treat himself, stating that he was “just keeping an eye on it and hoping it would go away.”

The patient’s medical history was limited to hypertension, for which he was taking valsartan, and allergies, for which he took fexofenadine. His surgical history included a tonsillectomy and appendectomy during his early teens. He had no known allergies to any medications.

The patient was married and retired after an executive career. He and his wife split their residence between New York and Florida during seasonal changes and were living in Florida at the time. He reported social drinking (“on rare occasions, these days”) and smoking an occasional cigar. He reported that he showers only once or twice weekly because of dry skin.

The following vital signs were recorded: blood pressure, 110/72 mm Hg; heart rate, 68 beats/min; respirations, 15/min; temperature, 97.8°F; and O2 saturation, 99% on room air. He was 73” tall and weighed 197 lb, with a BMI of 26.

The patient was alert and oriented. His physical exam was overall unremarkable, with the exception of an uncircumcised penis with redness and inflammation on the glans penis and no discharge noted. The reddened area was bright and shiny with a moist appearance and well-defined borders. The man denied any risk for sexually transmitted disease (STD) and denied any penile discharge. He also denied fever, chills, or arthritis.

Urinalysis performed in the office was negative for a urinary tract infection or for elevated glucose. A laboratory report from six months earlier was reviewed; all findings were within normal range, including the blood glucose level, with special attention paid for possible underlying cause; and the prostate-specific antigen (PSA) level, obtained for possible prostatitis or prostate cancer.

The differential diagnosis included eczema or psoriasis, Zoon’s balanitis, penile cancer, balanitis xerotica obliterans (lichen sclerosus), candidiasis balanitis, and circinate balanitis (as occurs in patients with Reiter’s disease; see table^1-5). The absence of circumcision and the patient’s report of infrequent bathing raised concern for a hygiene-related etiology; the final diagnosis, made empirically, was candidiasis balanitis. Regarding an underlying cause, the laboratory order included a urine culture, fasting complete blood count, chemistry panel, and PSA level.

The patient was given instructions to wash the affected area twice daily for one week with a lukewarm weak saline solution (1 tablespoon salt/L water),^5,6 gently retracting the foreskin; he was also given a topical antifungal cream⁷ (ketoconazole 2%, although other choices are discussed below), to be applied two to three times daily until his symptoms resolved.⁶ He was advised to return in one week if the condition did not improve or grew worse⁵; referral to dermatology would then be considered. The patient was also advised that in the case of a recurrent episode, dermatology would be consulted. The possibility of circumcision was discussed,⁸ and the patient was given information about the procedure, with referral to a urologist in the area.

Discussion

Balanitis is an inflammation of the glans penis; balanoposthitis involves the foreskin and prepuce.^9-11 Balanitis can occur in men of any age, with etiologies varying with a patient’s age. Typical signs and symptoms include redness and swelling of the glans penis or foreskin, itching and/or pain, urethral discharge, phimosis, swollen lymph nodes, ulceration or plaque appearance, and pain on urination.¹²

In addition to the differential diagnoses mentioned, several additional conditions can be considered in a man with penile lesions. In older men, it is particularly important to investigate such lesions thoroughly, following the patient until the underlying cause is determined and the best treatment choice is selected. Specialists in dermatology and urology can best identify persistent or chronic lesions and make appropriate treatment recommendations, including possible circumcision.

The condition is commonly associated with absence of circumcision, poor hygiene, and phimosis (the inability to retract the foreskin from the glans penis). Accumulation of glandular secretions (smegma) and sloughed epithelial cells under the foreskin can lead to irritation and subsequent infection.

Uncontrolled or poorly controlled diabetes can be implicated in candidiasis infections.¹ Other causes and contributing factors include chemical irritants (eg, soaps, lubricating jelly), edematous conditions (including congestive heart failure, cirrhosis, and nephrosis), drug allergies, morbid obesity, and a number of viruses and other pathogens, including those associated with STDs.¹²

A more detailed laboratory work-up might include the following:

• Serum glucose test (as part of a diabetes screening; in older men, this inflammatory condition can be a presenting sign of diabetes mellitus⁶)

• Culture of discharge, if any is present

• Serology test for STDs

• Wet mount with potassium hydroxide (for Candida albicans infection)

• Ultrasound, in severe cases or when urinary obstruction is suspected.

Additionally, in chronic cases, the patient should be referred to dermatology or urology for biopsy.^5,9 Testing for anaerobes should also be considered for the patient and his sexual partner; if results are positive, treatment with oral metronidazole (400 mg tid for 10 days) is advised.⁶

In this patient’s case, the test that would best support an in-office diagnosis of candidiasis balanitis is a wet mount with potassium hydroxide. This was not performed at the time of the case patient’s visit, however; the diagnosis was empirically determined.

Management, Including Patient Education

Treatment of candidiasis balanitis involves routinely cleaning the penis and foreskin, as the case patient was instructed; use of soap, an irritant, should be avoided until the condition is resolved.^7,10 Appropriate topical antifungal creams include nystatin, ketoconazole, miconazole, clotrimazole, econazole, and terbinafine, applied two to three times daily for at least 10 days; a cream combining an imidazole with 1% hydrocortisone may be effective for patients with significant inflammation.^5,6,8,10,13

The patient should be instructed to:

• Keep the area clean and dry

• Wash twice daily with weak saline solution after removing residual medication and before applying fresh medication

• Wear loose cotton underwear

• Avoid sharing towels or cleaning cloths

• Wash personal items and surfaces, if possible, with disinfectant

• Notify sexual partner(s) that they may need treatment

• Discontinue sexual intercourse until infection is resolved

• Continue treatment for 10 to 14 days, even though relief may occur early

• Follow up with the clinician if no improvement is seen within one week

• Consider circumcision, in case of chronic infection.^1,2,8,12

Conclusion

It is important to diagnose balanitis correctly, as this condition can affect sexual and urinary function, and its effects should not be underestimated in older men. Differentiating between infectious, noninfectious, premalignant, and malignant lesions will lead to appropriate care and allow early diagnosis or prevention of curable malignancies.

Q: I frequently counsel patients on family planning, pregnancy expectations, and postpartum concerns. Would you please discuss the specifics of postpartum thyroiditis?

Postpartum thyroiditis (PPT) affects about 5% to 10% of postpartum patients, as evidenced by biochemical thyroid dysfunction. It usually presents during the first three to nine months postpartum.

The condition may present as transient hyperthyroidism, transient hypothyroidism, or hyperthyroidism resolving to transient or permanent hypothyroidism. Only one-quarter to one-third of women experience both the hyperthyroid and hypothyroid phases; one-third of patients will have only a thyrotoxic or hypothyroid phase.

Those who are at risk for or develop PPT have underlying autoimmune thyroid disease (eg, Hashimoto’s thyroiditis). During pregnancy, the maternal immune system is partially suppressed; it rebounds dramatically after delivery, leading to increased risk for autoimmune thyroid disease in patients with thyroid peroxidase antibodies (TPOAb).

Q: How do I know if my patients are at risk for thyroid disease during or following pregnancy?

We need to ascertain who is at risk for PPT so we can appropriately evaluate and screen for the condition. It is important to educate your patients prior to or during pregnancy about the risk, timeline of occurrence, and signs/symptoms of PPT.

If possible, I recommend discussing this with patients in the family-planning stages. It would be helpful to ask the prospective mother about a family history of hyperthyroid or hypothyroid disease (eg, Grave’s disease or Hashimoto’s thyroiditis). It’s also important to inquire about other autoimmune diseases in the patient or in her family.

Other autoimmune conditions that increase the risk for thyroid disease are: systemic lupus erythematosus, rheumatoid arthritis, pernicious anemia, vitiligo, type 1 diabetes, and Addison’s disease. Of note, patients with type 1 diabetes are three times more likely than those without that condition to develop PPT.

Q: Which tests will provide the best information about risk for or presence of PPT? When should I order such tests? 

The thyroid-stimulating hormone (TSH) assay is the most sensitive laboratory test for thyroid function in a patient with a normal pituitary-thyroid axis. Testing for TPOAb is the best available screening tool for postpartum thyroiditis, being widely available, economical, and reproducible. Studies evaluating the utility of TPOAb have demonstrated a sensitivity of 46% to 89%, with a specificity of 91% to 98%. Depending on the timeline of the postpartum presentation, an elevated or low TSH level in conjunction with positive TPOAb is pathognomonic for PPT.

If the prospective or expectant mother has a personal or family history of an autoimmune disease, it would be a good idea to obtain a baseline TSH level and TPOAb. If unobtainable beforehand, a baseline TSH during pregnancy is prudent, since many of the signs and symptoms of hyper/hypothyroidism can be similar to those seen in “normal” pregnancy. A normal TSH in the face of elevated TPOAb increases the patient’s likelihood of developing Hashimoto’s thyroiditis or PPT. The best time to check TPOAb is before pregnancy or after delivery, since these antibodies can decrease or even normalize during pregnancy.

Q: Since PPT can be elusive, how might one clinically evaluate the postpartum patient?

The reasons for missed diagnosis of PPT are twofold. First, it results from women reporting few to no symptoms or simply “writing off” the signs and symptoms, thinking they’re related to the significant emotional/physical demands of caring for the new baby. Second, there is a lack of clinician recognition regarding the risk factors, clinical presentation, and frequency of PPT. Since one-third of the hyperthyroidism of PPT is asymptomatic or unreported by patients, it’s easy to see how clinicians can be uncertain whether postpartum anxiety, insomnia, palpitations, increased heart rate, and fatigue reflect thyrotoxicosis or “new mother demands.” Similarly, fatigue, constipation, impaired concentration/memory, weight gain, and depression can be interpreted as hypothyroidism or the emotional and physical challenges of infant care. Since either hyperthyroid or hypothyroid symptoms can be subtle, PPT goes undiagnosed—and therefore, untreated.

Here is an example to provide a clearer understanding:

PPT can go from hyperthyroid to hypothyroid over a four- to six-month period. I like to refer to this evolving process in its three phases to foster understanding of what is going on not only symptomatically but biochemically as well. The first phase starts with a bout of hyperthyroidism from an increased release of thyroid hormone (T4 and/or T3) as a result of nonpainful/nontender thyroid inflammation.

During this first phase, it’s unfortunate that many new mothers’ symptoms are “written off” as the anxieties associated with being a new mother. If a TSH is not ordered, the woman may feel that the clinician is correct in the assessment and that this is all a natural part of the postpartum period. If her hyperthyroid symptoms worsen, she is unlikely to seek follow-up care for fear of being deemed an “anxious mother,” and as a result, the correct diagnosis is missed. 

After approximately two months, the new mother feels better, as the excess thyroid hormones normalize. This is the second (euthryoid) phase. She may now be convinced that her symptoms of anxiety, agitation, palpitations, and insomnia were from the new experience of motherhood or from the new addition to her existing family. 

After two to three months of feeling well, she begins to experience symptoms of hypothyroidism, which is the third phase of PPT. Her symptoms may include depression, constipation, fatigue, and difficulty concentrating. This is another critical time in which the patient or her clinician may attribute her symptoms to all of the emotional changes and demands of caring for her infant. The clinician may question how the mother has felt over the previous couple of months, and since she has felt well, no thyroid studies are ordered. Again, not questioning the assessment, the mother moves on, only to experience worsening symptoms.

The problem here is that if her hypothyroidism is of a permanent nature, as in the case of autoimmune thyroid disease from Hashimoto’s, she will eventually become more symptomatic but may not return for screening or treatment, thinking this is part of the “normal” postpartum period.

Nearly 20% of PPT patients will remain hypothyroid and require lifelong thyroid hormone replacement. The remaining 80% may develop temporary hypothyroidism, requiring thyroid hormone replacement for up to one year, or the thyroiditis will be mild and resolve without the need for such treatment.

Things to Keep in Mind

Understanding who is at increased risk for PPT should prompt the clinician to check the TSH level and TPOAb before pregnancy, if possible. If the patient is pregnant and has the above stated risk factors for autoimmune thyroiditis, obtaining a baseline TSH level is prudent. In order to obtain a more accurate laboratory evaluation, it would be advisable to wait until after pregnancy to check TPOAb, since the maternal immune system is partially suppressed.

If TPOAb can’t be checked until after delivery, it would make clinical sense to test TSH at the same time (around month 3). In women with positive TPOAb before pregnancy and normal thyroid function throughout pregnancy, TSH should be checked at three and six months postpartum. Clinicians should remain astute and order a TSH any time in the interim if they suspect thyroid dysfunction based on patients’ symptoms. Literature supports annual TSH assays in patients in whom PPT resolved, as they have a markedly increased risk for permanent hypothyroidism.

Suggested Reading

Abalovich M, Amino N, Barbour LA, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007;92(8 suppl):S1-S47.

American Thyroid Association Web site. www.thyroid.org.

Stagno-Green A. Postpartum thyroiditis. J Clin Endocrinol Metab. 2002;87(9):4042-4047.

Q: I frequently counsel patients on family planning, pregnancy expectations, and postpartum concerns. Would you please discuss the specifics of postpartum thyroiditis?

Postpartum thyroiditis (PPT) affects about 5% to 10% of postpartum patients, as evidenced by biochemical thyroid dysfunction. It usually presents during the first three to nine months postpartum.

The condition may present as transient hyperthyroidism, transient hypothyroidism, or hyperthyroidism resolving to transient or permanent hypothyroidism. Only one-quarter to one-third of women experience both the hyperthyroid and hypothyroid phases; one-third of patients will have only a thyrotoxic or hypothyroid phase.

Those who are at risk for or develop PPT have underlying autoimmune thyroid disease (eg, Hashimoto’s thyroiditis). During pregnancy, the maternal immune system is partially suppressed; it rebounds dramatically after delivery, leading to increased risk for autoimmune thyroid disease in patients with thyroid peroxidase antibodies (TPOAb).

Q: How do I know if my patients are at risk for thyroid disease during or following pregnancy?

We need to ascertain who is at risk for PPT so we can appropriately evaluate and screen for the condition. It is important to educate your patients prior to or during pregnancy about the risk, timeline of occurrence, and signs/symptoms of PPT.

If possible, I recommend discussing this with patients in the family-planning stages. It would be helpful to ask the prospective mother about a family history of hyperthyroid or hypothyroid disease (eg, Grave’s disease or Hashimoto’s thyroiditis). It’s also important to inquire about other autoimmune diseases in the patient or in her family.

Other autoimmune conditions that increase the risk for thyroid disease are: systemic lupus erythematosus, rheumatoid arthritis, pernicious anemia, vitiligo, type 1 diabetes, and Addison’s disease. Of note, patients with type 1 diabetes are three times more likely than those without that condition to develop PPT.

Q: Which tests will provide the best information about risk for or presence of PPT? When should I order such tests? 

The thyroid-stimulating hormone (TSH) assay is the most sensitive laboratory test for thyroid function in a patient with a normal pituitary-thyroid axis. Testing for TPOAb is the best available screening tool for postpartum thyroiditis, being widely available, economical, and reproducible. Studies evaluating the utility of TPOAb have demonstrated a sensitivity of 46% to 89%, with a specificity of 91% to 98%. Depending on the timeline of the postpartum presentation, an elevated or low TSH level in conjunction with positive TPOAb is pathognomonic for PPT.

If the prospective or expectant mother has a personal or family history of an autoimmune disease, it would be a good idea to obtain a baseline TSH level and TPOAb. If unobtainable beforehand, a baseline TSH during pregnancy is prudent, since many of the signs and symptoms of hyper/hypothyroidism can be similar to those seen in “normal” pregnancy. A normal TSH in the face of elevated TPOAb increases the patient’s likelihood of developing Hashimoto’s thyroiditis or PPT. The best time to check TPOAb is before pregnancy or after delivery, since these antibodies can decrease or even normalize during pregnancy.

Q: Since PPT can be elusive, how might one clinically evaluate the postpartum patient?

The reasons for missed diagnosis of PPT are twofold. First, it results from women reporting few to no symptoms or simply “writing off” the signs and symptoms, thinking they’re related to the significant emotional/physical demands of caring for the new baby. Second, there is a lack of clinician recognition regarding the risk factors, clinical presentation, and frequency of PPT. Since one-third of the hyperthyroidism of PPT is asymptomatic or unreported by patients, it’s easy to see how clinicians can be uncertain whether postpartum anxiety, insomnia, palpitations, increased heart rate, and fatigue reflect thyrotoxicosis or “new mother demands.” Similarly, fatigue, constipation, impaired concentration/memory, weight gain, and depression can be interpreted as hypothyroidism or the emotional and physical challenges of infant care. Since either hyperthyroid or hypothyroid symptoms can be subtle, PPT goes undiagnosed—and therefore, untreated.

Here is an example to provide a clearer understanding:

PPT can go from hyperthyroid to hypothyroid over a four- to six-month period. I like to refer to this evolving process in its three phases to foster understanding of what is going on not only symptomatically but biochemically as well. The first phase starts with a bout of hyperthyroidism from an increased release of thyroid hormone (T4 and/or T3) as a result of nonpainful/nontender thyroid inflammation.

During this first phase, it’s unfortunate that many new mothers’ symptoms are “written off” as the anxieties associated with being a new mother. If a TSH is not ordered, the woman may feel that the clinician is correct in the assessment and that this is all a natural part of the postpartum period. If her hyperthyroid symptoms worsen, she is unlikely to seek follow-up care for fear of being deemed an “anxious mother,” and as a result, the correct diagnosis is missed. 

After approximately two months, the new mother feels better, as the excess thyroid hormones normalize. This is the second (euthryoid) phase. She may now be convinced that her symptoms of anxiety, agitation, palpitations, and insomnia were from the new experience of motherhood or from the new addition to her existing family. 

After two to three months of feeling well, she begins to experience symptoms of hypothyroidism, which is the third phase of PPT. Her symptoms may include depression, constipation, fatigue, and difficulty concentrating. This is another critical time in which the patient or her clinician may attribute her symptoms to all of the emotional changes and demands of caring for her infant. The clinician may question how the mother has felt over the previous couple of months, and since she has felt well, no thyroid studies are ordered. Again, not questioning the assessment, the mother moves on, only to experience worsening symptoms.

The problem here is that if her hypothyroidism is of a permanent nature, as in the case of autoimmune thyroid disease from Hashimoto’s, she will eventually become more symptomatic but may not return for screening or treatment, thinking this is part of the “normal” postpartum period.

Nearly 20% of PPT patients will remain hypothyroid and require lifelong thyroid hormone replacement. The remaining 80% may develop temporary hypothyroidism, requiring thyroid hormone replacement for up to one year, or the thyroiditis will be mild and resolve without the need for such treatment.

Things to Keep in Mind

Understanding who is at increased risk for PPT should prompt the clinician to check the TSH level and TPOAb before pregnancy, if possible. If the patient is pregnant and has the above stated risk factors for autoimmune thyroiditis, obtaining a baseline TSH level is prudent. In order to obtain a more accurate laboratory evaluation, it would be advisable to wait until after pregnancy to check TPOAb, since the maternal immune system is partially suppressed.

If TPOAb can’t be checked until after delivery, it would make clinical sense to test TSH at the same time (around month 3). In women with positive TPOAb before pregnancy and normal thyroid function throughout pregnancy, TSH should be checked at three and six months postpartum. Clinicians should remain astute and order a TSH any time in the interim if they suspect thyroid dysfunction based on patients’ symptoms. Literature supports annual TSH assays in patients in whom PPT resolved, as they have a markedly increased risk for permanent hypothyroidism.

Suggested Reading

Abalovich M, Amino N, Barbour LA, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007;92(8 suppl):S1-S47.

American Thyroid Association Web site. www.thyroid.org.

Stagno-Green A. Postpartum thyroiditis. J Clin Endocrinol Metab. 2002;87(9):4042-4047.

Q: I frequently counsel patients on family planning, pregnancy expectations, and postpartum concerns. Would you please discuss the specifics of postpartum thyroiditis?

Postpartum thyroiditis (PPT) affects about 5% to 10% of postpartum patients, as evidenced by biochemical thyroid dysfunction. It usually presents during the first three to nine months postpartum.

The condition may present as transient hyperthyroidism, transient hypothyroidism, or hyperthyroidism resolving to transient or permanent hypothyroidism. Only one-quarter to one-third of women experience both the hyperthyroid and hypothyroid phases; one-third of patients will have only a thyrotoxic or hypothyroid phase.

Those who are at risk for or develop PPT have underlying autoimmune thyroid disease (eg, Hashimoto’s thyroiditis). During pregnancy, the maternal immune system is partially suppressed; it rebounds dramatically after delivery, leading to increased risk for autoimmune thyroid disease in patients with thyroid peroxidase antibodies (TPOAb).

Q: How do I know if my patients are at risk for thyroid disease during or following pregnancy?

We need to ascertain who is at risk for PPT so we can appropriately evaluate and screen for the condition. It is important to educate your patients prior to or during pregnancy about the risk, timeline of occurrence, and signs/symptoms of PPT.

If possible, I recommend discussing this with patients in the family-planning stages. It would be helpful to ask the prospective mother about a family history of hyperthyroid or hypothyroid disease (eg, Grave’s disease or Hashimoto’s thyroiditis). It’s also important to inquire about other autoimmune diseases in the patient or in her family.

Other autoimmune conditions that increase the risk for thyroid disease are: systemic lupus erythematosus, rheumatoid arthritis, pernicious anemia, vitiligo, type 1 diabetes, and Addison’s disease. Of note, patients with type 1 diabetes are three times more likely than those without that condition to develop PPT.

Q: Which tests will provide the best information about risk for or presence of PPT? When should I order such tests? 

The thyroid-stimulating hormone (TSH) assay is the most sensitive laboratory test for thyroid function in a patient with a normal pituitary-thyroid axis. Testing for TPOAb is the best available screening tool for postpartum thyroiditis, being widely available, economical, and reproducible. Studies evaluating the utility of TPOAb have demonstrated a sensitivity of 46% to 89%, with a specificity of 91% to 98%. Depending on the timeline of the postpartum presentation, an elevated or low TSH level in conjunction with positive TPOAb is pathognomonic for PPT.

If the prospective or expectant mother has a personal or family history of an autoimmune disease, it would be a good idea to obtain a baseline TSH level and TPOAb. If unobtainable beforehand, a baseline TSH during pregnancy is prudent, since many of the signs and symptoms of hyper/hypothyroidism can be similar to those seen in “normal” pregnancy. A normal TSH in the face of elevated TPOAb increases the patient’s likelihood of developing Hashimoto’s thyroiditis or PPT. The best time to check TPOAb is before pregnancy or after delivery, since these antibodies can decrease or even normalize during pregnancy.

Q: Since PPT can be elusive, how might one clinically evaluate the postpartum patient?

The reasons for missed diagnosis of PPT are twofold. First, it results from women reporting few to no symptoms or simply “writing off” the signs and symptoms, thinking they’re related to the significant emotional/physical demands of caring for the new baby. Second, there is a lack of clinician recognition regarding the risk factors, clinical presentation, and frequency of PPT. Since one-third of the hyperthyroidism of PPT is asymptomatic or unreported by patients, it’s easy to see how clinicians can be uncertain whether postpartum anxiety, insomnia, palpitations, increased heart rate, and fatigue reflect thyrotoxicosis or “new mother demands.” Similarly, fatigue, constipation, impaired concentration/memory, weight gain, and depression can be interpreted as hypothyroidism or the emotional and physical challenges of infant care. Since either hyperthyroid or hypothyroid symptoms can be subtle, PPT goes undiagnosed—and therefore, untreated.

Here is an example to provide a clearer understanding:

PPT can go from hyperthyroid to hypothyroid over a four- to six-month period. I like to refer to this evolving process in its three phases to foster understanding of what is going on not only symptomatically but biochemically as well. The first phase starts with a bout of hyperthyroidism from an increased release of thyroid hormone (T4 and/or T3) as a result of nonpainful/nontender thyroid inflammation.

During this first phase, it’s unfortunate that many new mothers’ symptoms are “written off” as the anxieties associated with being a new mother. If a TSH is not ordered, the woman may feel that the clinician is correct in the assessment and that this is all a natural part of the postpartum period. If her hyperthyroid symptoms worsen, she is unlikely to seek follow-up care for fear of being deemed an “anxious mother,” and as a result, the correct diagnosis is missed. 

After approximately two months, the new mother feels better, as the excess thyroid hormones normalize. This is the second (euthryoid) phase. She may now be convinced that her symptoms of anxiety, agitation, palpitations, and insomnia were from the new experience of motherhood or from the new addition to her existing family. 

After two to three months of feeling well, she begins to experience symptoms of hypothyroidism, which is the third phase of PPT. Her symptoms may include depression, constipation, fatigue, and difficulty concentrating. This is another critical time in which the patient or her clinician may attribute her symptoms to all of the emotional changes and demands of caring for her infant. The clinician may question how the mother has felt over the previous couple of months, and since she has felt well, no thyroid studies are ordered. Again, not questioning the assessment, the mother moves on, only to experience worsening symptoms.

The problem here is that if her hypothyroidism is of a permanent nature, as in the case of autoimmune thyroid disease from Hashimoto’s, she will eventually become more symptomatic but may not return for screening or treatment, thinking this is part of the “normal” postpartum period.

Nearly 20% of PPT patients will remain hypothyroid and require lifelong thyroid hormone replacement. The remaining 80% may develop temporary hypothyroidism, requiring thyroid hormone replacement for up to one year, or the thyroiditis will be mild and resolve without the need for such treatment.

Things to Keep in Mind

Understanding who is at increased risk for PPT should prompt the clinician to check the TSH level and TPOAb before pregnancy, if possible. If the patient is pregnant and has the above stated risk factors for autoimmune thyroiditis, obtaining a baseline TSH level is prudent. In order to obtain a more accurate laboratory evaluation, it would be advisable to wait until after pregnancy to check TPOAb, since the maternal immune system is partially suppressed.

If TPOAb can’t be checked until after delivery, it would make clinical sense to test TSH at the same time (around month 3). In women with positive TPOAb before pregnancy and normal thyroid function throughout pregnancy, TSH should be checked at three and six months postpartum. Clinicians should remain astute and order a TSH any time in the interim if they suspect thyroid dysfunction based on patients’ symptoms. Literature supports annual TSH assays in patients in whom PPT resolved, as they have a markedly increased risk for permanent hypothyroidism.

Suggested Reading

Abalovich M, Amino N, Barbour LA, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007;92(8 suppl):S1-S47.

American Thyroid Association Web site. www.thyroid.org.

Stagno-Green A. Postpartum thyroiditis. J Clin Endocrinol Metab. 2002;87(9):4042-4047.

When a woman has advanced prolapse of the anterior vaginal wall, it is highly likely that she has apical prolapse as well. Consider a study by Rooney and associates that determined that clinically significant vault prolapse is present in most women who have anterior vaginal prolapse of stage II or higher.¹ For that reason, suspension of the vaginal apex should be considered whenever surgical treatment of anterior wall defects is planned.

Sacrocolpopexy involves suspension of the vaginal vault from the anterior longitudinal ligament of the sacrum, using Y-shaped mesh to augment native tissue (FIGURE).² It is an effective, durable treatment for vaginal apical prolapse. With a success rate approaching 93%, this procedure has become the gold standard for repair of vault prolapse. Among its advantages are maximization of vaginal depth and preservation of a normal vaginal axis.

Sacrocolpopexy preserves the vaginal axis

With the vaginal vault suspended from the anterior longitudinal
ligament of the sacrum, the normal vaginal axis is preserved
and vaginal depth is maximized.

Sacrocolpopexy can be performed via the abdominal, laparoscopic, or robotic-assisted approach (TABLE 1). Minimally invasive techniques are attractive because they involve faster recovery than abdominal sacrocolpopexy does. Minimally invasive techniques have also advanced to the point that they are both effective and durable. However, these advantages must be weighed against the effort required to learn the techniques, as well as their higher cost.

TABLE 1

How the 3 approaches to sacrocolpopexy compare

In this article, we highlight:

• a comparison of the laparoscopic and abdominal approaches to sacrocolpopexy
• an investigation of the learning curve associated with robotic-assisted sacrocolpopexy
• a study exploring the durability of robotic-assisted repair
• an estimate of the costs associated with each route of operation.

Laparoscopic vs abdominal sacrocolpopexy—how do they compare?

Paraiso MF, Walters MD, Rackley RR, Melek S, Hugney C. Laparoscopic and abdominal sacral colpopexies: a comparative cohort study. Am J Obstet Gynecol. 2005;192(5):1752–1758.

When surgeons at the Cleveland Clinic performed a retrospective cohort study to compare laparoscopic and abdominal sacrocolpopexy, they found significantly longer operative time with the laparoscopic route, with an average difference of 51 minutes (P < .0001). However, the laparoscopic approach was associated with lower blood loss (although there was no difference between groups in hematocrit on postoperative day 1); shorter hospital stay (average of 1.8 days versus 4 days [P < .001]); and comparable rates of intraoperative and postoperative complications.

Details of the trial

Paraiso and colleagues reviewed the medical charts of 56 consecutive patients who had undergone laparoscopic sacrocolpopexy, comparing them with the charts of 61 consecutive patients who had undergone the procedure using the abdominal approach. The operations had been performed between 1998 and 2003 for treatment of posthysterectomy vaginal prolapse.

The groups underwent similar rates of concurrent procedures. The laparotomy group had a significantly higher number of Burch procedures (P = .007), and the laparoscopic group had a significantly higher rate of adhesiolysis (P = .002).

Among the complications noted— which occurred at comparable rates between groups—were cystotomy, enterotomy, need for transfusion, deep-vein thrombosis, ileus, small bowel obstruction, wound infection, ventral hernia, mesh erosion, and recurrent prolapse. One laparoscopic case was converted to laparotomy because of excessive bleeding during the rectopexy portion of the operation.

Laparoscopy may have taken longer than this trial suggests

This study is one of very few well-designed trials comparing laparoscopic sacrocolpopexy to the historical gold standard of abdominal sacrocolpopexy for vault prolapse.

Twenty-eight percent of laparoscopic procedures in this study used tacking devices in lieu of suturing. Had suturing been performed universally, an even greater difference in surgical time may have been observed.

There may also be differences between groups in the durability of the two types of repair, an outcome not included in this particular study.

How steep is the learning curve for robotic-assisted sacrocolpopexy?

Akl MN, Long JB, Giles DL, et al. Robotic-assisted sacrocolpopexy: technique and learning curve. Surg Endosc. 2009;23(10):2390–2394.

Akl and coworkers reviewed the medical records of all patients who had undergone robotic-assisted sacrocolpopexy at the Mayo Clinics in Arizona and Florida between 2004 and 2007. All operations were performed by the same four urogynecologists, with an average operative time of 197.9 minutes (standard deviation, ± 66.8 minutes). However, after the first 10 cases, the operative time decreased by 64.3 minutes—a decline of 25.4% (P < .01; 95% confidence interval [CI], 16.1–112.4 minutes).

Details of the trial

Researchers collected baseline information on participants’ age, stage of prolapse, and concomitant procedures. They also gathered data on average operative time, estimated blood loss, intraoperative and postoperative complications, conversion to laparotomy, and length of hospitalization.

Of 80 women who had advanced pelvic organ prolapse (stage III/IV) who underwent robotic-assisted sacrocolpopexy, 88% underwent concomitant robotic and vaginal procedures, including robotic supracervical hysterectomy, Burch procedure, paravaginal repair, lysis of adhesions, bilateral salpingooophorectomy, vaginal cystocele or rectocele repair, and placement of a midurethral sling.

Estimated blood loss for the robotic-assisted approach ranged from 25 mL to 300 mL, with a mean loss of 96.8 mL. Average length of hospitalization was 2.6 days. Four cases (5%) were converted to laparotomy because of limited exposure and one intraoperative bladder injury. Other intraoperative complications included small-bowel injury during trocar placement and one ureteral injury. Postoperative complications included one case of ileus and five (6%) vaginal mesh erosions. Three patients developed recurrent prolapse and underwent subsequent correction.

Learning curve could have been measured more precisely

The authors did not specifically measure the learning curve for robotic-assisted sacrocolpopexy, as they took into account the concomitant procedures. For this reason, the decrease in operative time observed after 10 cases may not accurately reflect an improvement in the performance of sacrocolpopexy.

Akl and colleagues consider this detail to be a strength of the study because most women who undergo prolapse surgery have concomitant procedures. However, recording the length of time it took to perform the sacrocolpopexy portion of the procedure would have been more accurate.

The average length of stay approached that of the abdominal route. Length of stay may decline as a surgeon gains experience with the robotic-assisted approach.

Does robotic-assisted sacrocolpopexy provide durable support?

Elliott DS, Krambeck AE, Chow GK. Long-term results of robotic assisted laparoscopic sacrocolpopexy for the treatment of high grade vaginal vault prolapse. J Urol. 2006;176(2):655–659.

Among the few recent series reporting long-term outcomes after robotic-assisted sacrocolpopexy is this observational study from the Mayo Clinic. It involved 30 women who underwent the operation for the treatment of Baden Walker grade 4/4 posthysterectomy vaginal vault prolapse. The authors concluded that advanced prolapse can be treated with robotic-assisted sacrocolpopexy with long-term success and minimal complications.

Details of the trial

Of 30 women in this trial, 52% underwent an anti-incontinence procedure at the time of sacrocolpopexy. Women who had multiple vaginal defects or a history of abdominal surgery were excluded from the study.

Average operative time was 3.1 hours (range, 2.15–4.75 hours) in the early phase of development of operative technique (described in the manuscript) but diminished over time to an average of 2.5 hours.

Twenty-nine patients were discharged from the hospital after an overnight stay. Very few immediate postoperative complications were observed. Two patients experienced mild port-site infections that required outpatient treatment, and one patient had persistent vaginal bleeding from the incision made during the anti-incontinence procedure.

Most patients were followed for at least 1 year

The mean follow-up in this study was 24 months (range, 16–39 months). During this period, 21 women were followed for a full year. Long-term observation revealed that the repair of vault prolapse remained successful in 19 of these women.

One patient experienced recurrent prolapse 7 months after surgery. Another developed a rectocele 9 months after sacrocolpopexy. Vaginal mesh erosions occurred in two patients within 6 months after the procedure; both patients were treated with outpatient resection of the exposed mesh, with no recurrence of the prolapse.

Although a larger sample size and longer follow-up would be ideal, this study demonstrates a low rate of recurrent prolapse 1 year after the procedure.

How much do laparoscopic, abdominal, and robotic-assisted sacrocolpopexy cost?

Judd JP, Siddiqui NY, Barnett JC, et al. Cost-minimization analysis of robotic-assisted, laparoscopic, and abdominal sacrocolpopexy. J Minim Invasive Gynecol. 2010;17: 493–499.

This cost-minimization analysis concluded that robotic-assisted sacrocolpopexy incurs the highest hospital charges but is reimbursed by Medicare at a rate similar to reimbursement for the abdominal and laparoscopic routes (TABLE 2).

TABLE 2

Cost of sacrocolpopexy is significant—especially using the robotic approach

The analysis accounted for realistic practices, such as the inclusion of concurrent hysterectomy and other procedures.

Details of the trial

Surgeons from Duke University developed a decision-analysis model in which a hypothetical group of women with advanced vaginal prolapse could choose between one of the three routes of sacrocolpopexy: abdominal, laparoscopic, or robotic-assisted. Researchers postulated two different scenarios:

• the hospital had ownership of a robotic system
• the hospital invested in the initial purchase and maintenance of such a system.

Researchers reviewed the literature to formulate their estimates of operative time, rate of conversion to laparotomy, rate of transfusion, and length of hospital stay. In addition, the costs of initial anesthesia setup, professional fees, per-minute intraoperative fees, and postanesthesia care were applied to each approach. Operating room costs per minute and the cost of disposable items such as drapes, gowns, gloves, and single-use instruments were added. For the robotic approach, the costs of reusable instruments were distributed across 10 operations. Reusable instruments for laparoscopic and abdominal surgery were assumed to incur no additional investment. Last, postoperative care—including laboratory tests, pharmacy usage, and the need for a hospital room—were individualized for each route of surgery and applied to the cost.

Costs were estimated in 2008 US dollars, based on procedure costs incurred at Duke University Medical Center.

Physician reimbursement data were obtained from Medicare reimbursement rates for anesthesia and from surgeon Current Procedural Terminology (CPT) codes specific to each procedure.

Quality-of-life assessments were not measured. Nor was the cost to society of the postoperative loss of productivity and wages for each surgical route. Had these losses been recognized, the authors observed, the cost of robotic surgery may have been lower.

The cost of robotic surgery was equivalent to the cost of laparoscopy in only two instances:

• when the operative time of robotic surgery was reduced to 149 minutes
• when the cost of robotic disposable items was less than $2,132 (reduced from a baseline cost of $3,293).

We want to hear from you! Tell us what you think.

When a woman has advanced prolapse of the anterior vaginal wall, it is highly likely that she has apical prolapse as well. Consider a study by Rooney and associates that determined that clinically significant vault prolapse is present in most women who have anterior vaginal prolapse of stage II or higher.¹ For that reason, suspension of the vaginal apex should be considered whenever surgical treatment of anterior wall defects is planned.

Sacrocolpopexy involves suspension of the vaginal vault from the anterior longitudinal ligament of the sacrum, using Y-shaped mesh to augment native tissue (FIGURE).² It is an effective, durable treatment for vaginal apical prolapse. With a success rate approaching 93%, this procedure has become the gold standard for repair of vault prolapse. Among its advantages are maximization of vaginal depth and preservation of a normal vaginal axis.

Sacrocolpopexy preserves the vaginal axis

With the vaginal vault suspended from the anterior longitudinal
ligament of the sacrum, the normal vaginal axis is preserved
and vaginal depth is maximized.

Sacrocolpopexy can be performed via the abdominal, laparoscopic, or robotic-assisted approach (TABLE 1). Minimally invasive techniques are attractive because they involve faster recovery than abdominal sacrocolpopexy does. Minimally invasive techniques have also advanced to the point that they are both effective and durable. However, these advantages must be weighed against the effort required to learn the techniques, as well as their higher cost.

TABLE 1

How the 3 approaches to sacrocolpopexy compare

In this article, we highlight:

• a comparison of the laparoscopic and abdominal approaches to sacrocolpopexy
• an investigation of the learning curve associated with robotic-assisted sacrocolpopexy
• a study exploring the durability of robotic-assisted repair
• an estimate of the costs associated with each route of operation.

Laparoscopic vs abdominal sacrocolpopexy—how do they compare?

Paraiso MF, Walters MD, Rackley RR, Melek S, Hugney C. Laparoscopic and abdominal sacral colpopexies: a comparative cohort study. Am J Obstet Gynecol. 2005;192(5):1752–1758.

When surgeons at the Cleveland Clinic performed a retrospective cohort study to compare laparoscopic and abdominal sacrocolpopexy, they found significantly longer operative time with the laparoscopic route, with an average difference of 51 minutes (P < .0001). However, the laparoscopic approach was associated with lower blood loss (although there was no difference between groups in hematocrit on postoperative day 1); shorter hospital stay (average of 1.8 days versus 4 days [P < .001]); and comparable rates of intraoperative and postoperative complications.

Details of the trial

Paraiso and colleagues reviewed the medical charts of 56 consecutive patients who had undergone laparoscopic sacrocolpopexy, comparing them with the charts of 61 consecutive patients who had undergone the procedure using the abdominal approach. The operations had been performed between 1998 and 2003 for treatment of posthysterectomy vaginal prolapse.

The groups underwent similar rates of concurrent procedures. The laparotomy group had a significantly higher number of Burch procedures (P = .007), and the laparoscopic group had a significantly higher rate of adhesiolysis (P = .002).

Among the complications noted— which occurred at comparable rates between groups—were cystotomy, enterotomy, need for transfusion, deep-vein thrombosis, ileus, small bowel obstruction, wound infection, ventral hernia, mesh erosion, and recurrent prolapse. One laparoscopic case was converted to laparotomy because of excessive bleeding during the rectopexy portion of the operation.

Laparoscopy may have taken longer than this trial suggests

This study is one of very few well-designed trials comparing laparoscopic sacrocolpopexy to the historical gold standard of abdominal sacrocolpopexy for vault prolapse.

Twenty-eight percent of laparoscopic procedures in this study used tacking devices in lieu of suturing. Had suturing been performed universally, an even greater difference in surgical time may have been observed.

There may also be differences between groups in the durability of the two types of repair, an outcome not included in this particular study.

How steep is the learning curve for robotic-assisted sacrocolpopexy?

Akl MN, Long JB, Giles DL, et al. Robotic-assisted sacrocolpopexy: technique and learning curve. Surg Endosc. 2009;23(10):2390–2394.

Akl and coworkers reviewed the medical records of all patients who had undergone robotic-assisted sacrocolpopexy at the Mayo Clinics in Arizona and Florida between 2004 and 2007. All operations were performed by the same four urogynecologists, with an average operative time of 197.9 minutes (standard deviation, ± 66.8 minutes). However, after the first 10 cases, the operative time decreased by 64.3 minutes—a decline of 25.4% (P < .01; 95% confidence interval [CI], 16.1–112.4 minutes).

Details of the trial

Researchers collected baseline information on participants’ age, stage of prolapse, and concomitant procedures. They also gathered data on average operative time, estimated blood loss, intraoperative and postoperative complications, conversion to laparotomy, and length of hospitalization.

Of 80 women who had advanced pelvic organ prolapse (stage III/IV) who underwent robotic-assisted sacrocolpopexy, 88% underwent concomitant robotic and vaginal procedures, including robotic supracervical hysterectomy, Burch procedure, paravaginal repair, lysis of adhesions, bilateral salpingooophorectomy, vaginal cystocele or rectocele repair, and placement of a midurethral sling.

Estimated blood loss for the robotic-assisted approach ranged from 25 mL to 300 mL, with a mean loss of 96.8 mL. Average length of hospitalization was 2.6 days. Four cases (5%) were converted to laparotomy because of limited exposure and one intraoperative bladder injury. Other intraoperative complications included small-bowel injury during trocar placement and one ureteral injury. Postoperative complications included one case of ileus and five (6%) vaginal mesh erosions. Three patients developed recurrent prolapse and underwent subsequent correction.

Learning curve could have been measured more precisely

The authors did not specifically measure the learning curve for robotic-assisted sacrocolpopexy, as they took into account the concomitant procedures. For this reason, the decrease in operative time observed after 10 cases may not accurately reflect an improvement in the performance of sacrocolpopexy.

Akl and colleagues consider this detail to be a strength of the study because most women who undergo prolapse surgery have concomitant procedures. However, recording the length of time it took to perform the sacrocolpopexy portion of the procedure would have been more accurate.

The average length of stay approached that of the abdominal route. Length of stay may decline as a surgeon gains experience with the robotic-assisted approach.

Does robotic-assisted sacrocolpopexy provide durable support?

Elliott DS, Krambeck AE, Chow GK. Long-term results of robotic assisted laparoscopic sacrocolpopexy for the treatment of high grade vaginal vault prolapse. J Urol. 2006;176(2):655–659.

Among the few recent series reporting long-term outcomes after robotic-assisted sacrocolpopexy is this observational study from the Mayo Clinic. It involved 30 women who underwent the operation for the treatment of Baden Walker grade 4/4 posthysterectomy vaginal vault prolapse. The authors concluded that advanced prolapse can be treated with robotic-assisted sacrocolpopexy with long-term success and minimal complications.

Details of the trial

Of 30 women in this trial, 52% underwent an anti-incontinence procedure at the time of sacrocolpopexy. Women who had multiple vaginal defects or a history of abdominal surgery were excluded from the study.

Average operative time was 3.1 hours (range, 2.15–4.75 hours) in the early phase of development of operative technique (described in the manuscript) but diminished over time to an average of 2.5 hours.

Twenty-nine patients were discharged from the hospital after an overnight stay. Very few immediate postoperative complications were observed. Two patients experienced mild port-site infections that required outpatient treatment, and one patient had persistent vaginal bleeding from the incision made during the anti-incontinence procedure.

Most patients were followed for at least 1 year

The mean follow-up in this study was 24 months (range, 16–39 months). During this period, 21 women were followed for a full year. Long-term observation revealed that the repair of vault prolapse remained successful in 19 of these women.

One patient experienced recurrent prolapse 7 months after surgery. Another developed a rectocele 9 months after sacrocolpopexy. Vaginal mesh erosions occurred in two patients within 6 months after the procedure; both patients were treated with outpatient resection of the exposed mesh, with no recurrence of the prolapse.

Although a larger sample size and longer follow-up would be ideal, this study demonstrates a low rate of recurrent prolapse 1 year after the procedure.

How much do laparoscopic, abdominal, and robotic-assisted sacrocolpopexy cost?

Judd JP, Siddiqui NY, Barnett JC, et al. Cost-minimization analysis of robotic-assisted, laparoscopic, and abdominal sacrocolpopexy. J Minim Invasive Gynecol. 2010;17: 493–499.

This cost-minimization analysis concluded that robotic-assisted sacrocolpopexy incurs the highest hospital charges but is reimbursed by Medicare at a rate similar to reimbursement for the abdominal and laparoscopic routes (TABLE 2).

TABLE 2

Cost of sacrocolpopexy is significant—especially using the robotic approach

The analysis accounted for realistic practices, such as the inclusion of concurrent hysterectomy and other procedures.

Details of the trial

Surgeons from Duke University developed a decision-analysis model in which a hypothetical group of women with advanced vaginal prolapse could choose between one of the three routes of sacrocolpopexy: abdominal, laparoscopic, or robotic-assisted. Researchers postulated two different scenarios:

• the hospital had ownership of a robotic system
• the hospital invested in the initial purchase and maintenance of such a system.

Researchers reviewed the literature to formulate their estimates of operative time, rate of conversion to laparotomy, rate of transfusion, and length of hospital stay. In addition, the costs of initial anesthesia setup, professional fees, per-minute intraoperative fees, and postanesthesia care were applied to each approach. Operating room costs per minute and the cost of disposable items such as drapes, gowns, gloves, and single-use instruments were added. For the robotic approach, the costs of reusable instruments were distributed across 10 operations. Reusable instruments for laparoscopic and abdominal surgery were assumed to incur no additional investment. Last, postoperative care—including laboratory tests, pharmacy usage, and the need for a hospital room—were individualized for each route of surgery and applied to the cost.

Costs were estimated in 2008 US dollars, based on procedure costs incurred at Duke University Medical Center.

Physician reimbursement data were obtained from Medicare reimbursement rates for anesthesia and from surgeon Current Procedural Terminology (CPT) codes specific to each procedure.

Quality-of-life assessments were not measured. Nor was the cost to society of the postoperative loss of productivity and wages for each surgical route. Had these losses been recognized, the authors observed, the cost of robotic surgery may have been lower.

The cost of robotic surgery was equivalent to the cost of laparoscopy in only two instances:

• when the operative time of robotic surgery was reduced to 149 minutes
• when the cost of robotic disposable items was less than $2,132 (reduced from a baseline cost of $3,293).

We want to hear from you! Tell us what you think.

When a woman has advanced prolapse of the anterior vaginal wall, it is highly likely that she has apical prolapse as well. Consider a study by Rooney and associates that determined that clinically significant vault prolapse is present in most women who have anterior vaginal prolapse of stage II or higher.¹ For that reason, suspension of the vaginal apex should be considered whenever surgical treatment of anterior wall defects is planned.

Sacrocolpopexy involves suspension of the vaginal vault from the anterior longitudinal ligament of the sacrum, using Y-shaped mesh to augment native tissue (FIGURE).² It is an effective, durable treatment for vaginal apical prolapse. With a success rate approaching 93%, this procedure has become the gold standard for repair of vault prolapse. Among its advantages are maximization of vaginal depth and preservation of a normal vaginal axis.

Sacrocolpopexy preserves the vaginal axis

With the vaginal vault suspended from the anterior longitudinal
ligament of the sacrum, the normal vaginal axis is preserved
and vaginal depth is maximized.

Sacrocolpopexy can be performed via the abdominal, laparoscopic, or robotic-assisted approach (TABLE 1). Minimally invasive techniques are attractive because they involve faster recovery than abdominal sacrocolpopexy does. Minimally invasive techniques have also advanced to the point that they are both effective and durable. However, these advantages must be weighed against the effort required to learn the techniques, as well as their higher cost.

TABLE 1

How the 3 approaches to sacrocolpopexy compare

In this article, we highlight:

• a comparison of the laparoscopic and abdominal approaches to sacrocolpopexy
• an investigation of the learning curve associated with robotic-assisted sacrocolpopexy
• a study exploring the durability of robotic-assisted repair
• an estimate of the costs associated with each route of operation.

Laparoscopic vs abdominal sacrocolpopexy—how do they compare?

Paraiso MF, Walters MD, Rackley RR, Melek S, Hugney C. Laparoscopic and abdominal sacral colpopexies: a comparative cohort study. Am J Obstet Gynecol. 2005;192(5):1752–1758.

When surgeons at the Cleveland Clinic performed a retrospective cohort study to compare laparoscopic and abdominal sacrocolpopexy, they found significantly longer operative time with the laparoscopic route, with an average difference of 51 minutes (P < .0001). However, the laparoscopic approach was associated with lower blood loss (although there was no difference between groups in hematocrit on postoperative day 1); shorter hospital stay (average of 1.8 days versus 4 days [P < .001]); and comparable rates of intraoperative and postoperative complications.

Details of the trial

Paraiso and colleagues reviewed the medical charts of 56 consecutive patients who had undergone laparoscopic sacrocolpopexy, comparing them with the charts of 61 consecutive patients who had undergone the procedure using the abdominal approach. The operations had been performed between 1998 and 2003 for treatment of posthysterectomy vaginal prolapse.

The groups underwent similar rates of concurrent procedures. The laparotomy group had a significantly higher number of Burch procedures (P = .007), and the laparoscopic group had a significantly higher rate of adhesiolysis (P = .002).

Among the complications noted— which occurred at comparable rates between groups—were cystotomy, enterotomy, need for transfusion, deep-vein thrombosis, ileus, small bowel obstruction, wound infection, ventral hernia, mesh erosion, and recurrent prolapse. One laparoscopic case was converted to laparotomy because of excessive bleeding during the rectopexy portion of the operation.

Laparoscopy may have taken longer than this trial suggests

This study is one of very few well-designed trials comparing laparoscopic sacrocolpopexy to the historical gold standard of abdominal sacrocolpopexy for vault prolapse.

Twenty-eight percent of laparoscopic procedures in this study used tacking devices in lieu of suturing. Had suturing been performed universally, an even greater difference in surgical time may have been observed.

There may also be differences between groups in the durability of the two types of repair, an outcome not included in this particular study.

How steep is the learning curve for robotic-assisted sacrocolpopexy?

Akl MN, Long JB, Giles DL, et al. Robotic-assisted sacrocolpopexy: technique and learning curve. Surg Endosc. 2009;23(10):2390–2394.

Akl and coworkers reviewed the medical records of all patients who had undergone robotic-assisted sacrocolpopexy at the Mayo Clinics in Arizona and Florida between 2004 and 2007. All operations were performed by the same four urogynecologists, with an average operative time of 197.9 minutes (standard deviation, ± 66.8 minutes). However, after the first 10 cases, the operative time decreased by 64.3 minutes—a decline of 25.4% (P < .01; 95% confidence interval [CI], 16.1–112.4 minutes).

Details of the trial

Researchers collected baseline information on participants’ age, stage of prolapse, and concomitant procedures. They also gathered data on average operative time, estimated blood loss, intraoperative and postoperative complications, conversion to laparotomy, and length of hospitalization.

Of 80 women who had advanced pelvic organ prolapse (stage III/IV) who underwent robotic-assisted sacrocolpopexy, 88% underwent concomitant robotic and vaginal procedures, including robotic supracervical hysterectomy, Burch procedure, paravaginal repair, lysis of adhesions, bilateral salpingooophorectomy, vaginal cystocele or rectocele repair, and placement of a midurethral sling.

Estimated blood loss for the robotic-assisted approach ranged from 25 mL to 300 mL, with a mean loss of 96.8 mL. Average length of hospitalization was 2.6 days. Four cases (5%) were converted to laparotomy because of limited exposure and one intraoperative bladder injury. Other intraoperative complications included small-bowel injury during trocar placement and one ureteral injury. Postoperative complications included one case of ileus and five (6%) vaginal mesh erosions. Three patients developed recurrent prolapse and underwent subsequent correction.

Learning curve could have been measured more precisely

The authors did not specifically measure the learning curve for robotic-assisted sacrocolpopexy, as they took into account the concomitant procedures. For this reason, the decrease in operative time observed after 10 cases may not accurately reflect an improvement in the performance of sacrocolpopexy.

Akl and colleagues consider this detail to be a strength of the study because most women who undergo prolapse surgery have concomitant procedures. However, recording the length of time it took to perform the sacrocolpopexy portion of the procedure would have been more accurate.

The average length of stay approached that of the abdominal route. Length of stay may decline as a surgeon gains experience with the robotic-assisted approach.

Does robotic-assisted sacrocolpopexy provide durable support?

Elliott DS, Krambeck AE, Chow GK. Long-term results of robotic assisted laparoscopic sacrocolpopexy for the treatment of high grade vaginal vault prolapse. J Urol. 2006;176(2):655–659.

Among the few recent series reporting long-term outcomes after robotic-assisted sacrocolpopexy is this observational study from the Mayo Clinic. It involved 30 women who underwent the operation for the treatment of Baden Walker grade 4/4 posthysterectomy vaginal vault prolapse. The authors concluded that advanced prolapse can be treated with robotic-assisted sacrocolpopexy with long-term success and minimal complications.

Details of the trial

Of 30 women in this trial, 52% underwent an anti-incontinence procedure at the time of sacrocolpopexy. Women who had multiple vaginal defects or a history of abdominal surgery were excluded from the study.

Average operative time was 3.1 hours (range, 2.15–4.75 hours) in the early phase of development of operative technique (described in the manuscript) but diminished over time to an average of 2.5 hours.

Twenty-nine patients were discharged from the hospital after an overnight stay. Very few immediate postoperative complications were observed. Two patients experienced mild port-site infections that required outpatient treatment, and one patient had persistent vaginal bleeding from the incision made during the anti-incontinence procedure.

Most patients were followed for at least 1 year

The mean follow-up in this study was 24 months (range, 16–39 months). During this period, 21 women were followed for a full year. Long-term observation revealed that the repair of vault prolapse remained successful in 19 of these women.

One patient experienced recurrent prolapse 7 months after surgery. Another developed a rectocele 9 months after sacrocolpopexy. Vaginal mesh erosions occurred in two patients within 6 months after the procedure; both patients were treated with outpatient resection of the exposed mesh, with no recurrence of the prolapse.

Although a larger sample size and longer follow-up would be ideal, this study demonstrates a low rate of recurrent prolapse 1 year after the procedure.

How much do laparoscopic, abdominal, and robotic-assisted sacrocolpopexy cost?

Judd JP, Siddiqui NY, Barnett JC, et al. Cost-minimization analysis of robotic-assisted, laparoscopic, and abdominal sacrocolpopexy. J Minim Invasive Gynecol. 2010;17: 493–499.

This cost-minimization analysis concluded that robotic-assisted sacrocolpopexy incurs the highest hospital charges but is reimbursed by Medicare at a rate similar to reimbursement for the abdominal and laparoscopic routes (TABLE 2).

TABLE 2

Cost of sacrocolpopexy is significant—especially using the robotic approach

The analysis accounted for realistic practices, such as the inclusion of concurrent hysterectomy and other procedures.

Details of the trial

Surgeons from Duke University developed a decision-analysis model in which a hypothetical group of women with advanced vaginal prolapse could choose between one of the three routes of sacrocolpopexy: abdominal, laparoscopic, or robotic-assisted. Researchers postulated two different scenarios:

• the hospital had ownership of a robotic system
• the hospital invested in the initial purchase and maintenance of such a system.

Researchers reviewed the literature to formulate their estimates of operative time, rate of conversion to laparotomy, rate of transfusion, and length of hospital stay. In addition, the costs of initial anesthesia setup, professional fees, per-minute intraoperative fees, and postanesthesia care were applied to each approach. Operating room costs per minute and the cost of disposable items such as drapes, gowns, gloves, and single-use instruments were added. For the robotic approach, the costs of reusable instruments were distributed across 10 operations. Reusable instruments for laparoscopic and abdominal surgery were assumed to incur no additional investment. Last, postoperative care—including laboratory tests, pharmacy usage, and the need for a hospital room—were individualized for each route of surgery and applied to the cost.

Costs were estimated in 2008 US dollars, based on procedure costs incurred at Duke University Medical Center.

Physician reimbursement data were obtained from Medicare reimbursement rates for anesthesia and from surgeon Current Procedural Terminology (CPT) codes specific to each procedure.

Quality-of-life assessments were not measured. Nor was the cost to society of the postoperative loss of productivity and wages for each surgical route. Had these losses been recognized, the authors observed, the cost of robotic surgery may have been lower.

The cost of robotic surgery was equivalent to the cost of laparoscopy in only two instances:

• when the operative time of robotic surgery was reduced to 149 minutes
• when the cost of robotic disposable items was less than $2,132 (reduced from a baseline cost of $3,293).

We want to hear from you! Tell us what you think.

Low-dose doxepin—3 mg and 6 mg—has demonstrated efficacy for insomnia characterized by frequent or early-morning awakenings and an inability to return to sleep (Table 1).¹ FDA-approved in March 2010, doxepin (3 mg and 6 mg) is only the second insomnia medication not designated as a controlled substance and thus may be of special value in patients with a history of substance abuse.

Table 1

Doxepin: Fast facts

Clinical implications

Ramelteon, the other hypnotic that is not a controlled substance, is indicated for sleep initiation insomnia (ie, inability to fall asleep). In contrast, low-dose doxepin is for patients with sleep maintenance insomnia, which is waking up frequently or early in the morning and not falling back asleep.^1,2 A tricyclic antidepressant first approved in 1969, doxepin has long been available in larger doses (10-, 25-, 50-, 75-, 100-, and 150-mg capsules) to treat depression and anxiety and as a topical preparation (5% cream) for pruritus, but not in dosages <10 mg. An inexpensive generic doxepin oral solution (10 mg/ml) is available and can be titrated to smaller dosages by a dropper. Liquid doxepin costs 10 to 20 cents per dose. A pharmacist can provide a dropper, and patients should mix the medication in 4 ounces of water, milk, or juice; 0.3 ml of liquid doxepin contains 3 mg of active ingredient and 0.6 ml of solution contains 6 mg of doxepin. These other dosage forms of doxepin, however, are not FDA-approved for insomnia. (The retail price of low-dose doxepin was not available when this article went to press.)

How it works

Doxepin’s mechanism of action for treating depression and insomnia remains unknown. The antidepressant effect of doxepin is thought to result from inhibition of serotonin and norepinephrine reuptake at the synaptic cleft. Animal studies have shown anticholinergic and antihistaminergic activity with doxepin.² Doxepin is a potent histamine antagonist—predominantly at the H1 receptor—and its binding potency to the H1 receptor is approximately 100-times higher than its binding potency for monoamine transporters (serotonin and norepinephrine).^2,3 Brain histamine is believed to be 1 of the key elements in maintaining wakefulness, and the activation of the H1 receptor is thought to play an important role in mediating arousal. Blockade of the H1 receptor by doxepin likely plays a role in reducing wakefulness. Typically, therapeutic doses of antidepressants with anti-histaminergic properties, such as doxepin at antidepressant doses, amitriptyline, or desipramine, do not selectively block H1 receptors, but act at cholinergic, serotonergic, adrenergic, histaminergic, and muscarinic receptors, which can cause adverse effects.³ However, low doses of doxepin (1, 3, and 6 mg) can achieve selective H1 blockade.^4,5 Patients taking >25 mg/d of doxepin may report clinically significant anticholinergic effects.

Pharmacokinetics

When doxepin, 6 mg, was administered to healthy, fasting patients, time to maximum concentration (Tmax) was 3.5 hours. Peak plasma concentration (Cmax) increased in a dose-related fashion when doxepin was increased from 3 mg to 6 mg. Doxepin, 6 mg, taken with a high-fat meal resulted in area under the curve increase of 41%, Cmax increase of 15%, and almost 3-hour delay in Tmax. Therefore, to prevent a delay in onset of action and to minimize the likelihood of daytime sedation, doxepin should not be taken within 3 hours of a meal.^1-3

Doxepin is metabolized primarily by the liver’s cytochrome P450 (CYP) 2C19 and CYP2D6 enzymes; CYP1A2 and CYP2D6 are involved to a lesser extent. If doxepin is coadministered with drugs that inhibit these isoenzymes, such as fluoxetine and paroxetine, doxepin blood levels may increase. Doxepin does not seem to induce CYP isoenzymes. This medication is metabolized by demethylation and oxidation; the primary metabolite is nordoxepin (N-desmethyldoxepin), which later undergoes glucuronide conjugation. The half-life is 15 hours for doxepin and 31 hours for nordoxepin. Doxepin is excreted in urine primarily as glucuronide conjugate.^1-3

Coadministration with cimetidine, an inhibitor of CYP isoenzymes, could double the doxepin plasma concentration; therefore, patients taking cimetidine should not exceed 3 mg/d of doxepin.

Efficacy

Doxepin reduced insomnia symptoms in 3 pilot studies at doses of 10, 25, and 50 mg, and in 2 phase III randomized, double-blind, placebo-controlled clinical trials using 1, 3, and 6 mg (Table 2).^4,5 Clinical studies lasted up to 3 months.^1-3,6-8

In the first phase III trial, 67 patients, age 18 to 64 with chronic primary insomnia, were randomly assigned to placebo or 1 mg, 3 mg, or 6 mg of doxepin for 2 nights. All patients received all treatments, and each treatment was followed by 8 hours of polysomnography (PSG) evaluation in a sleep laboratory.⁴ In this study, patients taking doxepin at all doses achieved improvement in objective (PSG-defined) and subjective (patient-reported) measures of sleep duration and sleep maintenance. Wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE) improved with all doxepin doses, and wake time during sleep (WTDS)—which was the primary study endpoint—decreased with 3 mg and 6 mg doses, but not with 1 mg or placebo. In addition, PSG indicators of early-morning awakenings (terminal insomnia) were reduced, as shown by an increase in SE during the final third of the night and the 7^th and 8^th hours of sleep (1, 3, and 6 mg doses) and a reduction in wake time after sleep (WTAS) during the final third of the night (6 mg only). The effects on sleep duration and maintenance were more robust with 3 mg and 6 mg doses. Improved sleep onset was seen only with the 6 mg dose. Next-day alertness was assessed using the Visual Analogue Scale (VAS) for sleepiness, and the Digit-Symbol Substitution Test (DSST) and the Symbol-Copying Task (SCT) for psychomotor function. No statistically significant differences were found among placebo and any of the doxepin doses on the VAS, DSST, or SCT.

Doxepin was well tolerated. Reported adverse events were mild or moderate. Headaches and somnolence were reported by >2% of patients. The incidence of adverse events, including next-day sedation, was similar to that of placebo. Additionally, there were no spontaneous reports of anticholinergic side effects, which are associated with higher doxepin doses.⁴

The second phase III trial examined safety and efficacy of 1, 3, and 6 mg doxepin in patients age ≥65.⁵ Seventy-six adults with primary insomnia were randomly assigned to receive placebo or doxepin for 2 nights; all patients received all treatments, and each treatment was followed by an 8-hour PSG. Patients taking any doxepin dose achieved objective and subjective improvement in sleep duration and sleep maintenance, which lasted into the final hours of the night. WTDS (primary study endpoint), WASO, TST, and overall SE improved at all doxepin doses compared with placebo, and WTAS and SE at hours 7 and 8 improved at doxepin doses of 3 mg and 6 mg compared with placebo. These findings suggest that doxepin, 3 mg and 6 mg, can help older insomnia patients with early morning awakenings.

In this study, no statistically significant differences were found among placebo and any doxepin doses on VAS, DSST, or SCT or next-day residual sedation. The incidence of side effects was low and similar to that of placebo. Adverse events were mild or moderate; 1 incident of chest pain was reported, but it was determined not to be of cardiac origin and not related to study drug. There were no spontaneous reports of anticholinergic side effects associated with higher doses of doxepin. There were no reports of memory impairment.⁵

Table 2

Evidence of effectiveness of doxepin for insomnia

Tolerability

Clinical studies that evaluated the safety of doxepin lasted up to 3 months. Somnolence/sedation, nausea, and upper respiratory tract infection were reported by >2% of patients taking doxepin and were more common than in patients treated with placebo.¹ All reported adverse events were mild to moderate.

Doxepin appears to be better tolerated at hypnotic doses (3 mg and 6 mg) than at antidepressant doses (50 to 300 mg/d), although direct comparative studies are not available.^2,4,5 Additionally, psycho-motor function assessed using DSST and SCT and next-day sedation assessed using VAS in patients receiving hypnotic doses of doxepin (1 and 3 mg) were the same as placebo. Two studies noted small-to-modest decreases in DSST, SCT, and VAS when doxepin, 6 mg, was administered.¹ Patients taking doxepin at antidepressant doses report significant anticholinergic side effects, including sedation, confusion, urinary retention, constipation, blurred vision, and dry mouth. Hypotension also has been reported at antidepressant doses, and there seems to be a dose-dependant cardiotoxicity, with higher incidence of adverse effects occurring at higher doses of the drug.

Severe toxicity or death from overdose is presumably less likely with hypnotic doses of doxepin than with higher doses, although this has not been systematically explored. If an insomniac overdosed on a 30-day supply of an hypnotic dose (3 or 6 mg), he or she would take only 90 to 180 mg of doxepin, which would be unlikely to cause severe toxicity or death.^2-4

Symptoms of withdrawal and rebound insomnia—an increase in WASO compared with baseline after discontinuing the medication—were assessed in a 35-day double-blind study of adults with chronic insomnia.¹ There was no evidence of withdrawal syndrome as measured by Tyler’s Symptom Checklist after doxepin 3 mg and 6 mg was discontinued. Discontinuation period-emergent nausea and vomiting was noted in 5% of patients taking 6 mg of doxepin, but not in those taking placebo or 3 mg of doxepin. There was no evidence of rebound insomnia after doxepin 3 mg and 6 mg was discontinued.¹

Contraindications

Doxepin is contraindicated in patients with hypersensitivity to doxepin hydrochloride, with severe urinary retention, with narrow angle glaucoma, and who have used monoamine oxidase inhibitors (MAOIs) within the previous 2 weeks. Serious adverse effects, including hypertensive crisis and death, have been reported with coadministration of MAOIs and certain drugs, such as serotonergic antidepressants and some opioids derivatives. There are no reports of concomitant use of doxepin with MAOIs.¹

Dosing

In adults, the recommended hypnotic dose for doxepin is 6 mg taken 30 minutes before bedtime. For patients age ≥65, the recommended starting hypnotic dose is 3 mg 30 minutes before bedtime, which can be increased to 6 mg if indicated.¹

Related Resources

• Doghramji K, Grewal R, Markov D. Evaluation and management of insomnia in the psychiatric setting. Focus. 2009;8(4):441-454.
• Psychiatric Clinics of North America. December 2006. All articles in this issue address sleep disorders encountered in psychiatric practice.
• National Sleep Foundation. www.sleepfoundation.org.

Drug Brand Names

• Amitriptyline • Elavil
• Cimetidine • Tagamet
• Desipramine • Norpramin
• Doxepin (3 mg and 6 mg) • Silenor
• Doxepin (10 to 150 mg, oral) • Sinequan
• Doxepin cream • Prudoxin
• Fluoxetine • Prozac
• Paroxetine • Paxil
• Ramelteon • Rozerem

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Low-dose doxepin—3 mg and 6 mg—has demonstrated efficacy for insomnia characterized by frequent or early-morning awakenings and an inability to return to sleep (Table 1).¹ FDA-approved in March 2010, doxepin (3 mg and 6 mg) is only the second insomnia medication not designated as a controlled substance and thus may be of special value in patients with a history of substance abuse.

Table 1

Doxepin: Fast facts

Clinical implications

Ramelteon, the other hypnotic that is not a controlled substance, is indicated for sleep initiation insomnia (ie, inability to fall asleep). In contrast, low-dose doxepin is for patients with sleep maintenance insomnia, which is waking up frequently or early in the morning and not falling back asleep.^1,2 A tricyclic antidepressant first approved in 1969, doxepin has long been available in larger doses (10-, 25-, 50-, 75-, 100-, and 150-mg capsules) to treat depression and anxiety and as a topical preparation (5% cream) for pruritus, but not in dosages <10 mg. An inexpensive generic doxepin oral solution (10 mg/ml) is available and can be titrated to smaller dosages by a dropper. Liquid doxepin costs 10 to 20 cents per dose. A pharmacist can provide a dropper, and patients should mix the medication in 4 ounces of water, milk, or juice; 0.3 ml of liquid doxepin contains 3 mg of active ingredient and 0.6 ml of solution contains 6 mg of doxepin. These other dosage forms of doxepin, however, are not FDA-approved for insomnia. (The retail price of low-dose doxepin was not available when this article went to press.)

How it works

Doxepin’s mechanism of action for treating depression and insomnia remains unknown. The antidepressant effect of doxepin is thought to result from inhibition of serotonin and norepinephrine reuptake at the synaptic cleft. Animal studies have shown anticholinergic and antihistaminergic activity with doxepin.² Doxepin is a potent histamine antagonist—predominantly at the H1 receptor—and its binding potency to the H1 receptor is approximately 100-times higher than its binding potency for monoamine transporters (serotonin and norepinephrine).^2,3 Brain histamine is believed to be 1 of the key elements in maintaining wakefulness, and the activation of the H1 receptor is thought to play an important role in mediating arousal. Blockade of the H1 receptor by doxepin likely plays a role in reducing wakefulness. Typically, therapeutic doses of antidepressants with anti-histaminergic properties, such as doxepin at antidepressant doses, amitriptyline, or desipramine, do not selectively block H1 receptors, but act at cholinergic, serotonergic, adrenergic, histaminergic, and muscarinic receptors, which can cause adverse effects.³ However, low doses of doxepin (1, 3, and 6 mg) can achieve selective H1 blockade.^4,5 Patients taking >25 mg/d of doxepin may report clinically significant anticholinergic effects.

Pharmacokinetics

When doxepin, 6 mg, was administered to healthy, fasting patients, time to maximum concentration (Tmax) was 3.5 hours. Peak plasma concentration (Cmax) increased in a dose-related fashion when doxepin was increased from 3 mg to 6 mg. Doxepin, 6 mg, taken with a high-fat meal resulted in area under the curve increase of 41%, Cmax increase of 15%, and almost 3-hour delay in Tmax. Therefore, to prevent a delay in onset of action and to minimize the likelihood of daytime sedation, doxepin should not be taken within 3 hours of a meal.^1-3

Doxepin is metabolized primarily by the liver’s cytochrome P450 (CYP) 2C19 and CYP2D6 enzymes; CYP1A2 and CYP2D6 are involved to a lesser extent. If doxepin is coadministered with drugs that inhibit these isoenzymes, such as fluoxetine and paroxetine, doxepin blood levels may increase. Doxepin does not seem to induce CYP isoenzymes. This medication is metabolized by demethylation and oxidation; the primary metabolite is nordoxepin (N-desmethyldoxepin), which later undergoes glucuronide conjugation. The half-life is 15 hours for doxepin and 31 hours for nordoxepin. Doxepin is excreted in urine primarily as glucuronide conjugate.^1-3

Coadministration with cimetidine, an inhibitor of CYP isoenzymes, could double the doxepin plasma concentration; therefore, patients taking cimetidine should not exceed 3 mg/d of doxepin.

Efficacy

Doxepin reduced insomnia symptoms in 3 pilot studies at doses of 10, 25, and 50 mg, and in 2 phase III randomized, double-blind, placebo-controlled clinical trials using 1, 3, and 6 mg (Table 2).^4,5 Clinical studies lasted up to 3 months.^1-3,6-8

In the first phase III trial, 67 patients, age 18 to 64 with chronic primary insomnia, were randomly assigned to placebo or 1 mg, 3 mg, or 6 mg of doxepin for 2 nights. All patients received all treatments, and each treatment was followed by 8 hours of polysomnography (PSG) evaluation in a sleep laboratory.⁴ In this study, patients taking doxepin at all doses achieved improvement in objective (PSG-defined) and subjective (patient-reported) measures of sleep duration and sleep maintenance. Wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE) improved with all doxepin doses, and wake time during sleep (WTDS)—which was the primary study endpoint—decreased with 3 mg and 6 mg doses, but not with 1 mg or placebo. In addition, PSG indicators of early-morning awakenings (terminal insomnia) were reduced, as shown by an increase in SE during the final third of the night and the 7^th and 8^th hours of sleep (1, 3, and 6 mg doses) and a reduction in wake time after sleep (WTAS) during the final third of the night (6 mg only). The effects on sleep duration and maintenance were more robust with 3 mg and 6 mg doses. Improved sleep onset was seen only with the 6 mg dose. Next-day alertness was assessed using the Visual Analogue Scale (VAS) for sleepiness, and the Digit-Symbol Substitution Test (DSST) and the Symbol-Copying Task (SCT) for psychomotor function. No statistically significant differences were found among placebo and any of the doxepin doses on the VAS, DSST, or SCT.

Doxepin was well tolerated. Reported adverse events were mild or moderate. Headaches and somnolence were reported by >2% of patients. The incidence of adverse events, including next-day sedation, was similar to that of placebo. Additionally, there were no spontaneous reports of anticholinergic side effects, which are associated with higher doxepin doses.⁴

The second phase III trial examined safety and efficacy of 1, 3, and 6 mg doxepin in patients age ≥65.⁵ Seventy-six adults with primary insomnia were randomly assigned to receive placebo or doxepin for 2 nights; all patients received all treatments, and each treatment was followed by an 8-hour PSG. Patients taking any doxepin dose achieved objective and subjective improvement in sleep duration and sleep maintenance, which lasted into the final hours of the night. WTDS (primary study endpoint), WASO, TST, and overall SE improved at all doxepin doses compared with placebo, and WTAS and SE at hours 7 and 8 improved at doxepin doses of 3 mg and 6 mg compared with placebo. These findings suggest that doxepin, 3 mg and 6 mg, can help older insomnia patients with early morning awakenings.

In this study, no statistically significant differences were found among placebo and any doxepin doses on VAS, DSST, or SCT or next-day residual sedation. The incidence of side effects was low and similar to that of placebo. Adverse events were mild or moderate; 1 incident of chest pain was reported, but it was determined not to be of cardiac origin and not related to study drug. There were no spontaneous reports of anticholinergic side effects associated with higher doses of doxepin. There were no reports of memory impairment.⁵

Table 2

Evidence of effectiveness of doxepin for insomnia

Tolerability

Clinical studies that evaluated the safety of doxepin lasted up to 3 months. Somnolence/sedation, nausea, and upper respiratory tract infection were reported by >2% of patients taking doxepin and were more common than in patients treated with placebo.¹ All reported adverse events were mild to moderate.

Doxepin appears to be better tolerated at hypnotic doses (3 mg and 6 mg) than at antidepressant doses (50 to 300 mg/d), although direct comparative studies are not available.^2,4,5 Additionally, psycho-motor function assessed using DSST and SCT and next-day sedation assessed using VAS in patients receiving hypnotic doses of doxepin (1 and 3 mg) were the same as placebo. Two studies noted small-to-modest decreases in DSST, SCT, and VAS when doxepin, 6 mg, was administered.¹ Patients taking doxepin at antidepressant doses report significant anticholinergic side effects, including sedation, confusion, urinary retention, constipation, blurred vision, and dry mouth. Hypotension also has been reported at antidepressant doses, and there seems to be a dose-dependant cardiotoxicity, with higher incidence of adverse effects occurring at higher doses of the drug.

Severe toxicity or death from overdose is presumably less likely with hypnotic doses of doxepin than with higher doses, although this has not been systematically explored. If an insomniac overdosed on a 30-day supply of an hypnotic dose (3 or 6 mg), he or she would take only 90 to 180 mg of doxepin, which would be unlikely to cause severe toxicity or death.^2-4

Symptoms of withdrawal and rebound insomnia—an increase in WASO compared with baseline after discontinuing the medication—were assessed in a 35-day double-blind study of adults with chronic insomnia.¹ There was no evidence of withdrawal syndrome as measured by Tyler’s Symptom Checklist after doxepin 3 mg and 6 mg was discontinued. Discontinuation period-emergent nausea and vomiting was noted in 5% of patients taking 6 mg of doxepin, but not in those taking placebo or 3 mg of doxepin. There was no evidence of rebound insomnia after doxepin 3 mg and 6 mg was discontinued.¹

Contraindications

Doxepin is contraindicated in patients with hypersensitivity to doxepin hydrochloride, with severe urinary retention, with narrow angle glaucoma, and who have used monoamine oxidase inhibitors (MAOIs) within the previous 2 weeks. Serious adverse effects, including hypertensive crisis and death, have been reported with coadministration of MAOIs and certain drugs, such as serotonergic antidepressants and some opioids derivatives. There are no reports of concomitant use of doxepin with MAOIs.¹

Dosing

In adults, the recommended hypnotic dose for doxepin is 6 mg taken 30 minutes before bedtime. For patients age ≥65, the recommended starting hypnotic dose is 3 mg 30 minutes before bedtime, which can be increased to 6 mg if indicated.¹

Related Resources

• Doghramji K, Grewal R, Markov D. Evaluation and management of insomnia in the psychiatric setting. Focus. 2009;8(4):441-454.
• Psychiatric Clinics of North America. December 2006. All articles in this issue address sleep disorders encountered in psychiatric practice.
• National Sleep Foundation. www.sleepfoundation.org.

Drug Brand Names

• Amitriptyline • Elavil
• Cimetidine • Tagamet
• Desipramine • Norpramin
• Doxepin (3 mg and 6 mg) • Silenor
• Doxepin (10 to 150 mg, oral) • Sinequan
• Doxepin cream • Prudoxin
• Fluoxetine • Prozac
• Paroxetine • Paxil
• Ramelteon • Rozerem

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Low-dose doxepin—3 mg and 6 mg—has demonstrated efficacy for insomnia characterized by frequent or early-morning awakenings and an inability to return to sleep (Table 1).¹ FDA-approved in March 2010, doxepin (3 mg and 6 mg) is only the second insomnia medication not designated as a controlled substance and thus may be of special value in patients with a history of substance abuse.

Table 1

Doxepin: Fast facts

Clinical implications

Ramelteon, the other hypnotic that is not a controlled substance, is indicated for sleep initiation insomnia (ie, inability to fall asleep). In contrast, low-dose doxepin is for patients with sleep maintenance insomnia, which is waking up frequently or early in the morning and not falling back asleep.^1,2 A tricyclic antidepressant first approved in 1969, doxepin has long been available in larger doses (10-, 25-, 50-, 75-, 100-, and 150-mg capsules) to treat depression and anxiety and as a topical preparation (5% cream) for pruritus, but not in dosages <10 mg. An inexpensive generic doxepin oral solution (10 mg/ml) is available and can be titrated to smaller dosages by a dropper. Liquid doxepin costs 10 to 20 cents per dose. A pharmacist can provide a dropper, and patients should mix the medication in 4 ounces of water, milk, or juice; 0.3 ml of liquid doxepin contains 3 mg of active ingredient and 0.6 ml of solution contains 6 mg of doxepin. These other dosage forms of doxepin, however, are not FDA-approved for insomnia. (The retail price of low-dose doxepin was not available when this article went to press.)

How it works

Doxepin’s mechanism of action for treating depression and insomnia remains unknown. The antidepressant effect of doxepin is thought to result from inhibition of serotonin and norepinephrine reuptake at the synaptic cleft. Animal studies have shown anticholinergic and antihistaminergic activity with doxepin.² Doxepin is a potent histamine antagonist—predominantly at the H1 receptor—and its binding potency to the H1 receptor is approximately 100-times higher than its binding potency for monoamine transporters (serotonin and norepinephrine).^2,3 Brain histamine is believed to be 1 of the key elements in maintaining wakefulness, and the activation of the H1 receptor is thought to play an important role in mediating arousal. Blockade of the H1 receptor by doxepin likely plays a role in reducing wakefulness. Typically, therapeutic doses of antidepressants with anti-histaminergic properties, such as doxepin at antidepressant doses, amitriptyline, or desipramine, do not selectively block H1 receptors, but act at cholinergic, serotonergic, adrenergic, histaminergic, and muscarinic receptors, which can cause adverse effects.³ However, low doses of doxepin (1, 3, and 6 mg) can achieve selective H1 blockade.^4,5 Patients taking >25 mg/d of doxepin may report clinically significant anticholinergic effects.

Pharmacokinetics

When doxepin, 6 mg, was administered to healthy, fasting patients, time to maximum concentration (Tmax) was 3.5 hours. Peak plasma concentration (Cmax) increased in a dose-related fashion when doxepin was increased from 3 mg to 6 mg. Doxepin, 6 mg, taken with a high-fat meal resulted in area under the curve increase of 41%, Cmax increase of 15%, and almost 3-hour delay in Tmax. Therefore, to prevent a delay in onset of action and to minimize the likelihood of daytime sedation, doxepin should not be taken within 3 hours of a meal.^1-3

Doxepin is metabolized primarily by the liver’s cytochrome P450 (CYP) 2C19 and CYP2D6 enzymes; CYP1A2 and CYP2D6 are involved to a lesser extent. If doxepin is coadministered with drugs that inhibit these isoenzymes, such as fluoxetine and paroxetine, doxepin blood levels may increase. Doxepin does not seem to induce CYP isoenzymes. This medication is metabolized by demethylation and oxidation; the primary metabolite is nordoxepin (N-desmethyldoxepin), which later undergoes glucuronide conjugation. The half-life is 15 hours for doxepin and 31 hours for nordoxepin. Doxepin is excreted in urine primarily as glucuronide conjugate.^1-3

Coadministration with cimetidine, an inhibitor of CYP isoenzymes, could double the doxepin plasma concentration; therefore, patients taking cimetidine should not exceed 3 mg/d of doxepin.

Efficacy

Doxepin reduced insomnia symptoms in 3 pilot studies at doses of 10, 25, and 50 mg, and in 2 phase III randomized, double-blind, placebo-controlled clinical trials using 1, 3, and 6 mg (Table 2).^4,5 Clinical studies lasted up to 3 months.^1-3,6-8

In the first phase III trial, 67 patients, age 18 to 64 with chronic primary insomnia, were randomly assigned to placebo or 1 mg, 3 mg, or 6 mg of doxepin for 2 nights. All patients received all treatments, and each treatment was followed by 8 hours of polysomnography (PSG) evaluation in a sleep laboratory.⁴ In this study, patients taking doxepin at all doses achieved improvement in objective (PSG-defined) and subjective (patient-reported) measures of sleep duration and sleep maintenance. Wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE) improved with all doxepin doses, and wake time during sleep (WTDS)—which was the primary study endpoint—decreased with 3 mg and 6 mg doses, but not with 1 mg or placebo. In addition, PSG indicators of early-morning awakenings (terminal insomnia) were reduced, as shown by an increase in SE during the final third of the night and the 7^th and 8^th hours of sleep (1, 3, and 6 mg doses) and a reduction in wake time after sleep (WTAS) during the final third of the night (6 mg only). The effects on sleep duration and maintenance were more robust with 3 mg and 6 mg doses. Improved sleep onset was seen only with the 6 mg dose. Next-day alertness was assessed using the Visual Analogue Scale (VAS) for sleepiness, and the Digit-Symbol Substitution Test (DSST) and the Symbol-Copying Task (SCT) for psychomotor function. No statistically significant differences were found among placebo and any of the doxepin doses on the VAS, DSST, or SCT.

Doxepin was well tolerated. Reported adverse events were mild or moderate. Headaches and somnolence were reported by >2% of patients. The incidence of adverse events, including next-day sedation, was similar to that of placebo. Additionally, there were no spontaneous reports of anticholinergic side effects, which are associated with higher doxepin doses.⁴

The second phase III trial examined safety and efficacy of 1, 3, and 6 mg doxepin in patients age ≥65.⁵ Seventy-six adults with primary insomnia were randomly assigned to receive placebo or doxepin for 2 nights; all patients received all treatments, and each treatment was followed by an 8-hour PSG. Patients taking any doxepin dose achieved objective and subjective improvement in sleep duration and sleep maintenance, which lasted into the final hours of the night. WTDS (primary study endpoint), WASO, TST, and overall SE improved at all doxepin doses compared with placebo, and WTAS and SE at hours 7 and 8 improved at doxepin doses of 3 mg and 6 mg compared with placebo. These findings suggest that doxepin, 3 mg and 6 mg, can help older insomnia patients with early morning awakenings.

In this study, no statistically significant differences were found among placebo and any doxepin doses on VAS, DSST, or SCT or next-day residual sedation. The incidence of side effects was low and similar to that of placebo. Adverse events were mild or moderate; 1 incident of chest pain was reported, but it was determined not to be of cardiac origin and not related to study drug. There were no spontaneous reports of anticholinergic side effects associated with higher doses of doxepin. There were no reports of memory impairment.⁵

Table 2

Evidence of effectiveness of doxepin for insomnia

Tolerability

Clinical studies that evaluated the safety of doxepin lasted up to 3 months. Somnolence/sedation, nausea, and upper respiratory tract infection were reported by >2% of patients taking doxepin and were more common than in patients treated with placebo.¹ All reported adverse events were mild to moderate.

Doxepin appears to be better tolerated at hypnotic doses (3 mg and 6 mg) than at antidepressant doses (50 to 300 mg/d), although direct comparative studies are not available.^2,4,5 Additionally, psycho-motor function assessed using DSST and SCT and next-day sedation assessed using VAS in patients receiving hypnotic doses of doxepin (1 and 3 mg) were the same as placebo. Two studies noted small-to-modest decreases in DSST, SCT, and VAS when doxepin, 6 mg, was administered.¹ Patients taking doxepin at antidepressant doses report significant anticholinergic side effects, including sedation, confusion, urinary retention, constipation, blurred vision, and dry mouth. Hypotension also has been reported at antidepressant doses, and there seems to be a dose-dependant cardiotoxicity, with higher incidence of adverse effects occurring at higher doses of the drug.

Severe toxicity or death from overdose is presumably less likely with hypnotic doses of doxepin than with higher doses, although this has not been systematically explored. If an insomniac overdosed on a 30-day supply of an hypnotic dose (3 or 6 mg), he or she would take only 90 to 180 mg of doxepin, which would be unlikely to cause severe toxicity or death.^2-4

Symptoms of withdrawal and rebound insomnia—an increase in WASO compared with baseline after discontinuing the medication—were assessed in a 35-day double-blind study of adults with chronic insomnia.¹ There was no evidence of withdrawal syndrome as measured by Tyler’s Symptom Checklist after doxepin 3 mg and 6 mg was discontinued. Discontinuation period-emergent nausea and vomiting was noted in 5% of patients taking 6 mg of doxepin, but not in those taking placebo or 3 mg of doxepin. There was no evidence of rebound insomnia after doxepin 3 mg and 6 mg was discontinued.¹

Contraindications

Doxepin is contraindicated in patients with hypersensitivity to doxepin hydrochloride, with severe urinary retention, with narrow angle glaucoma, and who have used monoamine oxidase inhibitors (MAOIs) within the previous 2 weeks. Serious adverse effects, including hypertensive crisis and death, have been reported with coadministration of MAOIs and certain drugs, such as serotonergic antidepressants and some opioids derivatives. There are no reports of concomitant use of doxepin with MAOIs.¹

Dosing

In adults, the recommended hypnotic dose for doxepin is 6 mg taken 30 minutes before bedtime. For patients age ≥65, the recommended starting hypnotic dose is 3 mg 30 minutes before bedtime, which can be increased to 6 mg if indicated.¹

Related Resources

• Doghramji K, Grewal R, Markov D. Evaluation and management of insomnia in the psychiatric setting. Focus. 2009;8(4):441-454.
• Psychiatric Clinics of North America. December 2006. All articles in this issue address sleep disorders encountered in psychiatric practice.
• National Sleep Foundation. www.sleepfoundation.org.

Drug Brand Names

• Amitriptyline • Elavil
• Cimetidine • Tagamet
• Desipramine • Norpramin
• Doxepin (3 mg and 6 mg) • Silenor
• Doxepin (10 to 150 mg, oral) • Sinequan
• Doxepin cream • Prudoxin
• Fluoxetine • Prozac
• Paroxetine • Paxil
• Ramelteon • Rozerem

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

In Drs. Ali M. Hashmi and Dennis Vowell’s article “The manipulative self-harmer” (Cases That Test Your Skills, Current Psychiatry, June 2010, p. 44-48), the authors regard the patient’s outcome (“Recently she was placed in a more restrictive setting because her hostile and self-destructive behavior escalated”) as characteristic of borderline personality disorder (BPD) (“Ms. L is no different from most axis II Cluster B disordered patients.”). In my view, this is the greatest risk of calling a patient borderline—it tends to justify poor outcomes by thinking that it is just characteristic of the illness. Instead, shouldn’t we worry that our treatment may be suboptimal? Maybe we are missing something?

For example, Ms. L may have some degree of bipolarity (see the Harvard Bipolarity Index as a characterization of that concept, incorporating but going beyond the DSM-IV-TR) that could account for their observation, “Her mood and behavior continue to oscillate; she is relatively calm and satisfied 1 week, angry and assaultive the next.” Instead of concluding, “this stormy course is expected…” the authors should be wondering whether they might be contributing to it by restarting venlafaxine despite simultaneous carbamazepine initiation. Granted, the possibilities of bipolarity and antidepressant-induced rapid cycling are complex considerations, because we lack solid footing for differentiating BPD and bipolar disorder and for determining causality when a patient experiences rapid mood changes while taking an antidepressant. These are controversial issues, but why present the case as though it’s illustrative of accepted principles? I find it perfectly illustrative of how badly we’re floundering as a field.

Jim Phelps, MD
PsychEducation.org
Corvallis, OR

The authors respond

Dr. Phelps’ contention is that our observation that Ms. L’s “hostile and self-destructive behavior” makes her “no different from most axis II Cluster B disordered patients” somehow understates the extent of her illness, perhaps leading to poorer outcomes. Negative countertransference toward such patients is the norm and handling it empathically is an integral part of the treatment relationship. This is true even though the severity of Ms. L’s personality pathology, as evidenced by her placement in the “911 program,” may not be representative of all patients with BPD.

We agree that “the possibilities of…antidepressant-induced rapid cycling are complex considerations.” Even experts disagree on this. In fact, as we pointed out, Ms. L resisted medication tapers, at one point insisting that high doses of fluoxetine and venafaxine be used together for depression, a request we denied specifically for fear of worsening her mood lability. Fluoxetine was discontinued and venlafaxine restarted at a lower dose to treat her persistent depression as well as to help with her chronic back pain. Because by this time she was taking carbamazepine as well, we felt the risk was acceptable. Her positive long-term outcome has validated our approach.

We disagree that psychiatry is “floundering” as a field. In fact, exchanges like this are a core component of placing our specialty on a more solid, scientific basis to position it for future challenges.

Ali M. Hashmi, MD
Medical director
Mid-South Health Systems
Jonesboro, AR
Clinical instructor
Department of psychiatry
University of Arkansas for Medical Science
College of Medicine
Little Rock, AR

Dennis Vowell, PsyD
Clinical psychologist
Mid-South Health Systems
Paragould, AR

In Drs. Ali M. Hashmi and Dennis Vowell’s article “The manipulative self-harmer” (Cases That Test Your Skills, Current Psychiatry, June 2010, p. 44-48), the authors regard the patient’s outcome (“Recently she was placed in a more restrictive setting because her hostile and self-destructive behavior escalated”) as characteristic of borderline personality disorder (BPD) (“Ms. L is no different from most axis II Cluster B disordered patients.”). In my view, this is the greatest risk of calling a patient borderline—it tends to justify poor outcomes by thinking that it is just characteristic of the illness. Instead, shouldn’t we worry that our treatment may be suboptimal? Maybe we are missing something?

For example, Ms. L may have some degree of bipolarity (see the Harvard Bipolarity Index as a characterization of that concept, incorporating but going beyond the DSM-IV-TR) that could account for their observation, “Her mood and behavior continue to oscillate; she is relatively calm and satisfied 1 week, angry and assaultive the next.” Instead of concluding, “this stormy course is expected…” the authors should be wondering whether they might be contributing to it by restarting venlafaxine despite simultaneous carbamazepine initiation. Granted, the possibilities of bipolarity and antidepressant-induced rapid cycling are complex considerations, because we lack solid footing for differentiating BPD and bipolar disorder and for determining causality when a patient experiences rapid mood changes while taking an antidepressant. These are controversial issues, but why present the case as though it’s illustrative of accepted principles? I find it perfectly illustrative of how badly we’re floundering as a field.

Jim Phelps, MD
PsychEducation.org
Corvallis, OR

The authors respond

Dr. Phelps’ contention is that our observation that Ms. L’s “hostile and self-destructive behavior” makes her “no different from most axis II Cluster B disordered patients” somehow understates the extent of her illness, perhaps leading to poorer outcomes. Negative countertransference toward such patients is the norm and handling it empathically is an integral part of the treatment relationship. This is true even though the severity of Ms. L’s personality pathology, as evidenced by her placement in the “911 program,” may not be representative of all patients with BPD.

We agree that “the possibilities of…antidepressant-induced rapid cycling are complex considerations.” Even experts disagree on this. In fact, as we pointed out, Ms. L resisted medication tapers, at one point insisting that high doses of fluoxetine and venafaxine be used together for depression, a request we denied specifically for fear of worsening her mood lability. Fluoxetine was discontinued and venlafaxine restarted at a lower dose to treat her persistent depression as well as to help with her chronic back pain. Because by this time she was taking carbamazepine as well, we felt the risk was acceptable. Her positive long-term outcome has validated our approach.

We disagree that psychiatry is “floundering” as a field. In fact, exchanges like this are a core component of placing our specialty on a more solid, scientific basis to position it for future challenges.

Ali M. Hashmi, MD
Medical director
Mid-South Health Systems
Jonesboro, AR
Clinical instructor
Department of psychiatry
University of Arkansas for Medical Science
College of Medicine
Little Rock, AR

Dennis Vowell, PsyD
Clinical psychologist
Mid-South Health Systems
Paragould, AR

In Drs. Ali M. Hashmi and Dennis Vowell’s article “The manipulative self-harmer” (Cases That Test Your Skills, Current Psychiatry, June 2010, p. 44-48), the authors regard the patient’s outcome (“Recently she was placed in a more restrictive setting because her hostile and self-destructive behavior escalated”) as characteristic of borderline personality disorder (BPD) (“Ms. L is no different from most axis II Cluster B disordered patients.”). In my view, this is the greatest risk of calling a patient borderline—it tends to justify poor outcomes by thinking that it is just characteristic of the illness. Instead, shouldn’t we worry that our treatment may be suboptimal? Maybe we are missing something?

For example, Ms. L may have some degree of bipolarity (see the Harvard Bipolarity Index as a characterization of that concept, incorporating but going beyond the DSM-IV-TR) that could account for their observation, “Her mood and behavior continue to oscillate; she is relatively calm and satisfied 1 week, angry and assaultive the next.” Instead of concluding, “this stormy course is expected…” the authors should be wondering whether they might be contributing to it by restarting venlafaxine despite simultaneous carbamazepine initiation. Granted, the possibilities of bipolarity and antidepressant-induced rapid cycling are complex considerations, because we lack solid footing for differentiating BPD and bipolar disorder and for determining causality when a patient experiences rapid mood changes while taking an antidepressant. These are controversial issues, but why present the case as though it’s illustrative of accepted principles? I find it perfectly illustrative of how badly we’re floundering as a field.

Jim Phelps, MD
PsychEducation.org
Corvallis, OR

The authors respond

Dr. Phelps’ contention is that our observation that Ms. L’s “hostile and self-destructive behavior” makes her “no different from most axis II Cluster B disordered patients” somehow understates the extent of her illness, perhaps leading to poorer outcomes. Negative countertransference toward such patients is the norm and handling it empathically is an integral part of the treatment relationship. This is true even though the severity of Ms. L’s personality pathology, as evidenced by her placement in the “911 program,” may not be representative of all patients with BPD.

We agree that “the possibilities of…antidepressant-induced rapid cycling are complex considerations.” Even experts disagree on this. In fact, as we pointed out, Ms. L resisted medication tapers, at one point insisting that high doses of fluoxetine and venafaxine be used together for depression, a request we denied specifically for fear of worsening her mood lability. Fluoxetine was discontinued and venlafaxine restarted at a lower dose to treat her persistent depression as well as to help with her chronic back pain. Because by this time she was taking carbamazepine as well, we felt the risk was acceptable. Her positive long-term outcome has validated our approach.

We disagree that psychiatry is “floundering” as a field. In fact, exchanges like this are a core component of placing our specialty on a more solid, scientific basis to position it for future challenges.

Ali M. Hashmi, MD
Medical director
Mid-South Health Systems
Jonesboro, AR
Clinical instructor
Department of psychiatry
University of Arkansas for Medical Science
College of Medicine
Little Rock, AR

Dennis Vowell, PsyD
Clinical psychologist
Mid-South Health Systems
Paragould, AR

The number of people with psychiatric disorders who use complementary and alternative medicine (CAM) is on the rise. In surveys of patients seeking psychiatric care, estimates of CAM use range from 8% to 57%; the most frequent uses are for depression and anxiety disorders. A population-based study in the United States found that 9% of respondents had anxiety attacks and 57% of these individuals had used CAM.¹ Similarly, in a Finnish population-based study (N=5,987) 35% of subjects reported some form of CAM use in the previous year; those with comorbid anxiety and depressive disorders used CAM most frequently.²

Unfortunately, a MEDLINE search shows that the number of studies examining psychotropic medications dwarfs the number of studies on even the most common CAM treatments used for psychiatric disorders. Far more patients with diagnosed mental disorders are studied in trials of standard treatments than CAM treatments. Because very few studies evaluate the cost-effectiveness of CAM treatments for psychiatric disorders, the risk-to-benefit ratio is difficult to calculate. Although several CAM treatments for depressive disorders have enough support to be considered options,³ CAM options for anxiety disorders are fewer and have less evidence of efficacy.

For these reasons, it is hard to recommend any CAM treatment as first line. Despite the relative lack of high quality research on CAM treatment outcomes, high rates of CAM use make it critical for clinicians to understand what treatments are available—or at least which treatments should be favored if patients are intent on trying them. We review the current research for yoga, exercise, bibliotherapy, and the dietary supplements kava and inositol for treating anxiety disorders and suggest those that warrant consideration for patients who do not respond, respond partially, or suffer from side effects from selective serotonin reuptake inhibitors (SSRIs) or benzodiazepines.

Limitations of CAM research

There are several limitations to the research literature on CAM approaches for anxiety disorders.⁴ First, there is a wide diversity of practices considered alternative or complementary and various ways in which these methods are applied across cultures. Some authors consider complementary medicines to be only herbal remedies, whereas others include individual therapies such as acupuncture, aromatherapy, herbal therapy, homeopathy, iridology, naturopathy, and reflexology.⁵ This article defines “alternative” treatments as those other than a form of psychotherapy or an FDA-approved medication that substitute for standard psychiatric treatment, and “complementary” approaches as those used to augment standard psychiatric treatments.

Anxiety and stress are ubiquitous, perhaps motivating interest in CAM options and prompting research on heterogeneous groups of individuals with poorly defined clinical syndromes or with isolated symptoms of anxiety or subjective distress. Few studies examine well-defined patient groups with diagnosed anxiety disorders. There are also multiple research design problems, including poorly specified treatments, poorly chosen placebos, and interpreting nonsignificant differences from established treatments as equivalence in underpowered studies.

The CAM treatments reviewed in this article have ≥2 randomized controlled trials (RCTs) that support their use for patients with diagnosed anxiety disorders, and ≥1 study that shows that the treatment can induce remission.

Yoga

In 2005 Kirkwood et al carried out the first systematic review of research evidence for the effectiveness of yoga in anxiety treatment.⁶ Of 19 studies identified, 4 RCTs and 1 nonrandomized trial met their inclusion criteria, which were an anxiety disorder diagnosis, use of yoga or yoga-based exercises alone, and anxiety rating scales used as outcome measures. Most found significant improvement in anxiety symptoms with yoga compared with placebo. Details of the 5 trials evaluated in Kirkwood’s review are summarized in Table 1.^7-11

Since the 2005 review, 3 additional studies of yoga and anxiety have been published, but none would meet Kirkwood’s inclusion criteria. One that evaluated a heterogeneous group of patients using an intervention with multiple components—only 1 of which was yoga—found the intervention significantly reduced anxiety scores.¹² A second study comparing yoga with relaxation in 131 patients with mild-to-moderate stress but no anxiety disorder diagnosis showed yoga was as effective as relaxation in improving anxiety symptoms as measured by the anxiety subscale of the State Trait Personality Inventory.¹³ In a study of 183 nonrandomized survivors of the 2004 southeast Asia tsunami with posttraumatic stress disorder (PTSD) symptoms, yoga-based breathing either alone or paired with trauma reduction exposure techniques significantly reduced PTSD symptoms compared with wait-list controls.¹⁴

Conclusion. Few controlled studies evaluated yoga for anxiety disorders, and all have significant methodologic limitations and/or poor methodology reporting. The diagnostic conditions treated and both yoga interventions and control conditions varied. However, these limited results are encouraging, particularly for treatment of obsessive-compulsive disorder (OCD). There is little information regarding safety or contraindications of yoga. Reported attrition rates were high in most studies, which may raise concerns about patient motivation and compliance.

Table 1

Evidence on the effectiveness of yoga for anxiety disorders

Exercise

The literature examining the relationship between exercise and depression is extensive, but much less has been published about exercise in patients with anxiety disorders (Table 2).^15-17 In a 10-week trial, Broocks and colleagues compared clomipramine, exercise (running), and placebo in 46 outpatients with panic disorder.¹⁵ Both exercise and clomipramine, 112.5 mg/d, significantly reduced panic symptoms compared with placebo, but clomipramine was more effective and faster-acting.

A more recent RCT compared group cognitive-behavioral therapy (GCBT) plus a home-based walking program vs GCBT and in 21 patients with panic disorder, generalized anxiety disorder (GAD), or social phobia.¹⁶ Compared with GCBT plus educational sessions, GCBT plus walking had a significant effect on self-reported depression, anxiety, and stress. Results differed by diagnosis; the most marked effects occurred in individuals with social phobia, whereas benefits for those with panic disorder or GAD were questionable.

Fifteen patients with OCD were recruited to participate in a 12-week, moderate-intensity aerobic exercise program added to their standard behavioral and/or pharmacologic treatment.¹⁷ Subjects demonstrated improvement in negative mood, anxiety, obsessions, and compulsions after each exercise session. Changes after each session persisted over the 12-week intervention, although the magnitude attenuated over the duration of the intervention.

Conclusion. Although initial results from small trials suggest exercise may help improve anxiety symptoms, further studies are needed to determine how to best use exercise training to treat anxious patients, specifically regarding dose-response relationship, differences in effectiveness between aerobic and resistance training, and the mechanisms by which exercise improves psychiatric symptoms.

Table 2

Exercise for anxiety: More research is needed

Bibliotherapy

Investigation of bibliotherapy for treatment of anxiety disorders has been limited (Table 3).^18-20 A 2009 RCT demonstrated that for 21 patients with mild-to-moderate social phobia, bibliotherapy—in the form of an 8-week self-directed CBT program with minimal therapist involvement—was superior to a wait-list control and induced clinically significant change in approximately one-third of patients.²⁰

Rapee et al randomly assigned 267 children age 6 to 12 with anxiety disorders to bibliotherapy that consisted of parents treating their children in the home with written materials, 9 sessions of GCBT, or a wait-list control condition.¹⁹ Bibliotherapy provided by parents demonstrated benefit compared with wait-listing but was not as efficacious as GCBT at post-treatment and 3-month follow-up.

Lidren and colleagues randomly assigned 36 adult patients with panic disorder to bibliotherapy, group therapy combined with bibliotherapy, or a waitlist.¹⁸ Both treatments were more effective than wait-listing in reducing the frequency of panic attacks, severity of physical panic symptoms, catastrophic cognitions, agoraphobic avoidance, and depression. Both interventions maintained their effects at 3-and 6-month follow-up and produced clinically significant change in most patients.

Conclusion. Some preliminary evidence supports the effectiveness of bibliotherapy for social anxiety disorder, childhood anxiety disorders, and panic disorder.

Table 3

Preliminary evidence supports bibliotherapy for select anxiety disorders

Dietary supplements

Many dietary and herbal supplements are purported to have therapeutic efficacy for anxiety symptoms. Because of inadequate FDA regulation of manufacturing and marketing of these agents, most of these supplements have not been tested on patients with anxiety disorders.²¹ Limited evidence supports the use of kava for GAD and inositol for panic disorder (Table 4).^22-28

Kava. Multiple double-blind RCTs found kava (Piper methysticum)—a plant indigenous to South Pacific islands—has effects greater than placebo and comparable to standard treatments for mild to moderately severe GAD. A Cochrane meta-analysis²² of 11 trials with 645 participants concluded that kava is effective for reducing GAD symptoms, with risks comparable to standard treatments for up to 6 months of use.

Case reports of kava-associated liver toxicity led to a marketing ban in Canada in 2000, followed shortly by Germany, Australia, and the United Kingdom. In 2002 the FDA issued a Consumer Advisory²⁹ discouraging kava use. Since then a flurry of research has looked for sources of possible toxicity, including individual sensitivities,²⁹ excessive dosing, use of toxic parts of the kava plant instead of the roots,^30,31 interactions with other hepatoactive substances, and non-water based extraction methods. RCTs demonstrating kava’s efficacy and safety were characterized by careful dosing supervision, use of standardized kava extracts, and avoidance of interactions with other hepatoactive medications or CAM treatments. Doses ≤300 mg/d are recommended.²²

RCTs that used the standardized acetone extract WS1490²³ found that women and younger adults show more positive effects from kava, and showed no liver toxicity when used for 1 to 24 weeks. A recent RCT that used kava extracts obtained via water-based methods showed kava had significant anxiolytic effects.²⁴ However, a study of liver toxicity reports found that water-based extractions, acetonic extractions, and ethanol extractions all have been associated with toxic hepatic reactions.³² Aqueous extraction does not guarantee safety, and the extraction solvent does not cause toxicity. A recent report of a severe liver reaction to the native drink by a tourist in Samoa³³ suggests that aqueous extractions from the root stock— the type of kava used by South Pacific islanders—also can be unsafe.

Conclusion. Multiple RCTs have found kava relatively safe and effective for treating anxiety symptoms. Caution is necessary, however, because of reports of liver toxicity associated with its use. Physician oversight and monitoring of kava use are appropriate.

Inositol. Evidence from RCTs suggests inositol, a natural isomer of glucose and a precursor in the phosphatidylinositol cycle, can significantly improve panic disorder symptoms.^25-28 In 1 trial, efficacy and side effects were comparable to fluvoxamine.²⁸ Effective doses ranged from 12 g/d to 18 g/d. Researchers tested inositol as monotherapy or augmentation to SSRIs for patients with mild-to-moderate OCD. In small double-blind crossover RCTs, inositol monotherapy significantly reduced Yale-Brown Obsessive Compulsive Scale scores compared with placebo²⁶ but inositol augmentation added nothing to the effects of SSRIs.²⁷

Conclusion. Inositol appears to be effective in improving symptoms of panic disorder. Its use for other anxiety disorders is unproven.

Table 4

Dietary supplements for anxiety disorders

Supervision is recommended

The evidence base for most CAM interventions commonly used for anxiety is relatively poor and recent systematic reviews found few methodologically rigorous studies. This has not, however, diminished CAM treatments’ popularity. Despite a paucity of high-quality studies regarding CAM for anxiety disorders, there is enough data supporting yoga, exercise, bibliotherapy, kava, and inositol to allow psychiatrists to collaborate with patients who wish to try these treatments. Advise patients that they may need physician supervision similar to that used with standard psychiatric treatments.

Related Resources

• National Center for Complementary and Alternative Medicine. http://nccam.nih.gov.
• The Journal of Alternative and Complementary Medicine. www.liebertonline.com/loi/acm.
• MedlinePlus: Complementary and Alternative Medicine. www.nlm.nih.gov/medlineplus/complementaryandalternativemedicine.html.

Drug Brand Names

• Amitriptyline • Elavil
• Chlordiazepoxide • Librium
• Clomipramine • Anafranil
• Diazepam • Valium
• Fluvoxamine • Luvox

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

The number of people with psychiatric disorders who use complementary and alternative medicine (CAM) is on the rise. In surveys of patients seeking psychiatric care, estimates of CAM use range from 8% to 57%; the most frequent uses are for depression and anxiety disorders. A population-based study in the United States found that 9% of respondents had anxiety attacks and 57% of these individuals had used CAM.¹ Similarly, in a Finnish population-based study (N=5,987) 35% of subjects reported some form of CAM use in the previous year; those with comorbid anxiety and depressive disorders used CAM most frequently.²

Unfortunately, a MEDLINE search shows that the number of studies examining psychotropic medications dwarfs the number of studies on even the most common CAM treatments used for psychiatric disorders. Far more patients with diagnosed mental disorders are studied in trials of standard treatments than CAM treatments. Because very few studies evaluate the cost-effectiveness of CAM treatments for psychiatric disorders, the risk-to-benefit ratio is difficult to calculate. Although several CAM treatments for depressive disorders have enough support to be considered options,³ CAM options for anxiety disorders are fewer and have less evidence of efficacy.

For these reasons, it is hard to recommend any CAM treatment as first line. Despite the relative lack of high quality research on CAM treatment outcomes, high rates of CAM use make it critical for clinicians to understand what treatments are available—or at least which treatments should be favored if patients are intent on trying them. We review the current research for yoga, exercise, bibliotherapy, and the dietary supplements kava and inositol for treating anxiety disorders and suggest those that warrant consideration for patients who do not respond, respond partially, or suffer from side effects from selective serotonin reuptake inhibitors (SSRIs) or benzodiazepines.

Limitations of CAM research

There are several limitations to the research literature on CAM approaches for anxiety disorders.⁴ First, there is a wide diversity of practices considered alternative or complementary and various ways in which these methods are applied across cultures. Some authors consider complementary medicines to be only herbal remedies, whereas others include individual therapies such as acupuncture, aromatherapy, herbal therapy, homeopathy, iridology, naturopathy, and reflexology.⁵ This article defines “alternative” treatments as those other than a form of psychotherapy or an FDA-approved medication that substitute for standard psychiatric treatment, and “complementary” approaches as those used to augment standard psychiatric treatments.

Anxiety and stress are ubiquitous, perhaps motivating interest in CAM options and prompting research on heterogeneous groups of individuals with poorly defined clinical syndromes or with isolated symptoms of anxiety or subjective distress. Few studies examine well-defined patient groups with diagnosed anxiety disorders. There are also multiple research design problems, including poorly specified treatments, poorly chosen placebos, and interpreting nonsignificant differences from established treatments as equivalence in underpowered studies.

The CAM treatments reviewed in this article have ≥2 randomized controlled trials (RCTs) that support their use for patients with diagnosed anxiety disorders, and ≥1 study that shows that the treatment can induce remission.

Yoga

In 2005 Kirkwood et al carried out the first systematic review of research evidence for the effectiveness of yoga in anxiety treatment.⁶ Of 19 studies identified, 4 RCTs and 1 nonrandomized trial met their inclusion criteria, which were an anxiety disorder diagnosis, use of yoga or yoga-based exercises alone, and anxiety rating scales used as outcome measures. Most found significant improvement in anxiety symptoms with yoga compared with placebo. Details of the 5 trials evaluated in Kirkwood’s review are summarized in Table 1.^7-11

Since the 2005 review, 3 additional studies of yoga and anxiety have been published, but none would meet Kirkwood’s inclusion criteria. One that evaluated a heterogeneous group of patients using an intervention with multiple components—only 1 of which was yoga—found the intervention significantly reduced anxiety scores.¹² A second study comparing yoga with relaxation in 131 patients with mild-to-moderate stress but no anxiety disorder diagnosis showed yoga was as effective as relaxation in improving anxiety symptoms as measured by the anxiety subscale of the State Trait Personality Inventory.¹³ In a study of 183 nonrandomized survivors of the 2004 southeast Asia tsunami with posttraumatic stress disorder (PTSD) symptoms, yoga-based breathing either alone or paired with trauma reduction exposure techniques significantly reduced PTSD symptoms compared with wait-list controls.¹⁴

Conclusion. Few controlled studies evaluated yoga for anxiety disorders, and all have significant methodologic limitations and/or poor methodology reporting. The diagnostic conditions treated and both yoga interventions and control conditions varied. However, these limited results are encouraging, particularly for treatment of obsessive-compulsive disorder (OCD). There is little information regarding safety or contraindications of yoga. Reported attrition rates were high in most studies, which may raise concerns about patient motivation and compliance.

Table 1

Evidence on the effectiveness of yoga for anxiety disorders

Exercise

The literature examining the relationship between exercise and depression is extensive, but much less has been published about exercise in patients with anxiety disorders (Table 2).^15-17 In a 10-week trial, Broocks and colleagues compared clomipramine, exercise (running), and placebo in 46 outpatients with panic disorder.¹⁵ Both exercise and clomipramine, 112.5 mg/d, significantly reduced panic symptoms compared with placebo, but clomipramine was more effective and faster-acting.

A more recent RCT compared group cognitive-behavioral therapy (GCBT) plus a home-based walking program vs GCBT and in 21 patients with panic disorder, generalized anxiety disorder (GAD), or social phobia.¹⁶ Compared with GCBT plus educational sessions, GCBT plus walking had a significant effect on self-reported depression, anxiety, and stress. Results differed by diagnosis; the most marked effects occurred in individuals with social phobia, whereas benefits for those with panic disorder or GAD were questionable.

Fifteen patients with OCD were recruited to participate in a 12-week, moderate-intensity aerobic exercise program added to their standard behavioral and/or pharmacologic treatment.¹⁷ Subjects demonstrated improvement in negative mood, anxiety, obsessions, and compulsions after each exercise session. Changes after each session persisted over the 12-week intervention, although the magnitude attenuated over the duration of the intervention.

Conclusion. Although initial results from small trials suggest exercise may help improve anxiety symptoms, further studies are needed to determine how to best use exercise training to treat anxious patients, specifically regarding dose-response relationship, differences in effectiveness between aerobic and resistance training, and the mechanisms by which exercise improves psychiatric symptoms.

Table 2

Exercise for anxiety: More research is needed

Bibliotherapy

Investigation of bibliotherapy for treatment of anxiety disorders has been limited (Table 3).^18-20 A 2009 RCT demonstrated that for 21 patients with mild-to-moderate social phobia, bibliotherapy—in the form of an 8-week self-directed CBT program with minimal therapist involvement—was superior to a wait-list control and induced clinically significant change in approximately one-third of patients.²⁰

Rapee et al randomly assigned 267 children age 6 to 12 with anxiety disorders to bibliotherapy that consisted of parents treating their children in the home with written materials, 9 sessions of GCBT, or a wait-list control condition.¹⁹ Bibliotherapy provided by parents demonstrated benefit compared with wait-listing but was not as efficacious as GCBT at post-treatment and 3-month follow-up.

Lidren and colleagues randomly assigned 36 adult patients with panic disorder to bibliotherapy, group therapy combined with bibliotherapy, or a waitlist.¹⁸ Both treatments were more effective than wait-listing in reducing the frequency of panic attacks, severity of physical panic symptoms, catastrophic cognitions, agoraphobic avoidance, and depression. Both interventions maintained their effects at 3-and 6-month follow-up and produced clinically significant change in most patients.

Conclusion. Some preliminary evidence supports the effectiveness of bibliotherapy for social anxiety disorder, childhood anxiety disorders, and panic disorder.

Table 3

Preliminary evidence supports bibliotherapy for select anxiety disorders

Dietary supplements

Many dietary and herbal supplements are purported to have therapeutic efficacy for anxiety symptoms. Because of inadequate FDA regulation of manufacturing and marketing of these agents, most of these supplements have not been tested on patients with anxiety disorders.²¹ Limited evidence supports the use of kava for GAD and inositol for panic disorder (Table 4).^22-28

Kava. Multiple double-blind RCTs found kava (Piper methysticum)—a plant indigenous to South Pacific islands—has effects greater than placebo and comparable to standard treatments for mild to moderately severe GAD. A Cochrane meta-analysis²² of 11 trials with 645 participants concluded that kava is effective for reducing GAD symptoms, with risks comparable to standard treatments for up to 6 months of use.

Case reports of kava-associated liver toxicity led to a marketing ban in Canada in 2000, followed shortly by Germany, Australia, and the United Kingdom. In 2002 the FDA issued a Consumer Advisory²⁹ discouraging kava use. Since then a flurry of research has looked for sources of possible toxicity, including individual sensitivities,²⁹ excessive dosing, use of toxic parts of the kava plant instead of the roots,^30,31 interactions with other hepatoactive substances, and non-water based extraction methods. RCTs demonstrating kava’s efficacy and safety were characterized by careful dosing supervision, use of standardized kava extracts, and avoidance of interactions with other hepatoactive medications or CAM treatments. Doses ≤300 mg/d are recommended.²²

RCTs that used the standardized acetone extract WS1490²³ found that women and younger adults show more positive effects from kava, and showed no liver toxicity when used for 1 to 24 weeks. A recent RCT that used kava extracts obtained via water-based methods showed kava had significant anxiolytic effects.²⁴ However, a study of liver toxicity reports found that water-based extractions, acetonic extractions, and ethanol extractions all have been associated with toxic hepatic reactions.³² Aqueous extraction does not guarantee safety, and the extraction solvent does not cause toxicity. A recent report of a severe liver reaction to the native drink by a tourist in Samoa³³ suggests that aqueous extractions from the root stock— the type of kava used by South Pacific islanders—also can be unsafe.

Conclusion. Multiple RCTs have found kava relatively safe and effective for treating anxiety symptoms. Caution is necessary, however, because of reports of liver toxicity associated with its use. Physician oversight and monitoring of kava use are appropriate.

Inositol. Evidence from RCTs suggests inositol, a natural isomer of glucose and a precursor in the phosphatidylinositol cycle, can significantly improve panic disorder symptoms.^25-28 In 1 trial, efficacy and side effects were comparable to fluvoxamine.²⁸ Effective doses ranged from 12 g/d to 18 g/d. Researchers tested inositol as monotherapy or augmentation to SSRIs for patients with mild-to-moderate OCD. In small double-blind crossover RCTs, inositol monotherapy significantly reduced Yale-Brown Obsessive Compulsive Scale scores compared with placebo²⁶ but inositol augmentation added nothing to the effects of SSRIs.²⁷

Conclusion. Inositol appears to be effective in improving symptoms of panic disorder. Its use for other anxiety disorders is unproven.

Table 4

Dietary supplements for anxiety disorders

Supervision is recommended

The evidence base for most CAM interventions commonly used for anxiety is relatively poor and recent systematic reviews found few methodologically rigorous studies. This has not, however, diminished CAM treatments’ popularity. Despite a paucity of high-quality studies regarding CAM for anxiety disorders, there is enough data supporting yoga, exercise, bibliotherapy, kava, and inositol to allow psychiatrists to collaborate with patients who wish to try these treatments. Advise patients that they may need physician supervision similar to that used with standard psychiatric treatments.

Related Resources

• National Center for Complementary and Alternative Medicine. http://nccam.nih.gov.
• The Journal of Alternative and Complementary Medicine. www.liebertonline.com/loi/acm.
• MedlinePlus: Complementary and Alternative Medicine. www.nlm.nih.gov/medlineplus/complementaryandalternativemedicine.html.

Drug Brand Names

• Amitriptyline • Elavil
• Chlordiazepoxide • Librium
• Clomipramine • Anafranil
• Diazepam • Valium
• Fluvoxamine • Luvox

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

The number of people with psychiatric disorders who use complementary and alternative medicine (CAM) is on the rise. In surveys of patients seeking psychiatric care, estimates of CAM use range from 8% to 57%; the most frequent uses are for depression and anxiety disorders. A population-based study in the United States found that 9% of respondents had anxiety attacks and 57% of these individuals had used CAM.¹ Similarly, in a Finnish population-based study (N=5,987) 35% of subjects reported some form of CAM use in the previous year; those with comorbid anxiety and depressive disorders used CAM most frequently.²

Unfortunately, a MEDLINE search shows that the number of studies examining psychotropic medications dwarfs the number of studies on even the most common CAM treatments used for psychiatric disorders. Far more patients with diagnosed mental disorders are studied in trials of standard treatments than CAM treatments. Because very few studies evaluate the cost-effectiveness of CAM treatments for psychiatric disorders, the risk-to-benefit ratio is difficult to calculate. Although several CAM treatments for depressive disorders have enough support to be considered options,³ CAM options for anxiety disorders are fewer and have less evidence of efficacy.

For these reasons, it is hard to recommend any CAM treatment as first line. Despite the relative lack of high quality research on CAM treatment outcomes, high rates of CAM use make it critical for clinicians to understand what treatments are available—or at least which treatments should be favored if patients are intent on trying them. We review the current research for yoga, exercise, bibliotherapy, and the dietary supplements kava and inositol for treating anxiety disorders and suggest those that warrant consideration for patients who do not respond, respond partially, or suffer from side effects from selective serotonin reuptake inhibitors (SSRIs) or benzodiazepines.

Limitations of CAM research

There are several limitations to the research literature on CAM approaches for anxiety disorders.⁴ First, there is a wide diversity of practices considered alternative or complementary and various ways in which these methods are applied across cultures. Some authors consider complementary medicines to be only herbal remedies, whereas others include individual therapies such as acupuncture, aromatherapy, herbal therapy, homeopathy, iridology, naturopathy, and reflexology.⁵ This article defines “alternative” treatments as those other than a form of psychotherapy or an FDA-approved medication that substitute for standard psychiatric treatment, and “complementary” approaches as those used to augment standard psychiatric treatments.

Anxiety and stress are ubiquitous, perhaps motivating interest in CAM options and prompting research on heterogeneous groups of individuals with poorly defined clinical syndromes or with isolated symptoms of anxiety or subjective distress. Few studies examine well-defined patient groups with diagnosed anxiety disorders. There are also multiple research design problems, including poorly specified treatments, poorly chosen placebos, and interpreting nonsignificant differences from established treatments as equivalence in underpowered studies.

The CAM treatments reviewed in this article have ≥2 randomized controlled trials (RCTs) that support their use for patients with diagnosed anxiety disorders, and ≥1 study that shows that the treatment can induce remission.

Yoga

In 2005 Kirkwood et al carried out the first systematic review of research evidence for the effectiveness of yoga in anxiety treatment.⁶ Of 19 studies identified, 4 RCTs and 1 nonrandomized trial met their inclusion criteria, which were an anxiety disorder diagnosis, use of yoga or yoga-based exercises alone, and anxiety rating scales used as outcome measures. Most found significant improvement in anxiety symptoms with yoga compared with placebo. Details of the 5 trials evaluated in Kirkwood’s review are summarized in Table 1.^7-11

Since the 2005 review, 3 additional studies of yoga and anxiety have been published, but none would meet Kirkwood’s inclusion criteria. One that evaluated a heterogeneous group of patients using an intervention with multiple components—only 1 of which was yoga—found the intervention significantly reduced anxiety scores.¹² A second study comparing yoga with relaxation in 131 patients with mild-to-moderate stress but no anxiety disorder diagnosis showed yoga was as effective as relaxation in improving anxiety symptoms as measured by the anxiety subscale of the State Trait Personality Inventory.¹³ In a study of 183 nonrandomized survivors of the 2004 southeast Asia tsunami with posttraumatic stress disorder (PTSD) symptoms, yoga-based breathing either alone or paired with trauma reduction exposure techniques significantly reduced PTSD symptoms compared with wait-list controls.¹⁴

Conclusion. Few controlled studies evaluated yoga for anxiety disorders, and all have significant methodologic limitations and/or poor methodology reporting. The diagnostic conditions treated and both yoga interventions and control conditions varied. However, these limited results are encouraging, particularly for treatment of obsessive-compulsive disorder (OCD). There is little information regarding safety or contraindications of yoga. Reported attrition rates were high in most studies, which may raise concerns about patient motivation and compliance.

Table 1

Evidence on the effectiveness of yoga for anxiety disorders

Exercise

The literature examining the relationship between exercise and depression is extensive, but much less has been published about exercise in patients with anxiety disorders (Table 2).^15-17 In a 10-week trial, Broocks and colleagues compared clomipramine, exercise (running), and placebo in 46 outpatients with panic disorder.¹⁵ Both exercise and clomipramine, 112.5 mg/d, significantly reduced panic symptoms compared with placebo, but clomipramine was more effective and faster-acting.

A more recent RCT compared group cognitive-behavioral therapy (GCBT) plus a home-based walking program vs GCBT and in 21 patients with panic disorder, generalized anxiety disorder (GAD), or social phobia.¹⁶ Compared with GCBT plus educational sessions, GCBT plus walking had a significant effect on self-reported depression, anxiety, and stress. Results differed by diagnosis; the most marked effects occurred in individuals with social phobia, whereas benefits for those with panic disorder or GAD were questionable.

Fifteen patients with OCD were recruited to participate in a 12-week, moderate-intensity aerobic exercise program added to their standard behavioral and/or pharmacologic treatment.¹⁷ Subjects demonstrated improvement in negative mood, anxiety, obsessions, and compulsions after each exercise session. Changes after each session persisted over the 12-week intervention, although the magnitude attenuated over the duration of the intervention.

Conclusion. Although initial results from small trials suggest exercise may help improve anxiety symptoms, further studies are needed to determine how to best use exercise training to treat anxious patients, specifically regarding dose-response relationship, differences in effectiveness between aerobic and resistance training, and the mechanisms by which exercise improves psychiatric symptoms.

Table 2

Exercise for anxiety: More research is needed

Bibliotherapy

Investigation of bibliotherapy for treatment of anxiety disorders has been limited (Table 3).^18-20 A 2009 RCT demonstrated that for 21 patients with mild-to-moderate social phobia, bibliotherapy—in the form of an 8-week self-directed CBT program with minimal therapist involvement—was superior to a wait-list control and induced clinically significant change in approximately one-third of patients.²⁰

Rapee et al randomly assigned 267 children age 6 to 12 with anxiety disorders to bibliotherapy that consisted of parents treating their children in the home with written materials, 9 sessions of GCBT, or a wait-list control condition.¹⁹ Bibliotherapy provided by parents demonstrated benefit compared with wait-listing but was not as efficacious as GCBT at post-treatment and 3-month follow-up.

Lidren and colleagues randomly assigned 36 adult patients with panic disorder to bibliotherapy, group therapy combined with bibliotherapy, or a waitlist.¹⁸ Both treatments were more effective than wait-listing in reducing the frequency of panic attacks, severity of physical panic symptoms, catastrophic cognitions, agoraphobic avoidance, and depression. Both interventions maintained their effects at 3-and 6-month follow-up and produced clinically significant change in most patients.

Conclusion. Some preliminary evidence supports the effectiveness of bibliotherapy for social anxiety disorder, childhood anxiety disorders, and panic disorder.

Table 3

Preliminary evidence supports bibliotherapy for select anxiety disorders

Dietary supplements

Many dietary and herbal supplements are purported to have therapeutic efficacy for anxiety symptoms. Because of inadequate FDA regulation of manufacturing and marketing of these agents, most of these supplements have not been tested on patients with anxiety disorders.²¹ Limited evidence supports the use of kava for GAD and inositol for panic disorder (Table 4).^22-28

Kava. Multiple double-blind RCTs found kava (Piper methysticum)—a plant indigenous to South Pacific islands—has effects greater than placebo and comparable to standard treatments for mild to moderately severe GAD. A Cochrane meta-analysis²² of 11 trials with 645 participants concluded that kava is effective for reducing GAD symptoms, with risks comparable to standard treatments for up to 6 months of use.

Case reports of kava-associated liver toxicity led to a marketing ban in Canada in 2000, followed shortly by Germany, Australia, and the United Kingdom. In 2002 the FDA issued a Consumer Advisory²⁹ discouraging kava use. Since then a flurry of research has looked for sources of possible toxicity, including individual sensitivities,²⁹ excessive dosing, use of toxic parts of the kava plant instead of the roots,^30,31 interactions with other hepatoactive substances, and non-water based extraction methods. RCTs demonstrating kava’s efficacy and safety were characterized by careful dosing supervision, use of standardized kava extracts, and avoidance of interactions with other hepatoactive medications or CAM treatments. Doses ≤300 mg/d are recommended.²²

RCTs that used the standardized acetone extract WS1490²³ found that women and younger adults show more positive effects from kava, and showed no liver toxicity when used for 1 to 24 weeks. A recent RCT that used kava extracts obtained via water-based methods showed kava had significant anxiolytic effects.²⁴ However, a study of liver toxicity reports found that water-based extractions, acetonic extractions, and ethanol extractions all have been associated with toxic hepatic reactions.³² Aqueous extraction does not guarantee safety, and the extraction solvent does not cause toxicity. A recent report of a severe liver reaction to the native drink by a tourist in Samoa³³ suggests that aqueous extractions from the root stock— the type of kava used by South Pacific islanders—also can be unsafe.

Conclusion. Multiple RCTs have found kava relatively safe and effective for treating anxiety symptoms. Caution is necessary, however, because of reports of liver toxicity associated with its use. Physician oversight and monitoring of kava use are appropriate.

Inositol. Evidence from RCTs suggests inositol, a natural isomer of glucose and a precursor in the phosphatidylinositol cycle, can significantly improve panic disorder symptoms.^25-28 In 1 trial, efficacy and side effects were comparable to fluvoxamine.²⁸ Effective doses ranged from 12 g/d to 18 g/d. Researchers tested inositol as monotherapy or augmentation to SSRIs for patients with mild-to-moderate OCD. In small double-blind crossover RCTs, inositol monotherapy significantly reduced Yale-Brown Obsessive Compulsive Scale scores compared with placebo²⁶ but inositol augmentation added nothing to the effects of SSRIs.²⁷

Conclusion. Inositol appears to be effective in improving symptoms of panic disorder. Its use for other anxiety disorders is unproven.

Table 4

Dietary supplements for anxiety disorders

Supervision is recommended

The evidence base for most CAM interventions commonly used for anxiety is relatively poor and recent systematic reviews found few methodologically rigorous studies. This has not, however, diminished CAM treatments’ popularity. Despite a paucity of high-quality studies regarding CAM for anxiety disorders, there is enough data supporting yoga, exercise, bibliotherapy, kava, and inositol to allow psychiatrists to collaborate with patients who wish to try these treatments. Advise patients that they may need physician supervision similar to that used with standard psychiatric treatments.

Related Resources

• National Center for Complementary and Alternative Medicine. http://nccam.nih.gov.
• The Journal of Alternative and Complementary Medicine. www.liebertonline.com/loi/acm.
• MedlinePlus: Complementary and Alternative Medicine. www.nlm.nih.gov/medlineplus/complementaryandalternativemedicine.html.

Drug Brand Names

• Amitriptyline • Elavil
• Chlordiazepoxide • Librium
• Clomipramine • Anafranil
• Diazepam • Valium
• Fluvoxamine • Luvox

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

[email protected]

As general pediatricians, you should feel confident in your ability to diagnose and manage dental trauma and emergencies. Bumped teeth that are not loose, bruised gums, and aphthous ulcers are dental emergencies that you can evaluate and treat in your office, for example.

In contrast, referral is warranted after trauma loosens a tooth, breaks it, or causes the tooth to come out (avulsion). In addition, a child who presents with extreme pain, an abscessed tooth, or a tooth pushed out of position should be referred to a specialist. Dental cellulitis and severe soft tissue injuries of the mouth are other reasons I typically see these children.

An avulsed permanent tooth should be replaced quickly, within seconds or minutes. The longer the tooth is out of the mouth, the poorer the prognosis. Do not handle the root surface, but do rinse lightly and quickly to remove foreign material. If it is impossible to reimplant the tooth immediately, instruct parents to store the tooth in milk or saline for transport to the dentist.

Once the child reaches a specialist, treatment may include reimplantation with a splint to stabilize the tooth, prescriptions for systemic antibiotics and oral antimicrobials, and pulp therapy. Inform parents that most displaced permanent teeth undergo pulpal necrosis and require initiation of root canal therapy 1 week after stabilization.

In contrast, primary teeth usually are not reimplanted. If a patient comes in with a “baby tooth” that has been knocked out, then just pass it on to the tooth fairy.

The good news is most tooth injuries are self-evident. Signs of trauma include discoloration and patient reports of pain associated with tooth movement, chewing, palpation, and/or sensitivity to hot or cold food or drinks.

If you see facial swelling, however, expand your differential diagnosis to include etiologies beyond the teeth or gingival tissue. Infections and allergic reactions, for example, also can cause substantial gingival swelling. Rule out ear infections, swollen lymph nodes, and strep throat and viral infections, because these can mimic dental concerns.

If a child presents after trauma with a fractured tooth, make sure to remove any tooth fragments before suturing nearby tissue, including lacerated lips. Hemorrhage control, cleansing, and suturing, as indicated, are important management tips for such soft tissue wounds. Antibiotics are recommended for all “through and through” lacerations.

Establish a working relationship with pediatric dentists and oral surgeons in your community. When a child requires immediate care, these specialists can provide telephone advice on how to handle the emergency and/or be a source of immediate referral for the patient.

A dentist never wants to see a child for the first time during a traumatic situation. Instead, each patient should see a dentist by age 1 to establish a dental home. A child who visits the dentist on a regular basis will become familiar with the provider and more comfortable in the event of a dental emergency. Education of parents on optimal oral health, prevention of problems, and appropriate dental development are other benefits of early, routine dental care.

I recommend the American Academy of Pediatrics Section on Pediatric Dentistry and Oral Health's new curriculum called Protecting All Children's Teeth (PACT): A Pediatric Oral Health Training Program (www.aap.org/oralhealth/pact.cfm

Some dental emergencies can be evaluated and treated in your office, according to Tonya Fuqua, D.D.S.

Source Courtesy Cook Children's Hospital

[email protected]

As general pediatricians, you should feel confident in your ability to diagnose and manage dental trauma and emergencies. Bumped teeth that are not loose, bruised gums, and aphthous ulcers are dental emergencies that you can evaluate and treat in your office, for example.

In contrast, referral is warranted after trauma loosens a tooth, breaks it, or causes the tooth to come out (avulsion). In addition, a child who presents with extreme pain, an abscessed tooth, or a tooth pushed out of position should be referred to a specialist. Dental cellulitis and severe soft tissue injuries of the mouth are other reasons I typically see these children.

An avulsed permanent tooth should be replaced quickly, within seconds or minutes. The longer the tooth is out of the mouth, the poorer the prognosis. Do not handle the root surface, but do rinse lightly and quickly to remove foreign material. If it is impossible to reimplant the tooth immediately, instruct parents to store the tooth in milk or saline for transport to the dentist.

Once the child reaches a specialist, treatment may include reimplantation with a splint to stabilize the tooth, prescriptions for systemic antibiotics and oral antimicrobials, and pulp therapy. Inform parents that most displaced permanent teeth undergo pulpal necrosis and require initiation of root canal therapy 1 week after stabilization.

In contrast, primary teeth usually are not reimplanted. If a patient comes in with a “baby tooth” that has been knocked out, then just pass it on to the tooth fairy.

The good news is most tooth injuries are self-evident. Signs of trauma include discoloration and patient reports of pain associated with tooth movement, chewing, palpation, and/or sensitivity to hot or cold food or drinks.

If you see facial swelling, however, expand your differential diagnosis to include etiologies beyond the teeth or gingival tissue. Infections and allergic reactions, for example, also can cause substantial gingival swelling. Rule out ear infections, swollen lymph nodes, and strep throat and viral infections, because these can mimic dental concerns.

If a child presents after trauma with a fractured tooth, make sure to remove any tooth fragments before suturing nearby tissue, including lacerated lips. Hemorrhage control, cleansing, and suturing, as indicated, are important management tips for such soft tissue wounds. Antibiotics are recommended for all “through and through” lacerations.

Establish a working relationship with pediatric dentists and oral surgeons in your community. When a child requires immediate care, these specialists can provide telephone advice on how to handle the emergency and/or be a source of immediate referral for the patient.

A dentist never wants to see a child for the first time during a traumatic situation. Instead, each patient should see a dentist by age 1 to establish a dental home. A child who visits the dentist on a regular basis will become familiar with the provider and more comfortable in the event of a dental emergency. Education of parents on optimal oral health, prevention of problems, and appropriate dental development are other benefits of early, routine dental care.

I recommend the American Academy of Pediatrics Section on Pediatric Dentistry and Oral Health's new curriculum called Protecting All Children's Teeth (PACT): A Pediatric Oral Health Training Program (www.aap.org/oralhealth/pact.cfm

Some dental emergencies can be evaluated and treated in your office, according to Tonya Fuqua, D.D.S.

Source Courtesy Cook Children's Hospital

[email protected]

As general pediatricians, you should feel confident in your ability to diagnose and manage dental trauma and emergencies. Bumped teeth that are not loose, bruised gums, and aphthous ulcers are dental emergencies that you can evaluate and treat in your office, for example.

In contrast, referral is warranted after trauma loosens a tooth, breaks it, or causes the tooth to come out (avulsion). In addition, a child who presents with extreme pain, an abscessed tooth, or a tooth pushed out of position should be referred to a specialist. Dental cellulitis and severe soft tissue injuries of the mouth are other reasons I typically see these children.

An avulsed permanent tooth should be replaced quickly, within seconds or minutes. The longer the tooth is out of the mouth, the poorer the prognosis. Do not handle the root surface, but do rinse lightly and quickly to remove foreign material. If it is impossible to reimplant the tooth immediately, instruct parents to store the tooth in milk or saline for transport to the dentist.

Once the child reaches a specialist, treatment may include reimplantation with a splint to stabilize the tooth, prescriptions for systemic antibiotics and oral antimicrobials, and pulp therapy. Inform parents that most displaced permanent teeth undergo pulpal necrosis and require initiation of root canal therapy 1 week after stabilization.

In contrast, primary teeth usually are not reimplanted. If a patient comes in with a “baby tooth” that has been knocked out, then just pass it on to the tooth fairy.

The good news is most tooth injuries are self-evident. Signs of trauma include discoloration and patient reports of pain associated with tooth movement, chewing, palpation, and/or sensitivity to hot or cold food or drinks.

If you see facial swelling, however, expand your differential diagnosis to include etiologies beyond the teeth or gingival tissue. Infections and allergic reactions, for example, also can cause substantial gingival swelling. Rule out ear infections, swollen lymph nodes, and strep throat and viral infections, because these can mimic dental concerns.

If a child presents after trauma with a fractured tooth, make sure to remove any tooth fragments before suturing nearby tissue, including lacerated lips. Hemorrhage control, cleansing, and suturing, as indicated, are important management tips for such soft tissue wounds. Antibiotics are recommended for all “through and through” lacerations.

Establish a working relationship with pediatric dentists and oral surgeons in your community. When a child requires immediate care, these specialists can provide telephone advice on how to handle the emergency and/or be a source of immediate referral for the patient.

A dentist never wants to see a child for the first time during a traumatic situation. Instead, each patient should see a dentist by age 1 to establish a dental home. A child who visits the dentist on a regular basis will become familiar with the provider and more comfortable in the event of a dental emergency. Education of parents on optimal oral health, prevention of problems, and appropriate dental development are other benefits of early, routine dental care.

I recommend the American Academy of Pediatrics Section on Pediatric Dentistry and Oral Health's new curriculum called Protecting All Children's Teeth (PACT): A Pediatric Oral Health Training Program (www.aap.org/oralhealth/pact.cfm

Some dental emergencies can be evaluated and treated in your office, according to Tonya Fuqua, D.D.S.

Source Courtesy Cook Children's Hospital