Diana Mahoney

CHICAGO — Providing family-centered, culturally sensitive care is a cornerstone of the American Academy of Pediatrics national medical home initiative, yet it is one that can be difficult to teach.

Recognizing that cultural sensitivity is a lesson best learned through exposure, the University of Puerto Rico, San Juan, has partnered with the United Way-Fondos Unidos de Puerto Rico to provide pediatric residents with firsthand exposure to the needs of the underserved and special-needs pediatric community.

Through the alliance, residents are assigned as volunteers to one of several United Way-affiliated agencies as part of their educational program, reported Maria del Rosario Gonzalez, M.D., in a poster presentation at a conference on Community Access to Child Health and Medical Home. Each resident performs a minimum of 100 hours of volunteer service throughout the residency program during protected time. The residents' orientation includes information on how to volunteer effectively, as well information about the culture of the population served by the given agency.

Since its inception in January of this year, the program has enrolled five nonprofit agencies, including a foster home for abused and neglected children, an agency serving patients with Down syndrome, a center for children with special health care needs, a foster home for pregnant adolescents, and an educational center for deaf children.

“The typical clinical setting limits residents' exposure to the needs of children in the community, and in particular those in high-risk populations,” said Dr. Gonzalez of the university. To better prepare residents to care for all members of the community, to become community leaders, and to assume an advocacy role in clinical settings for those at high risk, “we wanted to design an educational experience where residents would learn of their patients' needs by working with them in the patients' natural environment,” she said at the conference, sponsored by the American Academy of Pediatrics.

A second goal, said Dr. Gonzalez, “was to create awareness of the role of the nonprofit organizations and their volunteers in addressing the pressing needs of the underserved and high-risk groups, such as violence victims, HIV/AIDS patients, and children with special health care needs.”

Although the program is too young to have any hard outcome data, “the agencies have expressed their satisfaction with the experience,” said Dr. Gonzalez. “They are highly motivated and understand it fills a need in pediatricians' training.” For their part, the residents are also satisfied, she said. “They think it is enriching but hard and challenging.” In addition, she said, “the experience has provided the residents with an opportunity to explore their own attitudes toward volunteering and community service.”

The community alliance program is funded by an HRSA Bureau of Health Professions grant.

CHICAGO — Providing family-centered, culturally sensitive care is a cornerstone of the American Academy of Pediatrics national medical home initiative, yet it is one that can be difficult to teach.

Recognizing that cultural sensitivity is a lesson best learned through exposure, the University of Puerto Rico, San Juan, has partnered with the United Way-Fondos Unidos de Puerto Rico to provide pediatric residents with firsthand exposure to the needs of the underserved and special-needs pediatric community.

Through the alliance, residents are assigned as volunteers to one of several United Way-affiliated agencies as part of their educational program, reported Maria del Rosario Gonzalez, M.D., in a poster presentation at a conference on Community Access to Child Health and Medical Home. Each resident performs a minimum of 100 hours of volunteer service throughout the residency program during protected time. The residents' orientation includes information on how to volunteer effectively, as well information about the culture of the population served by the given agency.

Since its inception in January of this year, the program has enrolled five nonprofit agencies, including a foster home for abused and neglected children, an agency serving patients with Down syndrome, a center for children with special health care needs, a foster home for pregnant adolescents, and an educational center for deaf children.

“The typical clinical setting limits residents' exposure to the needs of children in the community, and in particular those in high-risk populations,” said Dr. Gonzalez of the university. To better prepare residents to care for all members of the community, to become community leaders, and to assume an advocacy role in clinical settings for those at high risk, “we wanted to design an educational experience where residents would learn of their patients' needs by working with them in the patients' natural environment,” she said at the conference, sponsored by the American Academy of Pediatrics.

A second goal, said Dr. Gonzalez, “was to create awareness of the role of the nonprofit organizations and their volunteers in addressing the pressing needs of the underserved and high-risk groups, such as violence victims, HIV/AIDS patients, and children with special health care needs.”

Although the program is too young to have any hard outcome data, “the agencies have expressed their satisfaction with the experience,” said Dr. Gonzalez. “They are highly motivated and understand it fills a need in pediatricians' training.” For their part, the residents are also satisfied, she said. “They think it is enriching but hard and challenging.” In addition, she said, “the experience has provided the residents with an opportunity to explore their own attitudes toward volunteering and community service.”

The community alliance program is funded by an HRSA Bureau of Health Professions grant.

CHICAGO — Providing family-centered, culturally sensitive care is a cornerstone of the American Academy of Pediatrics national medical home initiative, yet it is one that can be difficult to teach.

Recognizing that cultural sensitivity is a lesson best learned through exposure, the University of Puerto Rico, San Juan, has partnered with the United Way-Fondos Unidos de Puerto Rico to provide pediatric residents with firsthand exposure to the needs of the underserved and special-needs pediatric community.

Through the alliance, residents are assigned as volunteers to one of several United Way-affiliated agencies as part of their educational program, reported Maria del Rosario Gonzalez, M.D., in a poster presentation at a conference on Community Access to Child Health and Medical Home. Each resident performs a minimum of 100 hours of volunteer service throughout the residency program during protected time. The residents' orientation includes information on how to volunteer effectively, as well information about the culture of the population served by the given agency.

Since its inception in January of this year, the program has enrolled five nonprofit agencies, including a foster home for abused and neglected children, an agency serving patients with Down syndrome, a center for children with special health care needs, a foster home for pregnant adolescents, and an educational center for deaf children.

“The typical clinical setting limits residents' exposure to the needs of children in the community, and in particular those in high-risk populations,” said Dr. Gonzalez of the university. To better prepare residents to care for all members of the community, to become community leaders, and to assume an advocacy role in clinical settings for those at high risk, “we wanted to design an educational experience where residents would learn of their patients' needs by working with them in the patients' natural environment,” she said at the conference, sponsored by the American Academy of Pediatrics.

A second goal, said Dr. Gonzalez, “was to create awareness of the role of the nonprofit organizations and their volunteers in addressing the pressing needs of the underserved and high-risk groups, such as violence victims, HIV/AIDS patients, and children with special health care needs.”

Although the program is too young to have any hard outcome data, “the agencies have expressed their satisfaction with the experience,” said Dr. Gonzalez. “They are highly motivated and understand it fills a need in pediatricians' training.” For their part, the residents are also satisfied, she said. “They think it is enriching but hard and challenging.” In addition, she said, “the experience has provided the residents with an opportunity to explore their own attitudes toward volunteering and community service.”

The community alliance program is funded by an HRSA Bureau of Health Professions grant.

Rheumatoid arthritis patients suffering from interstitial lung disease may eventually have more targeted therapies, thanks to new evidence on the pathophysiology of the pulmonary condition.

Using computer-assisted image analysis, a team of investigators from the Mayo Clinic in Rochester, Minn., demonstrated an increased number of certain subtypes of T cells in the lung tissue of rheumatoid arthritis (RA) patients with interstitial pneumonitis (IP) compared with patients with the same pulmonary diagnosis who did not have RA.

The results support the long-held hypothesis that lung disease associated with RA might be T-cell driven, said Eric Matteson, M.D., one of the principal investigators.

“The fact that rheumatoid arthritis is thought to be a largely T-cell-driven disease has led to suspicions that T cells also play a major role in lung disease in RA patients.”

This study is the first to demonstrate the association through laboratory testing, he noted. “Up to this point, the possibility that extraarticular organ disease in RA is T-cell [mediated] has not been shown, other than studies of salivary glands in patients with Sjögren's disease,” he said.

The results also support the contention that rheumatoid interstitial lung disease is fundamentally different from other forms of the chronic, progressive pulmonary disorder, despite similarities in radiographic and histopathologic appearance. As such, the treatment approach “should likely be different as well,” Dr. Matteson said.

In their investigation, the Mayo Clinic researchers compared the prevalence of T-cell subtypes in lung biopsy specimens from 15 patients with rheumatoid IP with that observed in the specimens from 16 non-RA patients with idiopathic IP. Using immunohistochemical staining to enhance the T cells for microscopy and a high-resolution digital camera, the investigators acquired a total of 11,412 digital images of the stained specimens magnified 100 times (Arthritis Rheum. 2005;52:73-9).

Image analysis software helped quantify the stained T-cell markers relative to the total lung tissue. While conventional microscopy is an adequate technology for counting, it is poor for measuring areas, staining intensity, or distances—all of which are important for reducing sampling error and which can be achieved easily via computer-assisted analysis, said Dr. Matteson.

The analysis showed significantly more CD4 and CD3 cells among the rheumatoid arthritis patients, as well as a trend toward more CD8 cells. There was difference in T-cell prevalence between “usual” and “nonspecific” IP in RA patients, providing additional evidence that rheumatoid lung disease is distinctive.

In idiopathic manifestations, there are significant pathophysiologic and survival differences between usual and nonspecific classifications.

Those patients with RA-associated lung disease were more likely to be receiving current treatment with glucocorticosteroids at the time of lung biopsy than were patients with idiopathic lung disease, but these treatment differences did not explain the T-cell findings, said Dr. Matteson. “Steroids would be expected to reduce lymphoid infiltrates, which, if anything, would diminish differences in the number of cells positive for CD4 and other markers between the RA group and the non-RA group.”

If validated through additional studies, this finding could impact both the diagnosis and treatment of rheumatoid IP, which is estimated to affect 500,000 patients in the United States.

The image analysis technique employed by the investigators could be used to identify patients with RA-related lung disease early in the disease process. Rheumatoid arthritis that spreads beyond the joints involving the lungs is more likely to be fatal if not treated aggressively in its early stages, Dr. Matteson said.

The findings also may help guide the use and/or development of more drugs that specifically target the involved immune activity, he noted.

“There is a certain nihilism about treating putatively immune mediated interstitial lung disease in idiopathic cases as well as in inflammatory rheumatic diseases, because so many patients seem to respond poorly to therapy, which is relatively nonspecific,” said Dr. Matteson.

The conventional treatment approaches include high-dose glucocorticosteroids, cyclophosphamide, and cyclosporine, although there are no data demonstrating the efficacy of these agents on lung function or survival.

“T-cell directed therapies such as the anti-CD4 therapies under development may be more appropriate for managing rheumatoid lung disease,” Dr. Matteson said.

“T cells also govern, and are governed by, the cytokine milieu in rheumatoid arthritis, including tumor necrosis factor. These therapies could also be helpful, although emerging reports of TNF-related pulmonary toxicity indicate there is still much to be learned before these approaches are considered,” he stated.

In addition to T-cell involvement, the B cell may be of central importance to lung disease, and may also provide a potential target. The Mayo team is actively investigating the possibility of B-cell involvement, as well as antigen development and processing in the rheumatic lung.

Rheumatoid arthritis patients suffering from interstitial lung disease may eventually have more targeted therapies, thanks to new evidence on the pathophysiology of the pulmonary condition.

Using computer-assisted image analysis, a team of investigators from the Mayo Clinic in Rochester, Minn., demonstrated an increased number of certain subtypes of T cells in the lung tissue of rheumatoid arthritis (RA) patients with interstitial pneumonitis (IP) compared with patients with the same pulmonary diagnosis who did not have RA.

The results support the long-held hypothesis that lung disease associated with RA might be T-cell driven, said Eric Matteson, M.D., one of the principal investigators.

“The fact that rheumatoid arthritis is thought to be a largely T-cell-driven disease has led to suspicions that T cells also play a major role in lung disease in RA patients.”

This study is the first to demonstrate the association through laboratory testing, he noted. “Up to this point, the possibility that extraarticular organ disease in RA is T-cell [mediated] has not been shown, other than studies of salivary glands in patients with Sjögren's disease,” he said.

The results also support the contention that rheumatoid interstitial lung disease is fundamentally different from other forms of the chronic, progressive pulmonary disorder, despite similarities in radiographic and histopathologic appearance. As such, the treatment approach “should likely be different as well,” Dr. Matteson said.

In their investigation, the Mayo Clinic researchers compared the prevalence of T-cell subtypes in lung biopsy specimens from 15 patients with rheumatoid IP with that observed in the specimens from 16 non-RA patients with idiopathic IP. Using immunohistochemical staining to enhance the T cells for microscopy and a high-resolution digital camera, the investigators acquired a total of 11,412 digital images of the stained specimens magnified 100 times (Arthritis Rheum. 2005;52:73-9).

Image analysis software helped quantify the stained T-cell markers relative to the total lung tissue. While conventional microscopy is an adequate technology for counting, it is poor for measuring areas, staining intensity, or distances—all of which are important for reducing sampling error and which can be achieved easily via computer-assisted analysis, said Dr. Matteson.

The analysis showed significantly more CD4 and CD3 cells among the rheumatoid arthritis patients, as well as a trend toward more CD8 cells. There was difference in T-cell prevalence between “usual” and “nonspecific” IP in RA patients, providing additional evidence that rheumatoid lung disease is distinctive.

In idiopathic manifestations, there are significant pathophysiologic and survival differences between usual and nonspecific classifications.

Those patients with RA-associated lung disease were more likely to be receiving current treatment with glucocorticosteroids at the time of lung biopsy than were patients with idiopathic lung disease, but these treatment differences did not explain the T-cell findings, said Dr. Matteson. “Steroids would be expected to reduce lymphoid infiltrates, which, if anything, would diminish differences in the number of cells positive for CD4 and other markers between the RA group and the non-RA group.”

If validated through additional studies, this finding could impact both the diagnosis and treatment of rheumatoid IP, which is estimated to affect 500,000 patients in the United States.

The image analysis technique employed by the investigators could be used to identify patients with RA-related lung disease early in the disease process. Rheumatoid arthritis that spreads beyond the joints involving the lungs is more likely to be fatal if not treated aggressively in its early stages, Dr. Matteson said.

The findings also may help guide the use and/or development of more drugs that specifically target the involved immune activity, he noted.

“There is a certain nihilism about treating putatively immune mediated interstitial lung disease in idiopathic cases as well as in inflammatory rheumatic diseases, because so many patients seem to respond poorly to therapy, which is relatively nonspecific,” said Dr. Matteson.

The conventional treatment approaches include high-dose glucocorticosteroids, cyclophosphamide, and cyclosporine, although there are no data demonstrating the efficacy of these agents on lung function or survival.

“T-cell directed therapies such as the anti-CD4 therapies under development may be more appropriate for managing rheumatoid lung disease,” Dr. Matteson said.

“T cells also govern, and are governed by, the cytokine milieu in rheumatoid arthritis, including tumor necrosis factor. These therapies could also be helpful, although emerging reports of TNF-related pulmonary toxicity indicate there is still much to be learned before these approaches are considered,” he stated.

In addition to T-cell involvement, the B cell may be of central importance to lung disease, and may also provide a potential target. The Mayo team is actively investigating the possibility of B-cell involvement, as well as antigen development and processing in the rheumatic lung.

Rheumatoid arthritis patients suffering from interstitial lung disease may eventually have more targeted therapies, thanks to new evidence on the pathophysiology of the pulmonary condition.

Using computer-assisted image analysis, a team of investigators from the Mayo Clinic in Rochester, Minn., demonstrated an increased number of certain subtypes of T cells in the lung tissue of rheumatoid arthritis (RA) patients with interstitial pneumonitis (IP) compared with patients with the same pulmonary diagnosis who did not have RA.

The results support the long-held hypothesis that lung disease associated with RA might be T-cell driven, said Eric Matteson, M.D., one of the principal investigators.

“The fact that rheumatoid arthritis is thought to be a largely T-cell-driven disease has led to suspicions that T cells also play a major role in lung disease in RA patients.”

This study is the first to demonstrate the association through laboratory testing, he noted. “Up to this point, the possibility that extraarticular organ disease in RA is T-cell [mediated] has not been shown, other than studies of salivary glands in patients with Sjögren's disease,” he said.

The results also support the contention that rheumatoid interstitial lung disease is fundamentally different from other forms of the chronic, progressive pulmonary disorder, despite similarities in radiographic and histopathologic appearance. As such, the treatment approach “should likely be different as well,” Dr. Matteson said.

In their investigation, the Mayo Clinic researchers compared the prevalence of T-cell subtypes in lung biopsy specimens from 15 patients with rheumatoid IP with that observed in the specimens from 16 non-RA patients with idiopathic IP. Using immunohistochemical staining to enhance the T cells for microscopy and a high-resolution digital camera, the investigators acquired a total of 11,412 digital images of the stained specimens magnified 100 times (Arthritis Rheum. 2005;52:73-9).

Image analysis software helped quantify the stained T-cell markers relative to the total lung tissue. While conventional microscopy is an adequate technology for counting, it is poor for measuring areas, staining intensity, or distances—all of which are important for reducing sampling error and which can be achieved easily via computer-assisted analysis, said Dr. Matteson.

The analysis showed significantly more CD4 and CD3 cells among the rheumatoid arthritis patients, as well as a trend toward more CD8 cells. There was difference in T-cell prevalence between “usual” and “nonspecific” IP in RA patients, providing additional evidence that rheumatoid lung disease is distinctive.

In idiopathic manifestations, there are significant pathophysiologic and survival differences between usual and nonspecific classifications.

Those patients with RA-associated lung disease were more likely to be receiving current treatment with glucocorticosteroids at the time of lung biopsy than were patients with idiopathic lung disease, but these treatment differences did not explain the T-cell findings, said Dr. Matteson. “Steroids would be expected to reduce lymphoid infiltrates, which, if anything, would diminish differences in the number of cells positive for CD4 and other markers between the RA group and the non-RA group.”

If validated through additional studies, this finding could impact both the diagnosis and treatment of rheumatoid IP, which is estimated to affect 500,000 patients in the United States.

The image analysis technique employed by the investigators could be used to identify patients with RA-related lung disease early in the disease process. Rheumatoid arthritis that spreads beyond the joints involving the lungs is more likely to be fatal if not treated aggressively in its early stages, Dr. Matteson said.

The findings also may help guide the use and/or development of more drugs that specifically target the involved immune activity, he noted.

“There is a certain nihilism about treating putatively immune mediated interstitial lung disease in idiopathic cases as well as in inflammatory rheumatic diseases, because so many patients seem to respond poorly to therapy, which is relatively nonspecific,” said Dr. Matteson.

The conventional treatment approaches include high-dose glucocorticosteroids, cyclophosphamide, and cyclosporine, although there are no data demonstrating the efficacy of these agents on lung function or survival.

“T-cell directed therapies such as the anti-CD4 therapies under development may be more appropriate for managing rheumatoid lung disease,” Dr. Matteson said.

“T cells also govern, and are governed by, the cytokine milieu in rheumatoid arthritis, including tumor necrosis factor. These therapies could also be helpful, although emerging reports of TNF-related pulmonary toxicity indicate there is still much to be learned before these approaches are considered,” he stated.

In addition to T-cell involvement, the B cell may be of central importance to lung disease, and may also provide a potential target. The Mayo team is actively investigating the possibility of B-cell involvement, as well as antigen development and processing in the rheumatic lung.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder. In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their dosage and stop medication before conception. If symptoms emerge during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, she said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation. Valproic acid, on the other hand, is associated with a 3%-5% risk of a neural tube defect and an 8.9% risk for all anomalies vs. a baseline rate of 2%-4%.

The risk of bipolar relapse in the postpartum period is high, as is the risk for postpartum psychosis. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said. “The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and others have suggested 24-48 hours post partum. In any case, Dr. Viguera said, “the postpartum treatment plan should be addressed in advance.”

Drugs Often Used in Pregnant Patients

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Studies have shown the teratogenicity rates are much lower than previously reported. Common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. They are linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as first-line therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in babies exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in babies who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic is often used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been associated with significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety.

Strategies for minimizing the risks associated with these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. Women taking anticonvulsants, in particular, should take 4 mg of supplemental folic acid per day from preconception through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16-18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted. Both maternal and fetal serum drug levels should be monitored regularly.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder. In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their dosage and stop medication before conception. If symptoms emerge during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, she said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation. Valproic acid, on the other hand, is associated with a 3%-5% risk of a neural tube defect and an 8.9% risk for all anomalies vs. a baseline rate of 2%-4%.

The risk of bipolar relapse in the postpartum period is high, as is the risk for postpartum psychosis. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said. “The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and others have suggested 24-48 hours post partum. In any case, Dr. Viguera said, “the postpartum treatment plan should be addressed in advance.”

Drugs Often Used in Pregnant Patients

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Studies have shown the teratogenicity rates are much lower than previously reported. Common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. They are linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as first-line therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in babies exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in babies who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic is often used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been associated with significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety.

Strategies for minimizing the risks associated with these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. Women taking anticonvulsants, in particular, should take 4 mg of supplemental folic acid per day from preconception through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16-18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted. Both maternal and fetal serum drug levels should be monitored regularly.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder. In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their dosage and stop medication before conception. If symptoms emerge during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, she said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation. Valproic acid, on the other hand, is associated with a 3%-5% risk of a neural tube defect and an 8.9% risk for all anomalies vs. a baseline rate of 2%-4%.

The risk of bipolar relapse in the postpartum period is high, as is the risk for postpartum psychosis. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said. “The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and others have suggested 24-48 hours post partum. In any case, Dr. Viguera said, “the postpartum treatment plan should be addressed in advance.”

Drugs Often Used in Pregnant Patients

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Studies have shown the teratogenicity rates are much lower than previously reported. Common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. They are linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as first-line therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in babies exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in babies who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic is often used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been associated with significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety.

Strategies for minimizing the risks associated with these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. Women taking anticonvulsants, in particular, should take 4 mg of supplemental folic acid per day from preconception through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16-18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted. Both maternal and fetal serum drug levels should be monitored regularly.

Childhood depression has grabbed a lot of headlines recently, with major news media devoting ample space to the question, “Why are so many kids depressed, and what are we doing about it?”

And few if any of these headlines have been bigger or louder than the recent ones addressing the possible association between suicide risk and antidepressant use in children and adolescents, and the Food and Drug Administration's directive that a black box label be placed on selective serotonin reuptake inhibitors warning of this possible association.

The news behind these headlines has forced child and adolescent health care providers to ask themselves not only what is being done about depression in kids, but also, in light of the potential dangers of drug therapy, what can be done differently? For many children, the answer may lie with their parents' depression.

Studies have shown that parents with untreated depression are likely to have depressed children. “The odds of a child suffering from depression are at 25% if one parent suffers from depression. If both parents suffer from depression, the child has a 75%,” said David Fassler, M.D., of the University of Vermont, Burlington.

Children of depressed parents are also at higher risk for substance abuse, antisocial behavior, and a cascade of problems associated with attachment, anxiety, physical health, academic performance, self-esteem, aggression, behavior, and language (Psychol. Bull. 1990;108:50-76).

The problems can begin in infancy and grow along with the child. The younger a child is when the parent becomes depressed, the greater the impact will be, said Dr. Fassler, who is also coauthor of the book “'Help Me, I'm Sad': Recognizing, Treating, and Preventing Childhood and Adolescent Depression” (New York: Little, Brown and Co., 2003).

Several studies have shown that depressed mothers have trouble bonding with their newborns, are less sensitive than nondepressed mothers to their babies' needs, and are less consistent in how they respond to their babies' behavior. The behavior of their babies—listless, unhappy, hard to comfort—reflects those deficits, as does defiant, out-of-control behavior in a toddler.

Pair the difficulty dealing with their children with depressed parents' irritability, fatigue, pessimism, and social/emotional withdrawal, and the cycle is perpetuated into adolescence, where it manifests as poor academic performance, lack of motivation, social withdrawal, a sense of hopelessness and, potentially, suicidal thinking.

Although parental depression is not the only risk factor for depression in children, it is a major—and changeable—one. “There are certain steps you can take to reduce the risks for a child with a family history of mental illness,” Dr. Fassler said. These include monitoring the child for possible signs and symptoms of depression, as well as modifying the environmental contributors, which sometimes includes treating the parents' depression.

The first step toward effective intervention is to develop a treatment plan specific to the child and the family. Often, this might include individual and family therapy, school involvement, and, if necessary, adjunctive medication. Medication should only be used as part of a comprehensive, individualized treatment plan,” Dr. Fassler said.

Applying a family-based approach to the prevention of depressive symptoms does work. In a 2003 study, William Beardslee, M.D., head of psychiatry at Children's Hospital Boston, and his colleagues at the affiliated Judge Baker Children's Center, tested the effectiveness of two cognitive, psychoeducational, preventive interventions in children of depressed parents (see related story).

Preliminary results from the first-of-its-kind longitudinal primary prevention study of healthy kids at risk for psychopathology showed that the interventions, which addressed parental depression, resulted in a significant reduction in risk factors and increase in protective factors in the participating families over more than 2 years.

The case for preventive intervention among depressed families is a strong one. Several studies on children who were depressed before puberty show that they had a higher rate of antisocial behavior, anxiety, and major depression as adults than adults who experienced their first depressive episode as teens. Often, these children have little understanding of depression and feel like outsiders in their own world.

On the other hand, children who receive support and reassurance that their depression has a name and is treatable—and that their parents' depression is not a reflection on them but an illness to be overcome—are less likely to get caught in the intractable cycle and become depressed parents themselves.

Models Build Resilience in Children of Parents With Depression

Helping children understand a parent's mood disorder through open, honest communication fosters resiliency in those who might otherwise succumb to mental illness, according to Dr. Beardslee.

For children living in homes with depressed parents, promoting resilience through communication is the central component of a family-based intervention developed by Dr. Beardslee and his colleagues at the Judge Baker Children's Center in Boston.

Based on studies they conducted in the 1980s, Dr. Beardslee has identified core characteristics of resilient youth: a desire to accomplish developmental tasks outside the home, such as doing well in school or in sports; a commitment to relationships with friends, siblings, and parents; and an understanding that they are not to blame for a parent's illness.

Giving depressed parents the tools to build resilience in their children is central to the Prevention Intervention Project. The manualized, stepwise therapeutic strategy teaches parents to encourage children to pursue interests, relationships, and activities outside the home and to talk about the illness in a productive way.

The intervention is designed for use by physicians, school counselors, nurses, and mental health professionals.

Two models—one lecture based, the other clinician led—have been tested with promising results. In the lecture-based model, parents attend two group meetings without their children. In the clinician-led version, parents and children attend a series of 6-11 meetings facilitated by a clinician, as well as a family meeting led by the parents during which the illness is discussed.

Participants in both interventions receive information about mood disorders, risk, and resilience, and both interventions focus on removing misunderstanding, guilt, and blame.

In the clinician-led intervention, cognitive information is linked specifically to the individual's life and family experiences, while the lecture intervention presents that information in a group format with opportunity for discussion. Unlike in the clinician model, children of families receiving the lecture intervention are not seen directly; parents are encouraged to talk with their children.

In an examination of the efficacy of the programs at 1 year and 2 ½ years post intervention among 100 families randomly assigned to one of the two intervention models, parents in both conditions reported significant change in child-related behaviors and attitudes, and the amount of change increased over time. Children in both conditions reported increased understanding of parental illness, and internalizing scores for all of the children decreased (Pediatrics 2003;112:e119-31).

Although more change was seen in the clinician-led group, the long-standing positive effects of both interventions suggest that interventions built around family involvement, even if brief, “translate into significant mental health gains for children and families,” Dr. Beardslee said.

Perspective

By CARL C. BELL, M.D., president and CEO of Community Mental Health Council Inc. Chicago, and director of public and community psychiatry, University of Illinois at Chicago.

We live in a society that believes in “better living through chemistry.” Fortunately, there are those who rail against the trend of taking a pill for everything that ails us. But in the treatment of mental illness, hard work is critical to helping patients achieve health and well-being.

In my research, I have uncovered several key principles necessary to cultivate resilience and resistance in individuals so they won't need pills to manage clinical illness. We need to:

▸ Create a social fabric around individuals.

▸ Establish systems that promote interpersonal connectedness as a way to facilitate health behavior change.

▸ Develop infrastructures that promote social skills, personal value, and empowerment.

▸ Provide children with an adult protective shield to increase protective factors and decrease risk factors.

▸ Strive to minimize the experience and impact of trauma.

▸ Support quality psychosocial research at the level we have been supporting biomedical research.

Validated programs that incorporate these principles, such as the Preventive Intervention Project, need to be aggressively marketed. For example, people are more hyped about preventing maternal transmission of HIV than preventing parental transmission of depression because of the availability of clear-cut, proven, hard biologic interventions for HIV. To encourage a paradigm shift in mental illness, science needs to show equally strong evidence for psychosocial interventions, along with a strong advocacy campaign to convince people that psychosocial interventions are as valuable as biological ones.

Another obstacle is our couch-potato society's shortsighted preoccupation with how long something takes.

Some would argue that 6-11 manualized, evidence-based sessions aimed at helping a child keep from getting depressed is a significant time commitment, but consider the possible depression-related outcomes without such efforts: school failure, substance abuse, hopelessness, and suicide attempts. How can an individual or a society not make such a time investment?

It boils down to paying now or paying much, much more later, akin to the old Chinese proverb: “You are a fool if you wait until you are thirsty before you start digging your well.

Childhood depression has grabbed a lot of headlines recently, with major news media devoting ample space to the question, “Why are so many kids depressed, and what are we doing about it?”

And few if any of these headlines have been bigger or louder than the recent ones addressing the possible association between suicide risk and antidepressant use in children and adolescents, and the Food and Drug Administration's directive that a black box label be placed on selective serotonin reuptake inhibitors warning of this possible association.

The news behind these headlines has forced child and adolescent health care providers to ask themselves not only what is being done about depression in kids, but also, in light of the potential dangers of drug therapy, what can be done differently? For many children, the answer may lie with their parents' depression.

Studies have shown that parents with untreated depression are likely to have depressed children. “The odds of a child suffering from depression are at 25% if one parent suffers from depression. If both parents suffer from depression, the child has a 75%,” said David Fassler, M.D., of the University of Vermont, Burlington.

Children of depressed parents are also at higher risk for substance abuse, antisocial behavior, and a cascade of problems associated with attachment, anxiety, physical health, academic performance, self-esteem, aggression, behavior, and language (Psychol. Bull. 1990;108:50-76).

The problems can begin in infancy and grow along with the child. The younger a child is when the parent becomes depressed, the greater the impact will be, said Dr. Fassler, who is also coauthor of the book “'Help Me, I'm Sad': Recognizing, Treating, and Preventing Childhood and Adolescent Depression” (New York: Little, Brown and Co., 2003).

Several studies have shown that depressed mothers have trouble bonding with their newborns, are less sensitive than nondepressed mothers to their babies' needs, and are less consistent in how they respond to their babies' behavior. The behavior of their babies—listless, unhappy, hard to comfort—reflects those deficits, as does defiant, out-of-control behavior in a toddler.

Pair the difficulty dealing with their children with depressed parents' irritability, fatigue, pessimism, and social/emotional withdrawal, and the cycle is perpetuated into adolescence, where it manifests as poor academic performance, lack of motivation, social withdrawal, a sense of hopelessness and, potentially, suicidal thinking.

Although parental depression is not the only risk factor for depression in children, it is a major—and changeable—one. “There are certain steps you can take to reduce the risks for a child with a family history of mental illness,” Dr. Fassler said. These include monitoring the child for possible signs and symptoms of depression, as well as modifying the environmental contributors, which sometimes includes treating the parents' depression.

The first step toward effective intervention is to develop a treatment plan specific to the child and the family. Often, this might include individual and family therapy, school involvement, and, if necessary, adjunctive medication. Medication should only be used as part of a comprehensive, individualized treatment plan,” Dr. Fassler said.

Applying a family-based approach to the prevention of depressive symptoms does work. In a 2003 study, William Beardslee, M.D., head of psychiatry at Children's Hospital Boston, and his colleagues at the affiliated Judge Baker Children's Center, tested the effectiveness of two cognitive, psychoeducational, preventive interventions in children of depressed parents (see related story).

Preliminary results from the first-of-its-kind longitudinal primary prevention study of healthy kids at risk for psychopathology showed that the interventions, which addressed parental depression, resulted in a significant reduction in risk factors and increase in protective factors in the participating families over more than 2 years.

The case for preventive intervention among depressed families is a strong one. Several studies on children who were depressed before puberty show that they had a higher rate of antisocial behavior, anxiety, and major depression as adults than adults who experienced their first depressive episode as teens. Often, these children have little understanding of depression and feel like outsiders in their own world.

On the other hand, children who receive support and reassurance that their depression has a name and is treatable—and that their parents' depression is not a reflection on them but an illness to be overcome—are less likely to get caught in the intractable cycle and become depressed parents themselves.

Models Build Resilience in Children of Parents With Depression

Helping children understand a parent's mood disorder through open, honest communication fosters resiliency in those who might otherwise succumb to mental illness, according to Dr. Beardslee.

For children living in homes with depressed parents, promoting resilience through communication is the central component of a family-based intervention developed by Dr. Beardslee and his colleagues at the Judge Baker Children's Center in Boston.

Based on studies they conducted in the 1980s, Dr. Beardslee has identified core characteristics of resilient youth: a desire to accomplish developmental tasks outside the home, such as doing well in school or in sports; a commitment to relationships with friends, siblings, and parents; and an understanding that they are not to blame for a parent's illness.

Giving depressed parents the tools to build resilience in their children is central to the Prevention Intervention Project. The manualized, stepwise therapeutic strategy teaches parents to encourage children to pursue interests, relationships, and activities outside the home and to talk about the illness in a productive way.

The intervention is designed for use by physicians, school counselors, nurses, and mental health professionals.

Two models—one lecture based, the other clinician led—have been tested with promising results. In the lecture-based model, parents attend two group meetings without their children. In the clinician-led version, parents and children attend a series of 6-11 meetings facilitated by a clinician, as well as a family meeting led by the parents during which the illness is discussed.

Participants in both interventions receive information about mood disorders, risk, and resilience, and both interventions focus on removing misunderstanding, guilt, and blame.

In the clinician-led intervention, cognitive information is linked specifically to the individual's life and family experiences, while the lecture intervention presents that information in a group format with opportunity for discussion. Unlike in the clinician model, children of families receiving the lecture intervention are not seen directly; parents are encouraged to talk with their children.

In an examination of the efficacy of the programs at 1 year and 2 ½ years post intervention among 100 families randomly assigned to one of the two intervention models, parents in both conditions reported significant change in child-related behaviors and attitudes, and the amount of change increased over time. Children in both conditions reported increased understanding of parental illness, and internalizing scores for all of the children decreased (Pediatrics 2003;112:e119-31).

Although more change was seen in the clinician-led group, the long-standing positive effects of both interventions suggest that interventions built around family involvement, even if brief, “translate into significant mental health gains for children and families,” Dr. Beardslee said.

Perspective

By CARL C. BELL, M.D., president and CEO of Community Mental Health Council Inc. Chicago, and director of public and community psychiatry, University of Illinois at Chicago.

We live in a society that believes in “better living through chemistry.” Fortunately, there are those who rail against the trend of taking a pill for everything that ails us. But in the treatment of mental illness, hard work is critical to helping patients achieve health and well-being.

In my research, I have uncovered several key principles necessary to cultivate resilience and resistance in individuals so they won't need pills to manage clinical illness. We need to:

▸ Create a social fabric around individuals.

▸ Establish systems that promote interpersonal connectedness as a way to facilitate health behavior change.

▸ Develop infrastructures that promote social skills, personal value, and empowerment.

▸ Provide children with an adult protective shield to increase protective factors and decrease risk factors.

▸ Strive to minimize the experience and impact of trauma.

▸ Support quality psychosocial research at the level we have been supporting biomedical research.

Validated programs that incorporate these principles, such as the Preventive Intervention Project, need to be aggressively marketed. For example, people are more hyped about preventing maternal transmission of HIV than preventing parental transmission of depression because of the availability of clear-cut, proven, hard biologic interventions for HIV. To encourage a paradigm shift in mental illness, science needs to show equally strong evidence for psychosocial interventions, along with a strong advocacy campaign to convince people that psychosocial interventions are as valuable as biological ones.

Another obstacle is our couch-potato society's shortsighted preoccupation with how long something takes.

Some would argue that 6-11 manualized, evidence-based sessions aimed at helping a child keep from getting depressed is a significant time commitment, but consider the possible depression-related outcomes without such efforts: school failure, substance abuse, hopelessness, and suicide attempts. How can an individual or a society not make such a time investment?

It boils down to paying now or paying much, much more later, akin to the old Chinese proverb: “You are a fool if you wait until you are thirsty before you start digging your well.

Childhood depression has grabbed a lot of headlines recently, with major news media devoting ample space to the question, “Why are so many kids depressed, and what are we doing about it?”

And few if any of these headlines have been bigger or louder than the recent ones addressing the possible association between suicide risk and antidepressant use in children and adolescents, and the Food and Drug Administration's directive that a black box label be placed on selective serotonin reuptake inhibitors warning of this possible association.

The news behind these headlines has forced child and adolescent health care providers to ask themselves not only what is being done about depression in kids, but also, in light of the potential dangers of drug therapy, what can be done differently? For many children, the answer may lie with their parents' depression.

Studies have shown that parents with untreated depression are likely to have depressed children. “The odds of a child suffering from depression are at 25% if one parent suffers from depression. If both parents suffer from depression, the child has a 75%,” said David Fassler, M.D., of the University of Vermont, Burlington.

Children of depressed parents are also at higher risk for substance abuse, antisocial behavior, and a cascade of problems associated with attachment, anxiety, physical health, academic performance, self-esteem, aggression, behavior, and language (Psychol. Bull. 1990;108:50-76).

The problems can begin in infancy and grow along with the child. The younger a child is when the parent becomes depressed, the greater the impact will be, said Dr. Fassler, who is also coauthor of the book “'Help Me, I'm Sad': Recognizing, Treating, and Preventing Childhood and Adolescent Depression” (New York: Little, Brown and Co., 2003).

Several studies have shown that depressed mothers have trouble bonding with their newborns, are less sensitive than nondepressed mothers to their babies' needs, and are less consistent in how they respond to their babies' behavior. The behavior of their babies—listless, unhappy, hard to comfort—reflects those deficits, as does defiant, out-of-control behavior in a toddler.

Pair the difficulty dealing with their children with depressed parents' irritability, fatigue, pessimism, and social/emotional withdrawal, and the cycle is perpetuated into adolescence, where it manifests as poor academic performance, lack of motivation, social withdrawal, a sense of hopelessness and, potentially, suicidal thinking.

Although parental depression is not the only risk factor for depression in children, it is a major—and changeable—one. “There are certain steps you can take to reduce the risks for a child with a family history of mental illness,” Dr. Fassler said. These include monitoring the child for possible signs and symptoms of depression, as well as modifying the environmental contributors, which sometimes includes treating the parents' depression.

The first step toward effective intervention is to develop a treatment plan specific to the child and the family. Often, this might include individual and family therapy, school involvement, and, if necessary, adjunctive medication. Medication should only be used as part of a comprehensive, individualized treatment plan,” Dr. Fassler said.

Applying a family-based approach to the prevention of depressive symptoms does work. In a 2003 study, William Beardslee, M.D., head of psychiatry at Children's Hospital Boston, and his colleagues at the affiliated Judge Baker Children's Center, tested the effectiveness of two cognitive, psychoeducational, preventive interventions in children of depressed parents (see related story).

Preliminary results from the first-of-its-kind longitudinal primary prevention study of healthy kids at risk for psychopathology showed that the interventions, which addressed parental depression, resulted in a significant reduction in risk factors and increase in protective factors in the participating families over more than 2 years.

The case for preventive intervention among depressed families is a strong one. Several studies on children who were depressed before puberty show that they had a higher rate of antisocial behavior, anxiety, and major depression as adults than adults who experienced their first depressive episode as teens. Often, these children have little understanding of depression and feel like outsiders in their own world.

On the other hand, children who receive support and reassurance that their depression has a name and is treatable—and that their parents' depression is not a reflection on them but an illness to be overcome—are less likely to get caught in the intractable cycle and become depressed parents themselves.

Models Build Resilience in Children of Parents With Depression

Helping children understand a parent's mood disorder through open, honest communication fosters resiliency in those who might otherwise succumb to mental illness, according to Dr. Beardslee.

For children living in homes with depressed parents, promoting resilience through communication is the central component of a family-based intervention developed by Dr. Beardslee and his colleagues at the Judge Baker Children's Center in Boston.

Based on studies they conducted in the 1980s, Dr. Beardslee has identified core characteristics of resilient youth: a desire to accomplish developmental tasks outside the home, such as doing well in school or in sports; a commitment to relationships with friends, siblings, and parents; and an understanding that they are not to blame for a parent's illness.

Giving depressed parents the tools to build resilience in their children is central to the Prevention Intervention Project. The manualized, stepwise therapeutic strategy teaches parents to encourage children to pursue interests, relationships, and activities outside the home and to talk about the illness in a productive way.

The intervention is designed for use by physicians, school counselors, nurses, and mental health professionals.

Two models—one lecture based, the other clinician led—have been tested with promising results. In the lecture-based model, parents attend two group meetings without their children. In the clinician-led version, parents and children attend a series of 6-11 meetings facilitated by a clinician, as well as a family meeting led by the parents during which the illness is discussed.

Participants in both interventions receive information about mood disorders, risk, and resilience, and both interventions focus on removing misunderstanding, guilt, and blame.

In the clinician-led intervention, cognitive information is linked specifically to the individual's life and family experiences, while the lecture intervention presents that information in a group format with opportunity for discussion. Unlike in the clinician model, children of families receiving the lecture intervention are not seen directly; parents are encouraged to talk with their children.

In an examination of the efficacy of the programs at 1 year and 2 ½ years post intervention among 100 families randomly assigned to one of the two intervention models, parents in both conditions reported significant change in child-related behaviors and attitudes, and the amount of change increased over time. Children in both conditions reported increased understanding of parental illness, and internalizing scores for all of the children decreased (Pediatrics 2003;112:e119-31).

Although more change was seen in the clinician-led group, the long-standing positive effects of both interventions suggest that interventions built around family involvement, even if brief, “translate into significant mental health gains for children and families,” Dr. Beardslee said.

Perspective

By CARL C. BELL, M.D., president and CEO of Community Mental Health Council Inc. Chicago, and director of public and community psychiatry, University of Illinois at Chicago.

We live in a society that believes in “better living through chemistry.” Fortunately, there are those who rail against the trend of taking a pill for everything that ails us. But in the treatment of mental illness, hard work is critical to helping patients achieve health and well-being.

In my research, I have uncovered several key principles necessary to cultivate resilience and resistance in individuals so they won't need pills to manage clinical illness. We need to:

▸ Create a social fabric around individuals.

▸ Establish systems that promote interpersonal connectedness as a way to facilitate health behavior change.

▸ Develop infrastructures that promote social skills, personal value, and empowerment.

▸ Provide children with an adult protective shield to increase protective factors and decrease risk factors.

▸ Strive to minimize the experience and impact of trauma.

▸ Support quality psychosocial research at the level we have been supporting biomedical research.

Validated programs that incorporate these principles, such as the Preventive Intervention Project, need to be aggressively marketed. For example, people are more hyped about preventing maternal transmission of HIV than preventing parental transmission of depression because of the availability of clear-cut, proven, hard biologic interventions for HIV. To encourage a paradigm shift in mental illness, science needs to show equally strong evidence for psychosocial interventions, along with a strong advocacy campaign to convince people that psychosocial interventions are as valuable as biological ones.

Another obstacle is our couch-potato society's shortsighted preoccupation with how long something takes.

Some would argue that 6-11 manualized, evidence-based sessions aimed at helping a child keep from getting depressed is a significant time commitment, but consider the possible depression-related outcomes without such efforts: school failure, substance abuse, hopelessness, and suicide attempts. How can an individual or a society not make such a time investment?

It boils down to paying now or paying much, much more later, akin to the old Chinese proverb: “You are a fool if you wait until you are thirsty before you start digging your well.

BOSTON — Daily ingestion of fish oil tablets can decrease blood lipid levels in HIV-infected patients with hypertriglyceridemia associated with antiretroviral drug therapy, according to the results of a French study.

The prospective investigation included 122 HIV-infected patients taking antiretroviral therapy (ART); 58 were randomized to receive two 1-g capsules of a fish oil supplement t.i.d. This group experienced a median 26% reduction in triglyceride levels from baseline. In contrast, the median triglyceride levels of patients given a placebo increased 1%, Pierre de Truchis, M.D., reported at a conference on retroviruses and opportunistic infections.

“Triglyceride levels normalized in 22% of the [fish oil] recipients, but in only 7% of the placebo group,” said Dr. de Truchis of Hôpital Raymond Poincaré, Garches, France. Neither total nor HDL cholesterol levels changed over the course of the study in either group.

During a subsequent 8-week open-label phase of the study, patients in the original fish oil group maintained their triglyceride reductions while continuing fish oil supplementation, and patients originally given placebo experienced a median 21% decrease with the switch to fish oil tablets, he said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

At baseline, all of the patients in the study had triglyceride levels greater than 2 g/L with a mean triglyceride level of 4.5 g/L after 4 weeks of following an appropriate diet. Patients with baseline levels greater than 10 g/L were not randomized in the initial trial, but 10 such patients were included in the open-label phase. After 8 weeks of supplementation, this group experienced a 44% reduction in triglycerides, said Dr. de Truchis, suggesting that there was a benefit in patients with severe blood lipid elevation.

The fish oil supplements were well tolerated, and there were no significant differences in adverse events between groups, Dr. de Truchis said. Because of their efficacy and tolerability and the absence of drug interactions, fish oil supplements represent a potential first-line therapy for ART-associated hypertriglyceridemia. “Reducing blood lipid increases may lower the increased risk of cardiovascular disease associated with HIV infection and with antiretroviral therapy,” he said.

The fish oil supplementation in this study included a total of about 1 g/day each of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid—the equivalent of two meals containing oily fish per day. This formulation has been shown to reduce LDL cholesterol and triglyceride levels in adults without infection, according to Dr. De Truchis.

BOSTON — Daily ingestion of fish oil tablets can decrease blood lipid levels in HIV-infected patients with hypertriglyceridemia associated with antiretroviral drug therapy, according to the results of a French study.

The prospective investigation included 122 HIV-infected patients taking antiretroviral therapy (ART); 58 were randomized to receive two 1-g capsules of a fish oil supplement t.i.d. This group experienced a median 26% reduction in triglyceride levels from baseline. In contrast, the median triglyceride levels of patients given a placebo increased 1%, Pierre de Truchis, M.D., reported at a conference on retroviruses and opportunistic infections.

“Triglyceride levels normalized in 22% of the [fish oil] recipients, but in only 7% of the placebo group,” said Dr. de Truchis of Hôpital Raymond Poincaré, Garches, France. Neither total nor HDL cholesterol levels changed over the course of the study in either group.

During a subsequent 8-week open-label phase of the study, patients in the original fish oil group maintained their triglyceride reductions while continuing fish oil supplementation, and patients originally given placebo experienced a median 21% decrease with the switch to fish oil tablets, he said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

At baseline, all of the patients in the study had triglyceride levels greater than 2 g/L with a mean triglyceride level of 4.5 g/L after 4 weeks of following an appropriate diet. Patients with baseline levels greater than 10 g/L were not randomized in the initial trial, but 10 such patients were included in the open-label phase. After 8 weeks of supplementation, this group experienced a 44% reduction in triglycerides, said Dr. de Truchis, suggesting that there was a benefit in patients with severe blood lipid elevation.

The fish oil supplements were well tolerated, and there were no significant differences in adverse events between groups, Dr. de Truchis said. Because of their efficacy and tolerability and the absence of drug interactions, fish oil supplements represent a potential first-line therapy for ART-associated hypertriglyceridemia. “Reducing blood lipid increases may lower the increased risk of cardiovascular disease associated with HIV infection and with antiretroviral therapy,” he said.

The fish oil supplementation in this study included a total of about 1 g/day each of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid—the equivalent of two meals containing oily fish per day. This formulation has been shown to reduce LDL cholesterol and triglyceride levels in adults without infection, according to Dr. De Truchis.

BOSTON — Daily ingestion of fish oil tablets can decrease blood lipid levels in HIV-infected patients with hypertriglyceridemia associated with antiretroviral drug therapy, according to the results of a French study.

The prospective investigation included 122 HIV-infected patients taking antiretroviral therapy (ART); 58 were randomized to receive two 1-g capsules of a fish oil supplement t.i.d. This group experienced a median 26% reduction in triglyceride levels from baseline. In contrast, the median triglyceride levels of patients given a placebo increased 1%, Pierre de Truchis, M.D., reported at a conference on retroviruses and opportunistic infections.

“Triglyceride levels normalized in 22% of the [fish oil] recipients, but in only 7% of the placebo group,” said Dr. de Truchis of Hôpital Raymond Poincaré, Garches, France. Neither total nor HDL cholesterol levels changed over the course of the study in either group.

During a subsequent 8-week open-label phase of the study, patients in the original fish oil group maintained their triglyceride reductions while continuing fish oil supplementation, and patients originally given placebo experienced a median 21% decrease with the switch to fish oil tablets, he said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

At baseline, all of the patients in the study had triglyceride levels greater than 2 g/L with a mean triglyceride level of 4.5 g/L after 4 weeks of following an appropriate diet. Patients with baseline levels greater than 10 g/L were not randomized in the initial trial, but 10 such patients were included in the open-label phase. After 8 weeks of supplementation, this group experienced a 44% reduction in triglycerides, said Dr. de Truchis, suggesting that there was a benefit in patients with severe blood lipid elevation.

The fish oil supplements were well tolerated, and there were no significant differences in adverse events between groups, Dr. de Truchis said. Because of their efficacy and tolerability and the absence of drug interactions, fish oil supplements represent a potential first-line therapy for ART-associated hypertriglyceridemia. “Reducing blood lipid increases may lower the increased risk of cardiovascular disease associated with HIV infection and with antiretroviral therapy,” he said.

The fish oil supplementation in this study included a total of about 1 g/day each of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid—the equivalent of two meals containing oily fish per day. This formulation has been shown to reduce LDL cholesterol and triglyceride levels in adults without infection, according to Dr. De Truchis.

BOSTON — Patients receiving combination antiretroviral therapy to suppress HIV are at significantly increased risk for myocardial infarction, and the longer they take the drugs, the higher the risk, according to recent findings from an ongoing multicenter study.

Because the benefits of the so-called AIDS cocktails still far outweigh the associated cardiovascular risks, focus on convincing at-risk patients to modify lifestyle-related risk factors, rather than discontinuing the potent medications, Jens Lundgren, M.D., said during a symposium on the cardiovascular effects of antiretroviral therapy (ART) at a conference on retroviruses and opportunistic infections.

“In 1994, before we had combination antiretroviral therapy, the 1-year mortality of HIV-infected patients was 23%. Today, the mortality rate is about 1.5%-2%,” said Dr. Lundgren of the University of Copenhagen. “Clearly, the drugs are working, and patients are living longer. Now we're starting to see some of the longer-term events that we wouldn't be seeing if the drugs were not effective.”

Among 23,441 HIV-infected patients (median age 39 years) being treated with conventional or highly active ART (HAART) in the University of Copenhagen Data Collection on Adverse Events of Anti-HIV Drugs (DAD) trial, 277 myocardial infarctions were reported—approximately twice the number seen in the untreated HIV-infected population.

“Those are relatively small numbers, but this is a young population,” Dr. Lundgren said. “You wouldn't expect that many myocardial infarcts in that young a population. Still, the overall risk of having a heart attack remains low.”

And even though there's no question that treatment with antiretroviral drugs is an independent risk factor for MI, he said, “we do not have enough events to look at the contribution of HIV drug classes.”

In a separate analysis of the DAD data collected between 1999 and February 2004, Wafaa El-Sadr, M.D., of Columbia University, New York, and colleagues determined that patients' risk of MI rose 17% with each additional year of treatment after adjustment for other potential risk factors, and the increase was independent of both gender and age.

The risk increase was maintained when the investigators included repeat MIs in the analysis, and when they considered only patients who were treatment-naive when the study started. The risk increase was also stable when they included only those participants with definite MIs.

Not surprisingly, Dr. El-Sadr said, the odds of having a heart attack were independently increased by male gender, family history, previous cardiovascular disease, smoking, and every 5-year increment in age.

HIV patients' risk of heart disease should be evaluated prior to initiating drug therapy by conducting thorough medical histories and checking cholesterol levels and blood pressure, Dr. Lundgren advised. At-risk patients should be advised to modify some of the conventional risk factors, such as diet, exercise, and smoking, in an effort to compensate for some of the effects of the HIV drugs.

For example, the increased MI risk seen with ART is comparable to that associated with smoking, “and a lot of HIV patients, particularly in Europe, are smokers,” Dr. Lundgren said at the conference, sponsored by the Foundation for Retrovirology and Human Health. “Quit smoking, and your heart forgives you.”

There may also be a role for lipid-lowering therapy. According to a multifactor analysis of the DAD findings, changes in total cholesterol, triglycerides, and high-density lipoproteins were linked to increases in MI risk. The correlation between some antiretroviral drugs—particularly protease inhibitors—and increased lipids might partly explain the relationship between increased MI risk and duration of therapy, “but it cannot explain the whole increase,” Dr. El-Sadr said.

In the absence of definitive data on cause and effect, “it seems reasonable to evaluate lipid disorders in HIV-infected patients according to the same criteria used in the general population,” added symposium participant Esteban Martinez, M.D., of the University Hospital Clinic in Barcelona, Spain. “The impact of individual antiretroviral drugs on lipid parameters should be included among the factors to be considered when prescribing combination antiretroviral therapy,” he said.

Protease inhibitors in particular have been linked to increased lipid levels. Therefore, for treatment-naive patients with cardiovascular risk factors, Dr. Martinez advised avoiding drug regimens that include these agents and prescribing lipid-lowering therapy if necessary.

For at-risk patients already on HAART, lipid-lowering therapy should be tried first, followed by a change in the drug regimen if the desired effect is not achieved.

For example, at-risk patients on a regimen that includes protease inhibitors should be switched to nonnucleoside reverse transcriptase inhibitors or to an ART agent that has been shown to have lesser effects on lipids, such as atazanavir (Reyataz), Dr. Martinez recommended. Patients who take stavudine (Zerit) should switch to tenofovir (Viread), he advised.

BOSTON — Patients receiving combination antiretroviral therapy to suppress HIV are at significantly increased risk for myocardial infarction, and the longer they take the drugs, the higher the risk, according to recent findings from an ongoing multicenter study.

Because the benefits of the so-called AIDS cocktails still far outweigh the associated cardiovascular risks, focus on convincing at-risk patients to modify lifestyle-related risk factors, rather than discontinuing the potent medications, Jens Lundgren, M.D., said during a symposium on the cardiovascular effects of antiretroviral therapy (ART) at a conference on retroviruses and opportunistic infections.

“In 1994, before we had combination antiretroviral therapy, the 1-year mortality of HIV-infected patients was 23%. Today, the mortality rate is about 1.5%-2%,” said Dr. Lundgren of the University of Copenhagen. “Clearly, the drugs are working, and patients are living longer. Now we're starting to see some of the longer-term events that we wouldn't be seeing if the drugs were not effective.”

Among 23,441 HIV-infected patients (median age 39 years) being treated with conventional or highly active ART (HAART) in the University of Copenhagen Data Collection on Adverse Events of Anti-HIV Drugs (DAD) trial, 277 myocardial infarctions were reported—approximately twice the number seen in the untreated HIV-infected population.

“Those are relatively small numbers, but this is a young population,” Dr. Lundgren said. “You wouldn't expect that many myocardial infarcts in that young a population. Still, the overall risk of having a heart attack remains low.”

And even though there's no question that treatment with antiretroviral drugs is an independent risk factor for MI, he said, “we do not have enough events to look at the contribution of HIV drug classes.”

In a separate analysis of the DAD data collected between 1999 and February 2004, Wafaa El-Sadr, M.D., of Columbia University, New York, and colleagues determined that patients' risk of MI rose 17% with each additional year of treatment after adjustment for other potential risk factors, and the increase was independent of both gender and age.

The risk increase was maintained when the investigators included repeat MIs in the analysis, and when they considered only patients who were treatment-naive when the study started. The risk increase was also stable when they included only those participants with definite MIs.

Not surprisingly, Dr. El-Sadr said, the odds of having a heart attack were independently increased by male gender, family history, previous cardiovascular disease, smoking, and every 5-year increment in age.

HIV patients' risk of heart disease should be evaluated prior to initiating drug therapy by conducting thorough medical histories and checking cholesterol levels and blood pressure, Dr. Lundgren advised. At-risk patients should be advised to modify some of the conventional risk factors, such as diet, exercise, and smoking, in an effort to compensate for some of the effects of the HIV drugs.

For example, the increased MI risk seen with ART is comparable to that associated with smoking, “and a lot of HIV patients, particularly in Europe, are smokers,” Dr. Lundgren said at the conference, sponsored by the Foundation for Retrovirology and Human Health. “Quit smoking, and your heart forgives you.”

There may also be a role for lipid-lowering therapy. According to a multifactor analysis of the DAD findings, changes in total cholesterol, triglycerides, and high-density lipoproteins were linked to increases in MI risk. The correlation between some antiretroviral drugs—particularly protease inhibitors—and increased lipids might partly explain the relationship between increased MI risk and duration of therapy, “but it cannot explain the whole increase,” Dr. El-Sadr said.

In the absence of definitive data on cause and effect, “it seems reasonable to evaluate lipid disorders in HIV-infected patients according to the same criteria used in the general population,” added symposium participant Esteban Martinez, M.D., of the University Hospital Clinic in Barcelona, Spain. “The impact of individual antiretroviral drugs on lipid parameters should be included among the factors to be considered when prescribing combination antiretroviral therapy,” he said.

Protease inhibitors in particular have been linked to increased lipid levels. Therefore, for treatment-naive patients with cardiovascular risk factors, Dr. Martinez advised avoiding drug regimens that include these agents and prescribing lipid-lowering therapy if necessary.

For at-risk patients already on HAART, lipid-lowering therapy should be tried first, followed by a change in the drug regimen if the desired effect is not achieved.

For example, at-risk patients on a regimen that includes protease inhibitors should be switched to nonnucleoside reverse transcriptase inhibitors or to an ART agent that has been shown to have lesser effects on lipids, such as atazanavir (Reyataz), Dr. Martinez recommended. Patients who take stavudine (Zerit) should switch to tenofovir (Viread), he advised.

BOSTON — Patients receiving combination antiretroviral therapy to suppress HIV are at significantly increased risk for myocardial infarction, and the longer they take the drugs, the higher the risk, according to recent findings from an ongoing multicenter study.

Because the benefits of the so-called AIDS cocktails still far outweigh the associated cardiovascular risks, focus on convincing at-risk patients to modify lifestyle-related risk factors, rather than discontinuing the potent medications, Jens Lundgren, M.D., said during a symposium on the cardiovascular effects of antiretroviral therapy (ART) at a conference on retroviruses and opportunistic infections.

“In 1994, before we had combination antiretroviral therapy, the 1-year mortality of HIV-infected patients was 23%. Today, the mortality rate is about 1.5%-2%,” said Dr. Lundgren of the University of Copenhagen. “Clearly, the drugs are working, and patients are living longer. Now we're starting to see some of the longer-term events that we wouldn't be seeing if the drugs were not effective.”

Among 23,441 HIV-infected patients (median age 39 years) being treated with conventional or highly active ART (HAART) in the University of Copenhagen Data Collection on Adverse Events of Anti-HIV Drugs (DAD) trial, 277 myocardial infarctions were reported—approximately twice the number seen in the untreated HIV-infected population.

“Those are relatively small numbers, but this is a young population,” Dr. Lundgren said. “You wouldn't expect that many myocardial infarcts in that young a population. Still, the overall risk of having a heart attack remains low.”

And even though there's no question that treatment with antiretroviral drugs is an independent risk factor for MI, he said, “we do not have enough events to look at the contribution of HIV drug classes.”

In a separate analysis of the DAD data collected between 1999 and February 2004, Wafaa El-Sadr, M.D., of Columbia University, New York, and colleagues determined that patients' risk of MI rose 17% with each additional year of treatment after adjustment for other potential risk factors, and the increase was independent of both gender and age.

The risk increase was maintained when the investigators included repeat MIs in the analysis, and when they considered only patients who were treatment-naive when the study started. The risk increase was also stable when they included only those participants with definite MIs.

Not surprisingly, Dr. El-Sadr said, the odds of having a heart attack were independently increased by male gender, family history, previous cardiovascular disease, smoking, and every 5-year increment in age.

HIV patients' risk of heart disease should be evaluated prior to initiating drug therapy by conducting thorough medical histories and checking cholesterol levels and blood pressure, Dr. Lundgren advised. At-risk patients should be advised to modify some of the conventional risk factors, such as diet, exercise, and smoking, in an effort to compensate for some of the effects of the HIV drugs.

For example, the increased MI risk seen with ART is comparable to that associated with smoking, “and a lot of HIV patients, particularly in Europe, are smokers,” Dr. Lundgren said at the conference, sponsored by the Foundation for Retrovirology and Human Health. “Quit smoking, and your heart forgives you.”

There may also be a role for lipid-lowering therapy. According to a multifactor analysis of the DAD findings, changes in total cholesterol, triglycerides, and high-density lipoproteins were linked to increases in MI risk. The correlation between some antiretroviral drugs—particularly protease inhibitors—and increased lipids might partly explain the relationship between increased MI risk and duration of therapy, “but it cannot explain the whole increase,” Dr. El-Sadr said.

In the absence of definitive data on cause and effect, “it seems reasonable to evaluate lipid disorders in HIV-infected patients according to the same criteria used in the general population,” added symposium participant Esteban Martinez, M.D., of the University Hospital Clinic in Barcelona, Spain. “The impact of individual antiretroviral drugs on lipid parameters should be included among the factors to be considered when prescribing combination antiretroviral therapy,” he said.

Protease inhibitors in particular have been linked to increased lipid levels. Therefore, for treatment-naive patients with cardiovascular risk factors, Dr. Martinez advised avoiding drug regimens that include these agents and prescribing lipid-lowering therapy if necessary.

For at-risk patients already on HAART, lipid-lowering therapy should be tried first, followed by a change in the drug regimen if the desired effect is not achieved.

For example, at-risk patients on a regimen that includes protease inhibitors should be switched to nonnucleoside reverse transcriptase inhibitors or to an ART agent that has been shown to have lesser effects on lipids, such as atazanavir (Reyataz), Dr. Martinez recommended. Patients who take stavudine (Zerit) should switch to tenofovir (Viread), he advised.

Since October 2002, physicians have been allowed to apply for waivers of the special registration requirements defined in the Controlled Substances Act to prescribe buprenorphine in treatment settings other than a traditional opioid treatment program.

“However, physicians have been reluctant to embrace this treatment option, possibly due to concerns regarding use of other illicit substances among patients who abuse pain relievers,” said Dr. Woodard of Baylor College of Medicine, Houston.

To estimate the prevalence of substance co-use among abusers of prescription analgesics, Dr. Woodard and her colleagues reviewed data from the 2000 National Household Survey on Drug Abuse, which showed that about 2.9% of Americans reported nonmedical use of pain relievers during the prior year, and 93% of those pain relievers were opioid analgesics.

Among users of prescription pain relievers, 23% reported heavy alcohol use, 46% reported using marijuana, and 46% reported co-using other illicit substances, Dr. Woodard reported at the annual meeting of the Society of General Internal Medicine.

Heavy use of alcohol was defined as having five or more drinks five times within the month prior to the survey. Rates for use of marijuana and other illicit substances were based on use during the year prior to the survey.

The investigators used logistic regression analysis to identify demographic factors associated with substance co-use in this population. The predictors considered were age, sex, race, education, employment, household income, veteran status, and metropolitan statistical area. “Controlling for other predictors in the model, age, race, and marital status were all broadly associated with heavy alcohol, marijuana, or other illicit substance co-use,” Dr. Woodard said.

People aged younger than 50 years were significantly more likely to be co-users of all three types of substances than were those older than 50; white individuals were significantly more likely to co-use all three types compared with individuals of other races/ethnicities; and single people were significantly more likely than were those who were married to co-use all three types.

Men were significantly more likely than were women to co-use heavy alcohol and marijuana, and college-educated individuals were significantly more likely than were their less-educated counterparts to co-use the other illicit substances.

Since October 2002, physicians have been allowed to apply for waivers of the special registration requirements defined in the Controlled Substances Act to prescribe buprenorphine in treatment settings other than a traditional opioid treatment program.

“However, physicians have been reluctant to embrace this treatment option, possibly due to concerns regarding use of other illicit substances among patients who abuse pain relievers,” said Dr. Woodard of Baylor College of Medicine, Houston.

To estimate the prevalence of substance co-use among abusers of prescription analgesics, Dr. Woodard and her colleagues reviewed data from the 2000 National Household Survey on Drug Abuse, which showed that about 2.9% of Americans reported nonmedical use of pain relievers during the prior year, and 93% of those pain relievers were opioid analgesics.

Among users of prescription pain relievers, 23% reported heavy alcohol use, 46% reported using marijuana, and 46% reported co-using other illicit substances, Dr. Woodard reported at the annual meeting of the Society of General Internal Medicine.

Heavy use of alcohol was defined as having five or more drinks five times within the month prior to the survey. Rates for use of marijuana and other illicit substances were based on use during the year prior to the survey.

The investigators used logistic regression analysis to identify demographic factors associated with substance co-use in this population. The predictors considered were age, sex, race, education, employment, household income, veteran status, and metropolitan statistical area. “Controlling for other predictors in the model, age, race, and marital status were all broadly associated with heavy alcohol, marijuana, or other illicit substance co-use,” Dr. Woodard said.

People aged younger than 50 years were significantly more likely to be co-users of all three types of substances than were those older than 50; white individuals were significantly more likely to co-use all three types compared with individuals of other races/ethnicities; and single people were significantly more likely than were those who were married to co-use all three types.

Men were significantly more likely than were women to co-use heavy alcohol and marijuana, and college-educated individuals were significantly more likely than were their less-educated counterparts to co-use the other illicit substances.

Since October 2002, physicians have been allowed to apply for waivers of the special registration requirements defined in the Controlled Substances Act to prescribe buprenorphine in treatment settings other than a traditional opioid treatment program.

“However, physicians have been reluctant to embrace this treatment option, possibly due to concerns regarding use of other illicit substances among patients who abuse pain relievers,” said Dr. Woodard of Baylor College of Medicine, Houston.

To estimate the prevalence of substance co-use among abusers of prescription analgesics, Dr. Woodard and her colleagues reviewed data from the 2000 National Household Survey on Drug Abuse, which showed that about 2.9% of Americans reported nonmedical use of pain relievers during the prior year, and 93% of those pain relievers were opioid analgesics.

Among users of prescription pain relievers, 23% reported heavy alcohol use, 46% reported using marijuana, and 46% reported co-using other illicit substances, Dr. Woodard reported at the annual meeting of the Society of General Internal Medicine.

Heavy use of alcohol was defined as having five or more drinks five times within the month prior to the survey. Rates for use of marijuana and other illicit substances were based on use during the year prior to the survey.

The investigators used logistic regression analysis to identify demographic factors associated with substance co-use in this population. The predictors considered were age, sex, race, education, employment, household income, veteran status, and metropolitan statistical area. “Controlling for other predictors in the model, age, race, and marital status were all broadly associated with heavy alcohol, marijuana, or other illicit substance co-use,” Dr. Woodard said.

People aged younger than 50 years were significantly more likely to be co-users of all three types of substances than were those older than 50; white individuals were significantly more likely to co-use all three types compared with individuals of other races/ethnicities; and single people were significantly more likely than were those who were married to co-use all three types.

Men were significantly more likely than were women to co-use heavy alcohol and marijuana, and college-educated individuals were significantly more likely than were their less-educated counterparts to co-use the other illicit substances.

BERLIN – The most common second-generation antipsychotics prescribed to young people with various psychotic, mood, and behavioral disorders adversely affect all components of body composition and lead to dyslipidemia in this patient population, a study has shown.

Youths who have never taken antipsychotics and those cotreated with olanzapine (Zyprexa) and divalproex (Depakote) who experience significant early weight gain are at highest risk for the metabolic changes, Christoph U. Correll, M.D., said in a presentation at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

“Second-generation antipsychotics are widely used in young patients, but limited comparative data exist on their effects on body composition and lipid metabolism,” said Dr. Correll of Zucker Hillside Hospital in Glen Oaks, N.Y. He, along with his colleagues, prospectively evaluated the relative effects on these factors of olanzapine (Zyprexa), risperidone (Risperdal), or quetiapine (Seroquel)–the three most widely prescribed drugs in this particular class.

The open-label study included youth between the ages of 5 and 18 years with a DSM-IV diagnosis of psychotic, mood, and/or disruptive behavior disorders who had begun or switched to treatment with one of the three medications within 7 days of the start of the investigation. Exclusion criteria included a history of any eating disorder, active thyroid or severe medical disorder, and pregnancy. All subjects were assessed at baseline and monthly for height, weight, body mass index, total fat mass and percentage fat (via bioimpedance measurement), and waist circumference. In addition, fasting blood leptin, prolactin, and antipsychotic serum levels were measured at baseline, week 4, and week 12.

After 12 weeks of treatment, the weight, body mass index (BMI), fat mass and percentage fat, and waist circumference of all of the 174 youth in the study–including 57 on olanzapine, 70 on risperidone, and 47 on quetiapine–increased significantly, Dr. Correll said. The greatest increase in all measures was seen in those youths taking olanzapine, followed by risperidone, then quetiapine, he said. Additionally, nearly 81% of the subjects taking olanzapine experienced extreme weight gain–described as an increase in weight from baseline of 7% or more–compared with 57% and 43% of risperidone and quetiapine subjects, respectively.

All of the study participants experienced significant increases in total cholesterol, LDL cholesterol, and triglycerides. A separate analysis comparing pretreated and antipsychotic-naive patients showed that only the olanzapine-induced cholesterol and triglyceride increases remained significant. “Nevertheless, 19.9% of the youths experienced new-onset dyslipidemia, with similar rates for all three drugs,” Dr. Correll reported.

Multiple regression analysis identified the following correlates of weight gain: weight increase at 4 weeks, baseline-to-end increases in leptin, antipsychotic naive status, olanzapine treatment, and divalproex cotreatment.

With respect to lipids, predictors for both cholesterol increase and for triglyceride increase were low baseline cholesterol level, antidepressant cotreatment, and 12-week BMI change. Male gender was a predictor for cholesterol increase only.

“What we're seeing is that these drugs have an impact on all aspects of body composition, and they lead to dyslipidemia, which further increases the cardiovascular risk profile. We're not suggesting they shouldn't be used because obviously these drugs have an important role, but they should be used carefully, and these side effects should be monitored regularly.

“Pretreatment dietary and lifestyle counseling, particularly among those at highest risk, cannot be overlooked,” Dr. Correll concluded.

BERLIN – The most common second-generation antipsychotics prescribed to young people with various psychotic, mood, and behavioral disorders adversely affect all components of body composition and lead to dyslipidemia in this patient population, a study has shown.

Youths who have never taken antipsychotics and those cotreated with olanzapine (Zyprexa) and divalproex (Depakote) who experience significant early weight gain are at highest risk for the metabolic changes, Christoph U. Correll, M.D., said in a presentation at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

“Second-generation antipsychotics are widely used in young patients, but limited comparative data exist on their effects on body composition and lipid metabolism,” said Dr. Correll of Zucker Hillside Hospital in Glen Oaks, N.Y. He, along with his colleagues, prospectively evaluated the relative effects on these factors of olanzapine (Zyprexa), risperidone (Risperdal), or quetiapine (Seroquel)–the three most widely prescribed drugs in this particular class.

The open-label study included youth between the ages of 5 and 18 years with a DSM-IV diagnosis of psychotic, mood, and/or disruptive behavior disorders who had begun or switched to treatment with one of the three medications within 7 days of the start of the investigation. Exclusion criteria included a history of any eating disorder, active thyroid or severe medical disorder, and pregnancy. All subjects were assessed at baseline and monthly for height, weight, body mass index, total fat mass and percentage fat (via bioimpedance measurement), and waist circumference. In addition, fasting blood leptin, prolactin, and antipsychotic serum levels were measured at baseline, week 4, and week 12.

After 12 weeks of treatment, the weight, body mass index (BMI), fat mass and percentage fat, and waist circumference of all of the 174 youth in the study–including 57 on olanzapine, 70 on risperidone, and 47 on quetiapine–increased significantly, Dr. Correll said. The greatest increase in all measures was seen in those youths taking olanzapine, followed by risperidone, then quetiapine, he said. Additionally, nearly 81% of the subjects taking olanzapine experienced extreme weight gain–described as an increase in weight from baseline of 7% or more–compared with 57% and 43% of risperidone and quetiapine subjects, respectively.

All of the study participants experienced significant increases in total cholesterol, LDL cholesterol, and triglycerides. A separate analysis comparing pretreated and antipsychotic-naive patients showed that only the olanzapine-induced cholesterol and triglyceride increases remained significant. “Nevertheless, 19.9% of the youths experienced new-onset dyslipidemia, with similar rates for all three drugs,” Dr. Correll reported.

Multiple regression analysis identified the following correlates of weight gain: weight increase at 4 weeks, baseline-to-end increases in leptin, antipsychotic naive status, olanzapine treatment, and divalproex cotreatment.

With respect to lipids, predictors for both cholesterol increase and for triglyceride increase were low baseline cholesterol level, antidepressant cotreatment, and 12-week BMI change. Male gender was a predictor for cholesterol increase only.

“What we're seeing is that these drugs have an impact on all aspects of body composition, and they lead to dyslipidemia, which further increases the cardiovascular risk profile. We're not suggesting they shouldn't be used because obviously these drugs have an important role, but they should be used carefully, and these side effects should be monitored regularly.

“Pretreatment dietary and lifestyle counseling, particularly among those at highest risk, cannot be overlooked,” Dr. Correll concluded.

BERLIN – The most common second-generation antipsychotics prescribed to young people with various psychotic, mood, and behavioral disorders adversely affect all components of body composition and lead to dyslipidemia in this patient population, a study has shown.

Youths who have never taken antipsychotics and those cotreated with olanzapine (Zyprexa) and divalproex (Depakote) who experience significant early weight gain are at highest risk for the metabolic changes, Christoph U. Correll, M.D., said in a presentation at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

“Second-generation antipsychotics are widely used in young patients, but limited comparative data exist on their effects on body composition and lipid metabolism,” said Dr. Correll of Zucker Hillside Hospital in Glen Oaks, N.Y. He, along with his colleagues, prospectively evaluated the relative effects on these factors of olanzapine (Zyprexa), risperidone (Risperdal), or quetiapine (Seroquel)–the three most widely prescribed drugs in this particular class.

The open-label study included youth between the ages of 5 and 18 years with a DSM-IV diagnosis of psychotic, mood, and/or disruptive behavior disorders who had begun or switched to treatment with one of the three medications within 7 days of the start of the investigation. Exclusion criteria included a history of any eating disorder, active thyroid or severe medical disorder, and pregnancy. All subjects were assessed at baseline and monthly for height, weight, body mass index, total fat mass and percentage fat (via bioimpedance measurement), and waist circumference. In addition, fasting blood leptin, prolactin, and antipsychotic serum levels were measured at baseline, week 4, and week 12.

After 12 weeks of treatment, the weight, body mass index (BMI), fat mass and percentage fat, and waist circumference of all of the 174 youth in the study–including 57 on olanzapine, 70 on risperidone, and 47 on quetiapine–increased significantly, Dr. Correll said. The greatest increase in all measures was seen in those youths taking olanzapine, followed by risperidone, then quetiapine, he said. Additionally, nearly 81% of the subjects taking olanzapine experienced extreme weight gain–described as an increase in weight from baseline of 7% or more–compared with 57% and 43% of risperidone and quetiapine subjects, respectively.

All of the study participants experienced significant increases in total cholesterol, LDL cholesterol, and triglycerides. A separate analysis comparing pretreated and antipsychotic-naive patients showed that only the olanzapine-induced cholesterol and triglyceride increases remained significant. “Nevertheless, 19.9% of the youths experienced new-onset dyslipidemia, with similar rates for all three drugs,” Dr. Correll reported.

Multiple regression analysis identified the following correlates of weight gain: weight increase at 4 weeks, baseline-to-end increases in leptin, antipsychotic naive status, olanzapine treatment, and divalproex cotreatment.

With respect to lipids, predictors for both cholesterol increase and for triglyceride increase were low baseline cholesterol level, antidepressant cotreatment, and 12-week BMI change. Male gender was a predictor for cholesterol increase only.

“What we're seeing is that these drugs have an impact on all aspects of body composition, and they lead to dyslipidemia, which further increases the cardiovascular risk profile. We're not suggesting they shouldn't be used because obviously these drugs have an important role, but they should be used carefully, and these side effects should be monitored regularly.

“Pretreatment dietary and lifestyle counseling, particularly among those at highest risk, cannot be overlooked,” Dr. Correll concluded.

BOSTON — Patients receiving combination antiretroviral therapy to suppress HIV are at significantly increased risk for myocardial infarction, and the longer they take the drugs, the higher the risk, according to recent findings from an ongoing multicenter study.

Because the benefits of the so-called AIDS cocktails still far outweigh the associated cardiovascular risks, physicians should focus on convincing at-risk patients to modify lifestyle-related risk factors, rather than discontinuing the potent medications, Jens Lundgren, M.D., said during a symposium on the cardiovascular effects of antiretroviral therapy (ART) at a conference on retroviruses and opportunistic infections.

“In 1994, before we had combination antiretroviral therapy, the 1-year mortality of HIV-infected patients was 23%. Today, the mortality rate is about 1.5%-2%,” said Dr. Lundgren of the University of Copenhagen. “Clearly, the drugs are working, and patients are living longer. Now we're starting to see some of the longer-term events that we wouldn't be seeing if the drugs were not effective.”

Among 23,441 HIV-infected patients (median age 39 years) being treated with conventional or highly active ART (HAART) in the University of Copenhagen Data Collection on Adverse Events of Anti-HIV Drugs (DAD) trial, 277 myocardial infarctions were reported—about twice the number seen in the untreated population.

“Those are relatively small numbers, but this is a young population,” Dr. Lundgren said. “You wouldn't expect that many myocardial infarcts in that young a population. Still, the overall risk of having a heart attack remains low.” And even though there's no question that treatment with antiretroviral drugs is an independent risk factor for MI, he said, “we do not have enough events to look at the contribution of HIV drug classes.”

In a separate analysis of the DAD data collected between 1999 and February 2004, Wafaa El-Sadr, M.D., of Columbia University, New York, and colleagues determined that patients' risk of MI rose 17% with each additional year of treatment after adjustment for other potential risk factors, and the increase was independent of both gender and age.

The risk increase was maintained when the investigators included repeat MIs in the analysis, and when they considered only patients who were treatment-naive when the study started. The risk increase was also stable when they included only those participants with definite MIs. Not surprisingly, Dr. El-Sadr said, the odds of having a heart attack were independently increased by male gender, family history, previous cardiovascular disease, smoking, and every 5-year increment in age.

Physicians should routinely evaluate HIV patients' risk of heart disease prior to initiating drug therapy by conducting thorough medical histories and checking cholesterol levels and blood pressure, Dr. Lundgren advised. At-risk patients should be advised to modify some of the conventional risk factors, such as diet, exercise, and smoking, in an effort to compensate for some of the effects of the HIV drugs.

For example, the increased MI risk seen with ART is comparable to that associated with smoking, “and a lot of HIV patients, particularly in Europe, are smokers,” Dr. Lundgren said at the conference, sponsored by the Foundation for Retrovirology and Human Health. “Quit smoking, and your heart forgives you.”

There may also be a role for lipid-lowering therapy. According to a multifactor analysis of the DAD findings, changes in total cholesterol, triglycerides, and high-density lipoproteins were linked to increases in MI risk. The correlation between some antiretroviral drugs—particularly protease inhibitors—and increased lipids might partly explain the relationship between increased MI risk and duration of therapy, “but it cannot explain the whole increase,” Dr. El-Sadr said.

In the absence of definitive data on cause and effect, “it seems reasonable to evaluate lipid disorders in HIV-infected patients according to the same criteria used in the general population,” added symposium participant Esteban Martinez, M.D., of the University Hospital Clinic in Barcelona, Spain. “The impact of individual antiretroviral drugs on lipid parameters should be included among the factors to be considered when prescribing combination antiretroviral therapy,” he said.

Protease inhibitors in particular have been linked to increased lipid levels. Therefore, for treatment-naive patients with cardiovascular risk factors, Dr. Martinez advised avoiding drug regimens that include these agents and prescribing lipid-lowering therapy if necessary.

For at-risk patients already on HAART, lipid-lowering therapy should be tried first, followed by a change in the drug regimen if the desired effect is not achieved. For example, at-risk patients on a regimen that includes protease inhibitors should be switched to nonnucleoside reverse transcriptase inhibitors or to an ART agent that has been shown to have lesser effects on lipids, such as atazanavir (Reyataz), Dr. Martinez recommended. Patients who take stavudine (Zerit) should switch to tenofovir (Viread), he advised.

BOSTON — Patients receiving combination antiretroviral therapy to suppress HIV are at significantly increased risk for myocardial infarction, and the longer they take the drugs, the higher the risk, according to recent findings from an ongoing multicenter study.

Because the benefits of the so-called AIDS cocktails still far outweigh the associated cardiovascular risks, physicians should focus on convincing at-risk patients to modify lifestyle-related risk factors, rather than discontinuing the potent medications, Jens Lundgren, M.D., said during a symposium on the cardiovascular effects of antiretroviral therapy (ART) at a conference on retroviruses and opportunistic infections.

“In 1994, before we had combination antiretroviral therapy, the 1-year mortality of HIV-infected patients was 23%. Today, the mortality rate is about 1.5%-2%,” said Dr. Lundgren of the University of Copenhagen. “Clearly, the drugs are working, and patients are living longer. Now we're starting to see some of the longer-term events that we wouldn't be seeing if the drugs were not effective.”

Among 23,441 HIV-infected patients (median age 39 years) being treated with conventional or highly active ART (HAART) in the University of Copenhagen Data Collection on Adverse Events of Anti-HIV Drugs (DAD) trial, 277 myocardial infarctions were reported—about twice the number seen in the untreated population.

“Those are relatively small numbers, but this is a young population,” Dr. Lundgren said. “You wouldn't expect that many myocardial infarcts in that young a population. Still, the overall risk of having a heart attack remains low.” And even though there's no question that treatment with antiretroviral drugs is an independent risk factor for MI, he said, “we do not have enough events to look at the contribution of HIV drug classes.”

In a separate analysis of the DAD data collected between 1999 and February 2004, Wafaa El-Sadr, M.D., of Columbia University, New York, and colleagues determined that patients' risk of MI rose 17% with each additional year of treatment after adjustment for other potential risk factors, and the increase was independent of both gender and age.

The risk increase was maintained when the investigators included repeat MIs in the analysis, and when they considered only patients who were treatment-naive when the study started. The risk increase was also stable when they included only those participants with definite MIs. Not surprisingly, Dr. El-Sadr said, the odds of having a heart attack were independently increased by male gender, family history, previous cardiovascular disease, smoking, and every 5-year increment in age.

Physicians should routinely evaluate HIV patients' risk of heart disease prior to initiating drug therapy by conducting thorough medical histories and checking cholesterol levels and blood pressure, Dr. Lundgren advised. At-risk patients should be advised to modify some of the conventional risk factors, such as diet, exercise, and smoking, in an effort to compensate for some of the effects of the HIV drugs.

For example, the increased MI risk seen with ART is comparable to that associated with smoking, “and a lot of HIV patients, particularly in Europe, are smokers,” Dr. Lundgren said at the conference, sponsored by the Foundation for Retrovirology and Human Health. “Quit smoking, and your heart forgives you.”

There may also be a role for lipid-lowering therapy. According to a multifactor analysis of the DAD findings, changes in total cholesterol, triglycerides, and high-density lipoproteins were linked to increases in MI risk. The correlation between some antiretroviral drugs—particularly protease inhibitors—and increased lipids might partly explain the relationship between increased MI risk and duration of therapy, “but it cannot explain the whole increase,” Dr. El-Sadr said.

In the absence of definitive data on cause and effect, “it seems reasonable to evaluate lipid disorders in HIV-infected patients according to the same criteria used in the general population,” added symposium participant Esteban Martinez, M.D., of the University Hospital Clinic in Barcelona, Spain. “The impact of individual antiretroviral drugs on lipid parameters should be included among the factors to be considered when prescribing combination antiretroviral therapy,” he said.

Protease inhibitors in particular have been linked to increased lipid levels. Therefore, for treatment-naive patients with cardiovascular risk factors, Dr. Martinez advised avoiding drug regimens that include these agents and prescribing lipid-lowering therapy if necessary.

For at-risk patients already on HAART, lipid-lowering therapy should be tried first, followed by a change in the drug regimen if the desired effect is not achieved. For example, at-risk patients on a regimen that includes protease inhibitors should be switched to nonnucleoside reverse transcriptase inhibitors or to an ART agent that has been shown to have lesser effects on lipids, such as atazanavir (Reyataz), Dr. Martinez recommended. Patients who take stavudine (Zerit) should switch to tenofovir (Viread), he advised.

BOSTON — Patients receiving combination antiretroviral therapy to suppress HIV are at significantly increased risk for myocardial infarction, and the longer they take the drugs, the higher the risk, according to recent findings from an ongoing multicenter study.

Because the benefits of the so-called AIDS cocktails still far outweigh the associated cardiovascular risks, physicians should focus on convincing at-risk patients to modify lifestyle-related risk factors, rather than discontinuing the potent medications, Jens Lundgren, M.D., said during a symposium on the cardiovascular effects of antiretroviral therapy (ART) at a conference on retroviruses and opportunistic infections.

“In 1994, before we had combination antiretroviral therapy, the 1-year mortality of HIV-infected patients was 23%. Today, the mortality rate is about 1.5%-2%,” said Dr. Lundgren of the University of Copenhagen. “Clearly, the drugs are working, and patients are living longer. Now we're starting to see some of the longer-term events that we wouldn't be seeing if the drugs were not effective.”

Among 23,441 HIV-infected patients (median age 39 years) being treated with conventional or highly active ART (HAART) in the University of Copenhagen Data Collection on Adverse Events of Anti-HIV Drugs (DAD) trial, 277 myocardial infarctions were reported—about twice the number seen in the untreated population.

“Those are relatively small numbers, but this is a young population,” Dr. Lundgren said. “You wouldn't expect that many myocardial infarcts in that young a population. Still, the overall risk of having a heart attack remains low.” And even though there's no question that treatment with antiretroviral drugs is an independent risk factor for MI, he said, “we do not have enough events to look at the contribution of HIV drug classes.”

In a separate analysis of the DAD data collected between 1999 and February 2004, Wafaa El-Sadr, M.D., of Columbia University, New York, and colleagues determined that patients' risk of MI rose 17% with each additional year of treatment after adjustment for other potential risk factors, and the increase was independent of both gender and age.

The risk increase was maintained when the investigators included repeat MIs in the analysis, and when they considered only patients who were treatment-naive when the study started. The risk increase was also stable when they included only those participants with definite MIs. Not surprisingly, Dr. El-Sadr said, the odds of having a heart attack were independently increased by male gender, family history, previous cardiovascular disease, smoking, and every 5-year increment in age.

Physicians should routinely evaluate HIV patients' risk of heart disease prior to initiating drug therapy by conducting thorough medical histories and checking cholesterol levels and blood pressure, Dr. Lundgren advised. At-risk patients should be advised to modify some of the conventional risk factors, such as diet, exercise, and smoking, in an effort to compensate for some of the effects of the HIV drugs.

For example, the increased MI risk seen with ART is comparable to that associated with smoking, “and a lot of HIV patients, particularly in Europe, are smokers,” Dr. Lundgren said at the conference, sponsored by the Foundation for Retrovirology and Human Health. “Quit smoking, and your heart forgives you.”

There may also be a role for lipid-lowering therapy. According to a multifactor analysis of the DAD findings, changes in total cholesterol, triglycerides, and high-density lipoproteins were linked to increases in MI risk. The correlation between some antiretroviral drugs—particularly protease inhibitors—and increased lipids might partly explain the relationship between increased MI risk and duration of therapy, “but it cannot explain the whole increase,” Dr. El-Sadr said.

In the absence of definitive data on cause and effect, “it seems reasonable to evaluate lipid disorders in HIV-infected patients according to the same criteria used in the general population,” added symposium participant Esteban Martinez, M.D., of the University Hospital Clinic in Barcelona, Spain. “The impact of individual antiretroviral drugs on lipid parameters should be included among the factors to be considered when prescribing combination antiretroviral therapy,” he said.

Protease inhibitors in particular have been linked to increased lipid levels. Therefore, for treatment-naive patients with cardiovascular risk factors, Dr. Martinez advised avoiding drug regimens that include these agents and prescribing lipid-lowering therapy if necessary.

For at-risk patients already on HAART, lipid-lowering therapy should be tried first, followed by a change in the drug regimen if the desired effect is not achieved. For example, at-risk patients on a regimen that includes protease inhibitors should be switched to nonnucleoside reverse transcriptase inhibitors or to an ART agent that has been shown to have lesser effects on lipids, such as atazanavir (Reyataz), Dr. Martinez recommended. Patients who take stavudine (Zerit) should switch to tenofovir (Viread), he advised.

ORLANDO, FLA. — Consistent, moderate exercise can significantly improve the severity of restless legs syndrome symptoms without medication, a study has shown.

Despite evidence that lifestyle factors play an important role in RLS, “virtually all research studies have focused on pharmacologic therapies,” Fred Tudiver, M.D., said at the annual meeting of the North American Primary Care Research Group.

Dr. Tudiver and colleagues at East Tennessee State University in Johnson City randomized 11 of 28 patients to a reconditioning exercise program; the remaining 17 received no intervention. The intervention included 12 weeks of light- to moderate-intensity aerobic and muscular strength training three times per week.

Patients in the study—all of whom were at least 18 years old (average age 53) and had a diagnosis of RLS—were recruited from a community-based family medicine teaching center and a hospital-based wellness center. Exclusion criteria were anemia, any orthopedic condition that limited ambulation, any coronary event in the previous 6 months, uncontrolled hypertension, and current use of medication for RLS.

Before and after the intervention, patients completed the International Restless Legs Syndrome Study Group Rating Scale, a questionnaire that assessed symptom frequency and severity on a scale of 0–40.

At baseline, patients in both groups did not differ significantly in their RLS severity scores. After the 12-week intervention, however, median scores for patients in the exercise group had improved from 20.6 to 13.1, while median scores for patients in the control group went from 22.5 to 21.5.

“The results suggest a promising, simple, community-based intervention that can be prescribed to patients in family practice settings,” Dr. Tudiver said.

ORLANDO, FLA. — Consistent, moderate exercise can significantly improve the severity of restless legs syndrome symptoms without medication, a study has shown.

Despite evidence that lifestyle factors play an important role in RLS, “virtually all research studies have focused on pharmacologic therapies,” Fred Tudiver, M.D., said at the annual meeting of the North American Primary Care Research Group.

Dr. Tudiver and colleagues at East Tennessee State University in Johnson City randomized 11 of 28 patients to a reconditioning exercise program; the remaining 17 received no intervention. The intervention included 12 weeks of light- to moderate-intensity aerobic and muscular strength training three times per week.

Patients in the study—all of whom were at least 18 years old (average age 53) and had a diagnosis of RLS—were recruited from a community-based family medicine teaching center and a hospital-based wellness center. Exclusion criteria were anemia, any orthopedic condition that limited ambulation, any coronary event in the previous 6 months, uncontrolled hypertension, and current use of medication for RLS.

Before and after the intervention, patients completed the International Restless Legs Syndrome Study Group Rating Scale, a questionnaire that assessed symptom frequency and severity on a scale of 0–40.

At baseline, patients in both groups did not differ significantly in their RLS severity scores. After the 12-week intervention, however, median scores for patients in the exercise group had improved from 20.6 to 13.1, while median scores for patients in the control group went from 22.5 to 21.5.

“The results suggest a promising, simple, community-based intervention that can be prescribed to patients in family practice settings,” Dr. Tudiver said.

ORLANDO, FLA. — Consistent, moderate exercise can significantly improve the severity of restless legs syndrome symptoms without medication, a study has shown.

Despite evidence that lifestyle factors play an important role in RLS, “virtually all research studies have focused on pharmacologic therapies,” Fred Tudiver, M.D., said at the annual meeting of the North American Primary Care Research Group.

Dr. Tudiver and colleagues at East Tennessee State University in Johnson City randomized 11 of 28 patients to a reconditioning exercise program; the remaining 17 received no intervention. The intervention included 12 weeks of light- to moderate-intensity aerobic and muscular strength training three times per week.

Patients in the study—all of whom were at least 18 years old (average age 53) and had a diagnosis of RLS—were recruited from a community-based family medicine teaching center and a hospital-based wellness center. Exclusion criteria were anemia, any orthopedic condition that limited ambulation, any coronary event in the previous 6 months, uncontrolled hypertension, and current use of medication for RLS.

Before and after the intervention, patients completed the International Restless Legs Syndrome Study Group Rating Scale, a questionnaire that assessed symptom frequency and severity on a scale of 0–40.

At baseline, patients in both groups did not differ significantly in their RLS severity scores. After the 12-week intervention, however, median scores for patients in the exercise group had improved from 20.6 to 13.1, while median scores for patients in the control group went from 22.5 to 21.5.

“The results suggest a promising, simple, community-based intervention that can be prescribed to patients in family practice settings,” Dr. Tudiver said.