Mary Ann Moon

All hormone therapy—regardless of the formulation, estrogen dose, progestin type, dose regimen, route of administration, or duration of use—appears to raise the risk of ovarian cancer, according to a report.

If the association between HT and ovarian cancer proves to be causal, it would mean that as many as 5% of such malignancies could be attributable to the treatment. “Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use [HT],” said Lina Steinrud Mørch of Copenhagen University and her associates (JAMA 2009;302:298–305)

They assessed ovarian cancer using data from the Danish Sex Hormone Register Study, a national 10-year cohort study of nearly 1 million Danish women. Ms. Mørch and her colleagues restricted their analysis to the 909,946 women who were perimenopausal or postmenopausal at baseline in 1995. This included 575,883 women who had never used HT and 334,063 who had. Among the current users of HT, nearly half had been taking the hormones for more than 7 years.

A total of 3,068 incident ovarian cancers developed during the study period, including 2,681 that were epithelial tumors. Compared with women who had never taken HT, those who had showed a relative increase of 30%-58% in their risk of developing ovarian cancer, according to Ms. Mørch and her colleagues. The risk did not differ significantly by duration of use, with women who took HT for up to 4 years showing similarly increased risk as those who took it for 5 years or more. Similarly, women who took estrogen alone had approximately the same risk as did those who took combined estrogen plus progestin.

Women who took cyclic HT had increased risk similar to that in women who took continuous HT. And ovarian cancer risk was elevated regardless of HT dosage and whether HT was delivered by oral tablet, patch, or gel.

“If the difference in risk between never users and current users is due to hormone therapy, these results imply that use of HT resulted in about 1 extra case of ovarian cancer for roughly every 8,300 women taking HT each year,” the investigators wrote.

In commenting on the study, Dr. Wulf Utian, executive director of the North American Menopause Society, said, “The possibility of a very slight increase in ovarian cancer risk [with HT] should be added to the risk-benefit discussion” between the doctor and the patient. Women who have severe vasomotor symptoms negatively affecting their quality of life are likely to take the risk, he added.

Although Dr. Utian said the Scandinavian figures are probably “as reliable as you can get in a public health system,” he said the investigators included in the progestin category drugs that are not progestins such as cyproterone acetate, an antiandrogen, and raloxifene, a selective estrogen receptor modulator (SERM).

“What they've got here is fruit salad. They've got all different kinds of products lumped together, and they haven't adequately broken them out,” he said. Of the progestins that were specified, norethisterone acetate, the one most widely used in the study, was significantly associated with an increased risk of ovarian cancer; however, medroxyprogesterone acetate and levonorgestrel were not associated with an increased risk of ovarian cancer.

In addition, the investigators did not specify the type of estrogen used in their study, he noted. This contrasts with the Women's Health Initiative, a randomized, controlled study that found that Premarin (conjugated estrogens) does not increase ovarian cancer risk.

Dr. Utian reported no conflicts of interest relevant to the European drugs used in the study, but said he has consulted for several pharmaceutical companies that make estrogen products, including transdermal estrogen and SERMs. Ms. Mørch reported no conflicts of interest. Dr. Øjvind Lidegaard, an associate in the Danish study, reported receiving a grant from Schering AG, Berlin, to cover research expenses and has received fees for speeches from Schering Denmark and Novo Nordisk.

Felicia Rosenblatt Black contributed to this report.

'They've got all different kinds of products lumped together, and they haven't adequately broken them out.'

Source DR. UTIAN

All hormone therapy—regardless of the formulation, estrogen dose, progestin type, dose regimen, route of administration, or duration of use—appears to raise the risk of ovarian cancer, according to a report.

If the association between HT and ovarian cancer proves to be causal, it would mean that as many as 5% of such malignancies could be attributable to the treatment. “Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use [HT],” said Lina Steinrud Mørch of Copenhagen University and her associates (JAMA 2009;302:298–305)

They assessed ovarian cancer using data from the Danish Sex Hormone Register Study, a national 10-year cohort study of nearly 1 million Danish women. Ms. Mørch and her colleagues restricted their analysis to the 909,946 women who were perimenopausal or postmenopausal at baseline in 1995. This included 575,883 women who had never used HT and 334,063 who had. Among the current users of HT, nearly half had been taking the hormones for more than 7 years.

A total of 3,068 incident ovarian cancers developed during the study period, including 2,681 that were epithelial tumors. Compared with women who had never taken HT, those who had showed a relative increase of 30%-58% in their risk of developing ovarian cancer, according to Ms. Mørch and her colleagues. The risk did not differ significantly by duration of use, with women who took HT for up to 4 years showing similarly increased risk as those who took it for 5 years or more. Similarly, women who took estrogen alone had approximately the same risk as did those who took combined estrogen plus progestin.

Women who took cyclic HT had increased risk similar to that in women who took continuous HT. And ovarian cancer risk was elevated regardless of HT dosage and whether HT was delivered by oral tablet, patch, or gel.

“If the difference in risk between never users and current users is due to hormone therapy, these results imply that use of HT resulted in about 1 extra case of ovarian cancer for roughly every 8,300 women taking HT each year,” the investigators wrote.

In commenting on the study, Dr. Wulf Utian, executive director of the North American Menopause Society, said, “The possibility of a very slight increase in ovarian cancer risk [with HT] should be added to the risk-benefit discussion” between the doctor and the patient. Women who have severe vasomotor symptoms negatively affecting their quality of life are likely to take the risk, he added.

Although Dr. Utian said the Scandinavian figures are probably “as reliable as you can get in a public health system,” he said the investigators included in the progestin category drugs that are not progestins such as cyproterone acetate, an antiandrogen, and raloxifene, a selective estrogen receptor modulator (SERM).

“What they've got here is fruit salad. They've got all different kinds of products lumped together, and they haven't adequately broken them out,” he said. Of the progestins that were specified, norethisterone acetate, the one most widely used in the study, was significantly associated with an increased risk of ovarian cancer; however, medroxyprogesterone acetate and levonorgestrel were not associated with an increased risk of ovarian cancer.

In addition, the investigators did not specify the type of estrogen used in their study, he noted. This contrasts with the Women's Health Initiative, a randomized, controlled study that found that Premarin (conjugated estrogens) does not increase ovarian cancer risk.

Dr. Utian reported no conflicts of interest relevant to the European drugs used in the study, but said he has consulted for several pharmaceutical companies that make estrogen products, including transdermal estrogen and SERMs. Ms. Mørch reported no conflicts of interest. Dr. Øjvind Lidegaard, an associate in the Danish study, reported receiving a grant from Schering AG, Berlin, to cover research expenses and has received fees for speeches from Schering Denmark and Novo Nordisk.

Felicia Rosenblatt Black contributed to this report.

'They've got all different kinds of products lumped together, and they haven't adequately broken them out.'

Source DR. UTIAN

All hormone therapy—regardless of the formulation, estrogen dose, progestin type, dose regimen, route of administration, or duration of use—appears to raise the risk of ovarian cancer, according to a report.

If the association between HT and ovarian cancer proves to be causal, it would mean that as many as 5% of such malignancies could be attributable to the treatment. “Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use [HT],” said Lina Steinrud Mørch of Copenhagen University and her associates (JAMA 2009;302:298–305)

They assessed ovarian cancer using data from the Danish Sex Hormone Register Study, a national 10-year cohort study of nearly 1 million Danish women. Ms. Mørch and her colleagues restricted their analysis to the 909,946 women who were perimenopausal or postmenopausal at baseline in 1995. This included 575,883 women who had never used HT and 334,063 who had. Among the current users of HT, nearly half had been taking the hormones for more than 7 years.

A total of 3,068 incident ovarian cancers developed during the study period, including 2,681 that were epithelial tumors. Compared with women who had never taken HT, those who had showed a relative increase of 30%-58% in their risk of developing ovarian cancer, according to Ms. Mørch and her colleagues. The risk did not differ significantly by duration of use, with women who took HT for up to 4 years showing similarly increased risk as those who took it for 5 years or more. Similarly, women who took estrogen alone had approximately the same risk as did those who took combined estrogen plus progestin.

Women who took cyclic HT had increased risk similar to that in women who took continuous HT. And ovarian cancer risk was elevated regardless of HT dosage and whether HT was delivered by oral tablet, patch, or gel.

“If the difference in risk between never users and current users is due to hormone therapy, these results imply that use of HT resulted in about 1 extra case of ovarian cancer for roughly every 8,300 women taking HT each year,” the investigators wrote.

In commenting on the study, Dr. Wulf Utian, executive director of the North American Menopause Society, said, “The possibility of a very slight increase in ovarian cancer risk [with HT] should be added to the risk-benefit discussion” between the doctor and the patient. Women who have severe vasomotor symptoms negatively affecting their quality of life are likely to take the risk, he added.

Although Dr. Utian said the Scandinavian figures are probably “as reliable as you can get in a public health system,” he said the investigators included in the progestin category drugs that are not progestins such as cyproterone acetate, an antiandrogen, and raloxifene, a selective estrogen receptor modulator (SERM).

“What they've got here is fruit salad. They've got all different kinds of products lumped together, and they haven't adequately broken them out,” he said. Of the progestins that were specified, norethisterone acetate, the one most widely used in the study, was significantly associated with an increased risk of ovarian cancer; however, medroxyprogesterone acetate and levonorgestrel were not associated with an increased risk of ovarian cancer.

In addition, the investigators did not specify the type of estrogen used in their study, he noted. This contrasts with the Women's Health Initiative, a randomized, controlled study that found that Premarin (conjugated estrogens) does not increase ovarian cancer risk.

Dr. Utian reported no conflicts of interest relevant to the European drugs used in the study, but said he has consulted for several pharmaceutical companies that make estrogen products, including transdermal estrogen and SERMs. Ms. Mørch reported no conflicts of interest. Dr. Øjvind Lidegaard, an associate in the Danish study, reported receiving a grant from Schering AG, Berlin, to cover research expenses and has received fees for speeches from Schering Denmark and Novo Nordisk.

Felicia Rosenblatt Black contributed to this report.

'They've got all different kinds of products lumped together, and they haven't adequately broken them out.'

Source DR. UTIAN

All hormone therapy—regardless of the formulation, estrogen dose, progestin type, dose regimen, route of administration, or duration of use—appears to raise the risk of ovarian cancer, according to a report.

If the association between HT and ovarian cancer proves to be causal, it would mean that as many as 5% of such malignancies could be attributable to the treatment. “Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use [HT],” said Lina Steinrud Mørch of Copenhagen University and her associates.

They assessed ovarian cancer using data from the Danish Sex Hormone Register Study, a national 10-year cohort study of nearly 1 million Danish women. Ms. Mørch and her colleagues restricted their analysis to the 909,946 women who were perimenopausal or postmenopausal at baseline in 1995.

This included 575,883 women who had never used HT and 334,063 who had. Among the current users of HT, nearly half had been taking the hormones for more than 7 years.

A total of 3,068 incident ovarian cancers developed in the study period, including 2,681 that were epithelial tumors.

Compared with women who had never taken HT, those who had showed a relative increase of 30%-58% in their risk of developing ovarian cancer, according to Ms. Mørch and her colleagues (JAMA 2009;302:298-305).

The risk did not differ significantly by duration of use, with women who took HT for up to 4 years showing similarly increased risk as those who took it for 5 years or more. Similarly, women who took estrogen alone had about the same risk as did those who took combined estrogen plus progestin.

Women who took cyclic HT had increased risk similar to that in women who took continuous HT. And ovarian cancer risk was elevated regardless of HT dosage and regardless of whether HT was delivered by oral tablet, patch, or gel.

“If the difference in risk between never users and current users is due to hormone therapy, these results imply that use of HT resulted in about 1 extra case of ovarian cancer for roughly every 8,300 women taking HT each year,” the investigators wrote.

In commenting on the study, Dr. Wulf H. Utian, executive director of the North American Menopause Society, said, “The possibility of a very slight increase in ovarian cancer risk [with HT] should be added to the risk-benefit discussion” between physicians and patients. Women who have severe vasomotor symptoms negatively affecting their quality of life are likely to take the risk, he added.

Although Dr. Utian said the Scandinavian figures are probably “as reliable as you can get in a public health system,” he said he had concerns about the study's methodology. In evaluating different HT regimens, the investigators included in the progestin category drugs that are not progestins such as cyproterone acetate, an antiandrogen, and raloxifene, a selective estrogen receptor modulator (SERM).

“What they've got here is fruit salad. They've got all different kinds of products lumped together, and they haven't adequately broken them out,” he said. Of the progestins that were specified, norethisterone acetate, the one most widely used in the study, was significantly associated with an increased risk of ovarian cancer; however, medroxyprogesterone acetate and levonorgestrel were not associated with an increased risk of ovarian cancer.

In addition, the investigators did not specify the type of estrogen used in their study, he noted. This contrasts with the Women's Health Initiative, a randomized, controlled study that found that Premarin (conjugated estrogens) does not increase ovarian cancer risk. The conjugated estrogen formulation is not used in Denmark, he said, so it's unlikely that it was part of the current study.

Dr. Utian reported no conflicts of interest relevant to the European drugs used in the study, but said he has consulted for several pharmaceutical companies that make estrogen products, including transdermal estrogen and SERMs. He reported being an investigator in a study of a SERM manufactured by Wyeth Pharmaceuticals.

Ms. Mørch reported no conflicts of interest. Dr. Øjvind Lidegaard, an associate in the Danish study, reported receiving a grant from Schering AG, Berlin, to cover research expenses and has received fees for speeches from Schering Denmark and Novo Nordisk. This study was supported by a grant from the Danish Cancer Society.

Felicia Rosenblatt Black contributed to this report.

'What they've got here is fruit salad. They've got all different kinds of products lumped together.'

Source DR. UTIAN

All hormone therapy—regardless of the formulation, estrogen dose, progestin type, dose regimen, route of administration, or duration of use—appears to raise the risk of ovarian cancer, according to a report.

If the association between HT and ovarian cancer proves to be causal, it would mean that as many as 5% of such malignancies could be attributable to the treatment. “Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use [HT],” said Lina Steinrud Mørch of Copenhagen University and her associates.

They assessed ovarian cancer using data from the Danish Sex Hormone Register Study, a national 10-year cohort study of nearly 1 million Danish women. Ms. Mørch and her colleagues restricted their analysis to the 909,946 women who were perimenopausal or postmenopausal at baseline in 1995.

This included 575,883 women who had never used HT and 334,063 who had. Among the current users of HT, nearly half had been taking the hormones for more than 7 years.

A total of 3,068 incident ovarian cancers developed in the study period, including 2,681 that were epithelial tumors.

Compared with women who had never taken HT, those who had showed a relative increase of 30%-58% in their risk of developing ovarian cancer, according to Ms. Mørch and her colleagues (JAMA 2009;302:298-305).

The risk did not differ significantly by duration of use, with women who took HT for up to 4 years showing similarly increased risk as those who took it for 5 years or more. Similarly, women who took estrogen alone had about the same risk as did those who took combined estrogen plus progestin.

Women who took cyclic HT had increased risk similar to that in women who took continuous HT. And ovarian cancer risk was elevated regardless of HT dosage and regardless of whether HT was delivered by oral tablet, patch, or gel.

“If the difference in risk between never users and current users is due to hormone therapy, these results imply that use of HT resulted in about 1 extra case of ovarian cancer for roughly every 8,300 women taking HT each year,” the investigators wrote.

In commenting on the study, Dr. Wulf H. Utian, executive director of the North American Menopause Society, said, “The possibility of a very slight increase in ovarian cancer risk [with HT] should be added to the risk-benefit discussion” between physicians and patients. Women who have severe vasomotor symptoms negatively affecting their quality of life are likely to take the risk, he added.

Although Dr. Utian said the Scandinavian figures are probably “as reliable as you can get in a public health system,” he said he had concerns about the study's methodology. In evaluating different HT regimens, the investigators included in the progestin category drugs that are not progestins such as cyproterone acetate, an antiandrogen, and raloxifene, a selective estrogen receptor modulator (SERM).

“What they've got here is fruit salad. They've got all different kinds of products lumped together, and they haven't adequately broken them out,” he said. Of the progestins that were specified, norethisterone acetate, the one most widely used in the study, was significantly associated with an increased risk of ovarian cancer; however, medroxyprogesterone acetate and levonorgestrel were not associated with an increased risk of ovarian cancer.

In addition, the investigators did not specify the type of estrogen used in their study, he noted. This contrasts with the Women's Health Initiative, a randomized, controlled study that found that Premarin (conjugated estrogens) does not increase ovarian cancer risk. The conjugated estrogen formulation is not used in Denmark, he said, so it's unlikely that it was part of the current study.

Dr. Utian reported no conflicts of interest relevant to the European drugs used in the study, but said he has consulted for several pharmaceutical companies that make estrogen products, including transdermal estrogen and SERMs. He reported being an investigator in a study of a SERM manufactured by Wyeth Pharmaceuticals.

Ms. Mørch reported no conflicts of interest. Dr. Øjvind Lidegaard, an associate in the Danish study, reported receiving a grant from Schering AG, Berlin, to cover research expenses and has received fees for speeches from Schering Denmark and Novo Nordisk. This study was supported by a grant from the Danish Cancer Society.

Felicia Rosenblatt Black contributed to this report.

'What they've got here is fruit salad. They've got all different kinds of products lumped together.'

Source DR. UTIAN

All hormone therapy—regardless of the formulation, estrogen dose, progestin type, dose regimen, route of administration, or duration of use—appears to raise the risk of ovarian cancer, according to a report.

If the association between HT and ovarian cancer proves to be causal, it would mean that as many as 5% of such malignancies could be attributable to the treatment. “Even though this share seems low, ovarian cancer remains highly fatal, so accordingly this risk warrants consideration when deciding whether to use [HT],” said Lina Steinrud Mørch of Copenhagen University and her associates.

They assessed ovarian cancer using data from the Danish Sex Hormone Register Study, a national 10-year cohort study of nearly 1 million Danish women. Ms. Mørch and her colleagues restricted their analysis to the 909,946 women who were perimenopausal or postmenopausal at baseline in 1995.

This included 575,883 women who had never used HT and 334,063 who had. Among the current users of HT, nearly half had been taking the hormones for more than 7 years.

A total of 3,068 incident ovarian cancers developed in the study period, including 2,681 that were epithelial tumors.

Compared with women who had never taken HT, those who had showed a relative increase of 30%-58% in their risk of developing ovarian cancer, according to Ms. Mørch and her colleagues (JAMA 2009;302:298-305).

The risk did not differ significantly by duration of use, with women who took HT for up to 4 years showing similarly increased risk as those who took it for 5 years or more. Similarly, women who took estrogen alone had about the same risk as did those who took combined estrogen plus progestin.

Women who took cyclic HT had increased risk similar to that in women who took continuous HT. And ovarian cancer risk was elevated regardless of HT dosage and regardless of whether HT was delivered by oral tablet, patch, or gel.

“If the difference in risk between never users and current users is due to hormone therapy, these results imply that use of HT resulted in about 1 extra case of ovarian cancer for roughly every 8,300 women taking HT each year,” the investigators wrote.

In commenting on the study, Dr. Wulf H. Utian, executive director of the North American Menopause Society, said, “The possibility of a very slight increase in ovarian cancer risk [with HT] should be added to the risk-benefit discussion” between physicians and patients. Women who have severe vasomotor symptoms negatively affecting their quality of life are likely to take the risk, he added.

Although Dr. Utian said the Scandinavian figures are probably “as reliable as you can get in a public health system,” he said he had concerns about the study's methodology. In evaluating different HT regimens, the investigators included in the progestin category drugs that are not progestins such as cyproterone acetate, an antiandrogen, and raloxifene, a selective estrogen receptor modulator (SERM).

“What they've got here is fruit salad. They've got all different kinds of products lumped together, and they haven't adequately broken them out,” he said. Of the progestins that were specified, norethisterone acetate, the one most widely used in the study, was significantly associated with an increased risk of ovarian cancer; however, medroxyprogesterone acetate and levonorgestrel were not associated with an increased risk of ovarian cancer.

In addition, the investigators did not specify the type of estrogen used in their study, he noted. This contrasts with the Women's Health Initiative, a randomized, controlled study that found that Premarin (conjugated estrogens) does not increase ovarian cancer risk. The conjugated estrogen formulation is not used in Denmark, he said, so it's unlikely that it was part of the current study.

Dr. Utian reported no conflicts of interest relevant to the European drugs used in the study, but said he has consulted for several pharmaceutical companies that make estrogen products, including transdermal estrogen and SERMs. He reported being an investigator in a study of a SERM manufactured by Wyeth Pharmaceuticals.

Ms. Mørch reported no conflicts of interest. Dr. Øjvind Lidegaard, an associate in the Danish study, reported receiving a grant from Schering AG, Berlin, to cover research expenses and has received fees for speeches from Schering Denmark and Novo Nordisk. This study was supported by a grant from the Danish Cancer Society.

Felicia Rosenblatt Black contributed to this report.

'What they've got here is fruit salad. They've got all different kinds of products lumped together.'

Source DR. UTIAN

The glutamate modulator N-acetylcysteine significantly reduced symptoms of trichotillomania, according to a study of 50 patients.

In what the investigators described as the first clinical trial assessing a glutamatergic agent for this disorder, N-acetylcysteine was judged effective by both patients and physicians, to a degree comparable with that achieved with other medications plus cognitive-behavioral therapy.

“N-acetylcysteine is an amino acid, is available in health-food stores, is cheaper than most insurance copayments, and seems to be well tolerated. [It] could be an effective treatment option for people with trichotillomania,” said Dr. Jon E. Grant and his associates at the University of Minnesota, Minneapolis.

Moreover, the study results indicate that “pharmacologic manipulation of the glutamate system [in the nucleus accumbens] may target core symptoms of compulsive behaviors,” they added.

Trichotillomania is the recurrent pulling out of hair—head hair, eyebrows, eyelashes, pubic hair, or other body hair—to obtain relief of tension, which leads to noticeable hair loss. There is no Food and Drug Administration-approved treatment for trichotillomania at present, but glutamatergic dysfunction has been implicated in the pathogenesis of disorders that have a compulsive component, and glutamate modulators like N-acetylcysteine have been used to treat cocaine urges and gambling behavior.

Dr. Grant and his colleagues assessed the agent in 45 women and 5 men (mean age, 34 years) who reported spending a mean of 65 minutes every day pulling out hair, usually from multiple sites. Most of these patients had never sought mental health treatment for hair pulling.

Thirty of the study subjects (60%) reported having at least one clinically important comorbid disorder, such as major depressive disorder; an anxiety disorder; another impulse-control disorder, such as skin picking or nail biting; or an eating disorder. Four patients were receiving psychotherapy, and 28 were taking a psychotropic medication, including a selective serotonin reuptake inhibitor or a selective serotonin norepinephrine inhibitor, or a stimulant.

The study subjects were randomly assigned to receive 12 weeks of N-acetylcysteine or a matching placebo. A significant treatment effect was evident at 9 weeks and persisted for the duration of the study.

At the conclusion of treatment, those who had taken N-acetylcysteine showed significant improvement on both the severity subscale and the “resistance and control” subscale of the Massachusetts General Hospital Hairpulling Scale, as well as on the Psychiatric Institute Trichotillomania Scale.

A total of 56% of those in the active-treatment group said they were “much” or “very much” improved on the Clinical Global Impression (CGI) scale, compared with 16% of the placebo group.

There were no adverse events reported in subjects taking active medication. A few subjects in the placebo group reported mild adverse events.

Dr. Grant has received research grants from Forest Pharmaceuticals, GlaxoSmithKline, and Somaxon Pharmaceuticals and has served as a consultant to Pfizer Pharmaceuticals and Somaxon. In addition, Dr. Grant, who also is a lawyer, has consulted for law offices as an expert regarding impulse control disorders.

This patient extracted most of the hair from a wide area of the scalp.

Source ©Elsevier 2004, Habif: Clinical Dermatology, 4th ed.

The glutamate modulator N-acetylcysteine significantly reduced symptoms of trichotillomania, according to a study of 50 patients.

In what the investigators described as the first clinical trial assessing a glutamatergic agent for this disorder, N-acetylcysteine was judged effective by both patients and physicians, to a degree comparable with that achieved with other medications plus cognitive-behavioral therapy.

“N-acetylcysteine is an amino acid, is available in health-food stores, is cheaper than most insurance copayments, and seems to be well tolerated. [It] could be an effective treatment option for people with trichotillomania,” said Dr. Jon E. Grant and his associates at the University of Minnesota, Minneapolis.

Moreover, the study results indicate that “pharmacologic manipulation of the glutamate system [in the nucleus accumbens] may target core symptoms of compulsive behaviors,” they added.

Trichotillomania is the recurrent pulling out of hair—head hair, eyebrows, eyelashes, pubic hair, or other body hair—to obtain relief of tension, which leads to noticeable hair loss. There is no Food and Drug Administration-approved treatment for trichotillomania at present, but glutamatergic dysfunction has been implicated in the pathogenesis of disorders that have a compulsive component, and glutamate modulators like N-acetylcysteine have been used to treat cocaine urges and gambling behavior.

Dr. Grant and his colleagues assessed the agent in 45 women and 5 men (mean age, 34 years) who reported spending a mean of 65 minutes every day pulling out hair, usually from multiple sites. Most of these patients had never sought mental health treatment for hair pulling.

Thirty of the study subjects (60%) reported having at least one clinically important comorbid disorder, such as major depressive disorder; an anxiety disorder; another impulse-control disorder, such as skin picking or nail biting; or an eating disorder. Four patients were receiving psychotherapy, and 28 were taking a psychotropic medication, including a selective serotonin reuptake inhibitor or a selective serotonin norepinephrine inhibitor, or a stimulant.

The study subjects were randomly assigned to receive 12 weeks of N-acetylcysteine or a matching placebo. A significant treatment effect was evident at 9 weeks and persisted for the duration of the study.

At the conclusion of treatment, those who had taken N-acetylcysteine showed significant improvement on both the severity subscale and the “resistance and control” subscale of the Massachusetts General Hospital Hairpulling Scale, as well as on the Psychiatric Institute Trichotillomania Scale.

A total of 56% of those in the active-treatment group said they were “much” or “very much” improved on the Clinical Global Impression (CGI) scale, compared with 16% of the placebo group.

There were no adverse events reported in subjects taking active medication. A few subjects in the placebo group reported mild adverse events.

Dr. Grant has received research grants from Forest Pharmaceuticals, GlaxoSmithKline, and Somaxon Pharmaceuticals and has served as a consultant to Pfizer Pharmaceuticals and Somaxon. In addition, Dr. Grant, who also is a lawyer, has consulted for law offices as an expert regarding impulse control disorders.

This patient extracted most of the hair from a wide area of the scalp.

Source ©Elsevier 2004, Habif: Clinical Dermatology, 4th ed.

The glutamate modulator N-acetylcysteine significantly reduced symptoms of trichotillomania, according to a study of 50 patients.

In what the investigators described as the first clinical trial assessing a glutamatergic agent for this disorder, N-acetylcysteine was judged effective by both patients and physicians, to a degree comparable with that achieved with other medications plus cognitive-behavioral therapy.

“N-acetylcysteine is an amino acid, is available in health-food stores, is cheaper than most insurance copayments, and seems to be well tolerated. [It] could be an effective treatment option for people with trichotillomania,” said Dr. Jon E. Grant and his associates at the University of Minnesota, Minneapolis.

Moreover, the study results indicate that “pharmacologic manipulation of the glutamate system [in the nucleus accumbens] may target core symptoms of compulsive behaviors,” they added.

Trichotillomania is the recurrent pulling out of hair—head hair, eyebrows, eyelashes, pubic hair, or other body hair—to obtain relief of tension, which leads to noticeable hair loss. There is no Food and Drug Administration-approved treatment for trichotillomania at present, but glutamatergic dysfunction has been implicated in the pathogenesis of disorders that have a compulsive component, and glutamate modulators like N-acetylcysteine have been used to treat cocaine urges and gambling behavior.

Dr. Grant and his colleagues assessed the agent in 45 women and 5 men (mean age, 34 years) who reported spending a mean of 65 minutes every day pulling out hair, usually from multiple sites. Most of these patients had never sought mental health treatment for hair pulling.

Thirty of the study subjects (60%) reported having at least one clinically important comorbid disorder, such as major depressive disorder; an anxiety disorder; another impulse-control disorder, such as skin picking or nail biting; or an eating disorder. Four patients were receiving psychotherapy, and 28 were taking a psychotropic medication, including a selective serotonin reuptake inhibitor or a selective serotonin norepinephrine inhibitor, or a stimulant.

The study subjects were randomly assigned to receive 12 weeks of N-acetylcysteine or a matching placebo. A significant treatment effect was evident at 9 weeks and persisted for the duration of the study.

At the conclusion of treatment, those who had taken N-acetylcysteine showed significant improvement on both the severity subscale and the “resistance and control” subscale of the Massachusetts General Hospital Hairpulling Scale, as well as on the Psychiatric Institute Trichotillomania Scale.

A total of 56% of those in the active-treatment group said they were “much” or “very much” improved on the Clinical Global Impression (CGI) scale, compared with 16% of the placebo group.

There were no adverse events reported in subjects taking active medication. A few subjects in the placebo group reported mild adverse events.

Dr. Grant has received research grants from Forest Pharmaceuticals, GlaxoSmithKline, and Somaxon Pharmaceuticals and has served as a consultant to Pfizer Pharmaceuticals and Somaxon. In addition, Dr. Grant, who also is a lawyer, has consulted for law offices as an expert regarding impulse control disorders.

This patient extracted most of the hair from a wide area of the scalp.

Source ©Elsevier 2004, Habif: Clinical Dermatology, 4th ed.

A cognitive-behavioral intervention delivered via the Internet significantly reduced insomnia severity and contributed to overall sleep improvement in a study of 44 patients.

The 9-week intervention reduced the number of nighttime awakenings and improved sleep efficiency to a similar degree as has been reported for CBT face-to-face therapy, self-help bibliotherapy, group therapy, telephone therapy, and pharmacotherapy, said Lee M. Ritterband, Ph.D., of the University of Virginia Health System, Charlottesville, and his associates.

“An effective and inexpensive Internet intervention would expand treatment options for large numbers of adults with insomnia, especially those whose geographical location prohibits access to relevant care, and could be a substantive first-line treatment choice,” they noted (Arch. Gen. Psychiatry 2009;66:692-8).

Although traditional CBT is one of the most effective treatments for insomnia, its availability is “severely limited,” in part because of a lack of trained clinicians, the uneven geographical distribution of trained clinicians, and the cost of treatment. Dr. Ritterband and his colleagues assessed the feasibility and efficacy of a fully automated Internet-based intervention called SHUTi (Sleep Healthy Using the Internet).

SHUTi provides instruction on going to bed only when sleepy, getting out of bed when unable to sleep, and returning only when sleep is imminent. The program advises patients to avoid sleep-incompatible activities in the bedroom such as watching television, to forgo daytime napping, and to arise at the same hour every day. Patients also are instructed to improve their sleep hygiene by avoiding nicotine, caffeine, and alcohol before bedtime.

The SHUTi intervention also addresses “unhelpful” beliefs and thoughts, such as the notion that people absolutely need 8 hours of sleep every night or excessive concern about the consequences of insomnia.

Participants fill out the Insomnia Severity Index (ISI) online and complete weekly sleep diaries. That information is then used to individually tailor recommendations for the coming week, all of which is computed automatically using algorithms that were developed specifically for SHUTi, Dr. Ritterband and his colleagues said.

They compared insomnia outcomes between 22 insomnia patients randomly assigned to the SHUTi intervention and 22 control patients who were wait-listed to participate in the program. The mean age of participants was 45 years; they had had sleep problems for an average of more than 10 years, and at the time of enrollment they reported disruptive sleep more than 5 nights per week.

The intervention group showed marked improvement in insomnia severity at the conclusion of the program as well as 6 months later, while the control group showed little change. Sixteen of the intervention subjects (73%) were judged to be in remission by ISI score, compared with none of the control subjects.

“It is important to highlight that the treatment effect sizes found using this Internet intervention, which was delivered with no human support and at a relatively low cost, are comparable to those found in face-to-face studies,” the investigators said.

No relevant conflicts of interest were reported.

The SHUTi intervention provides instruction on going to bed only when sleepy and getting out of bed when unable to sleep.

Source ©Karen Winton/iStockphoto.com

A cognitive-behavioral intervention delivered via the Internet significantly reduced insomnia severity and contributed to overall sleep improvement in a study of 44 patients.

The 9-week intervention reduced the number of nighttime awakenings and improved sleep efficiency to a similar degree as has been reported for CBT face-to-face therapy, self-help bibliotherapy, group therapy, telephone therapy, and pharmacotherapy, said Lee M. Ritterband, Ph.D., of the University of Virginia Health System, Charlottesville, and his associates.

“An effective and inexpensive Internet intervention would expand treatment options for large numbers of adults with insomnia, especially those whose geographical location prohibits access to relevant care, and could be a substantive first-line treatment choice,” they noted (Arch. Gen. Psychiatry 2009;66:692-8).

Although traditional CBT is one of the most effective treatments for insomnia, its availability is “severely limited,” in part because of a lack of trained clinicians, the uneven geographical distribution of trained clinicians, and the cost of treatment. Dr. Ritterband and his colleagues assessed the feasibility and efficacy of a fully automated Internet-based intervention called SHUTi (Sleep Healthy Using the Internet).

SHUTi provides instruction on going to bed only when sleepy, getting out of bed when unable to sleep, and returning only when sleep is imminent. The program advises patients to avoid sleep-incompatible activities in the bedroom such as watching television, to forgo daytime napping, and to arise at the same hour every day. Patients also are instructed to improve their sleep hygiene by avoiding nicotine, caffeine, and alcohol before bedtime.

The SHUTi intervention also addresses “unhelpful” beliefs and thoughts, such as the notion that people absolutely need 8 hours of sleep every night or excessive concern about the consequences of insomnia.

Participants fill out the Insomnia Severity Index (ISI) online and complete weekly sleep diaries. That information is then used to individually tailor recommendations for the coming week, all of which is computed automatically using algorithms that were developed specifically for SHUTi, Dr. Ritterband and his colleagues said.

They compared insomnia outcomes between 22 insomnia patients randomly assigned to the SHUTi intervention and 22 control patients who were wait-listed to participate in the program. The mean age of participants was 45 years; they had had sleep problems for an average of more than 10 years, and at the time of enrollment they reported disruptive sleep more than 5 nights per week.

The intervention group showed marked improvement in insomnia severity at the conclusion of the program as well as 6 months later, while the control group showed little change. Sixteen of the intervention subjects (73%) were judged to be in remission by ISI score, compared with none of the control subjects.

“It is important to highlight that the treatment effect sizes found using this Internet intervention, which was delivered with no human support and at a relatively low cost, are comparable to those found in face-to-face studies,” the investigators said.

No relevant conflicts of interest were reported.

The SHUTi intervention provides instruction on going to bed only when sleepy and getting out of bed when unable to sleep.

Source ©Karen Winton/iStockphoto.com

A cognitive-behavioral intervention delivered via the Internet significantly reduced insomnia severity and contributed to overall sleep improvement in a study of 44 patients.

The 9-week intervention reduced the number of nighttime awakenings and improved sleep efficiency to a similar degree as has been reported for CBT face-to-face therapy, self-help bibliotherapy, group therapy, telephone therapy, and pharmacotherapy, said Lee M. Ritterband, Ph.D., of the University of Virginia Health System, Charlottesville, and his associates.

“An effective and inexpensive Internet intervention would expand treatment options for large numbers of adults with insomnia, especially those whose geographical location prohibits access to relevant care, and could be a substantive first-line treatment choice,” they noted (Arch. Gen. Psychiatry 2009;66:692-8).

Although traditional CBT is one of the most effective treatments for insomnia, its availability is “severely limited,” in part because of a lack of trained clinicians, the uneven geographical distribution of trained clinicians, and the cost of treatment. Dr. Ritterband and his colleagues assessed the feasibility and efficacy of a fully automated Internet-based intervention called SHUTi (Sleep Healthy Using the Internet).

SHUTi provides instruction on going to bed only when sleepy, getting out of bed when unable to sleep, and returning only when sleep is imminent. The program advises patients to avoid sleep-incompatible activities in the bedroom such as watching television, to forgo daytime napping, and to arise at the same hour every day. Patients also are instructed to improve their sleep hygiene by avoiding nicotine, caffeine, and alcohol before bedtime.

The SHUTi intervention also addresses “unhelpful” beliefs and thoughts, such as the notion that people absolutely need 8 hours of sleep every night or excessive concern about the consequences of insomnia.

Participants fill out the Insomnia Severity Index (ISI) online and complete weekly sleep diaries. That information is then used to individually tailor recommendations for the coming week, all of which is computed automatically using algorithms that were developed specifically for SHUTi, Dr. Ritterband and his colleagues said.

They compared insomnia outcomes between 22 insomnia patients randomly assigned to the SHUTi intervention and 22 control patients who were wait-listed to participate in the program. The mean age of participants was 45 years; they had had sleep problems for an average of more than 10 years, and at the time of enrollment they reported disruptive sleep more than 5 nights per week.

The intervention group showed marked improvement in insomnia severity at the conclusion of the program as well as 6 months later, while the control group showed little change. Sixteen of the intervention subjects (73%) were judged to be in remission by ISI score, compared with none of the control subjects.

“It is important to highlight that the treatment effect sizes found using this Internet intervention, which was delivered with no human support and at a relatively low cost, are comparable to those found in face-to-face studies,” the investigators said.

No relevant conflicts of interest were reported.

The SHUTi intervention provides instruction on going to bed only when sleepy and getting out of bed when unable to sleep.

Source ©Karen Winton/iStockphoto.com

The current decline in private insurance coverage has been offset by an “enormous increase” in public coverage over the past 2 decades–an expansion that might be at an end, according to a report.

“Serious problems could lie ahead if employer-based coverage continues to decline while the availability of public coverage remains the same or is reduced,” said David M. Cutler, Ph.D., and Alexander M. Gelber, Ph.D.

Both Dr. Cutler and Dr. Gelber are affiliated with Harvard University, Boston, and the National Bureau of Economic Research. The investigators said they examined trends in insurance coverage because the net change in coverage over time has been uncertain. It is thought that Americans have been increasingly uninsured for longer periods, but “on the other hand, eligibility for public insurance has been expanded,” the authors noted.

Dr. Cutler and Dr. Gelber compared data from the U.S. Census Bureau's Survey of Income and Program Participation for the years 1983-1986 and 2001-2004.

This survey includes information on many socioeconomic variables for a random sample of 25,946 people in the first study period and 40,282 people in the second (N. Engl. J. Med. 2009;360:1740-8).

“The overall economy was better in 2001-2004 than in 1983-1986, but in each case it was in recovery from a recession,” they said.

The analysis showed that more Americans were likely to experience a period of uninsurance in the second study period (37%) than in the first (35%), in large part because more people lost private insurance.

However, intervals of uninsurance were shorter in the second study period than in the first.

For example, the percentage of people who were uninsured for 2 years or longer was lower in the second study period (20%) than it was 20 years ago (26%), the researchers said

Over the course of the study, the proportion of uninsured periods that ended when people obtained private insurance decreased by 6%, while the proportion that ended when people obtained public insurance increased by 12%, the report found.

The current decline in private insurance coverage has been offset by an “enormous increase” in public coverage over the past 2 decades–an expansion that might be at an end, according to a report.

“Serious problems could lie ahead if employer-based coverage continues to decline while the availability of public coverage remains the same or is reduced,” said David M. Cutler, Ph.D., and Alexander M. Gelber, Ph.D.

Both Dr. Cutler and Dr. Gelber are affiliated with Harvard University, Boston, and the National Bureau of Economic Research. The investigators said they examined trends in insurance coverage because the net change in coverage over time has been uncertain. It is thought that Americans have been increasingly uninsured for longer periods, but “on the other hand, eligibility for public insurance has been expanded,” the authors noted.

Dr. Cutler and Dr. Gelber compared data from the U.S. Census Bureau's Survey of Income and Program Participation for the years 1983-1986 and 2001-2004.

This survey includes information on many socioeconomic variables for a random sample of 25,946 people in the first study period and 40,282 people in the second (N. Engl. J. Med. 2009;360:1740-8).

“The overall economy was better in 2001-2004 than in 1983-1986, but in each case it was in recovery from a recession,” they said.

The analysis showed that more Americans were likely to experience a period of uninsurance in the second study period (37%) than in the first (35%), in large part because more people lost private insurance.

However, intervals of uninsurance were shorter in the second study period than in the first.

For example, the percentage of people who were uninsured for 2 years or longer was lower in the second study period (20%) than it was 20 years ago (26%), the researchers said

Over the course of the study, the proportion of uninsured periods that ended when people obtained private insurance decreased by 6%, while the proportion that ended when people obtained public insurance increased by 12%, the report found.

The current decline in private insurance coverage has been offset by an “enormous increase” in public coverage over the past 2 decades–an expansion that might be at an end, according to a report.

“Serious problems could lie ahead if employer-based coverage continues to decline while the availability of public coverage remains the same or is reduced,” said David M. Cutler, Ph.D., and Alexander M. Gelber, Ph.D.

Both Dr. Cutler and Dr. Gelber are affiliated with Harvard University, Boston, and the National Bureau of Economic Research. The investigators said they examined trends in insurance coverage because the net change in coverage over time has been uncertain. It is thought that Americans have been increasingly uninsured for longer periods, but “on the other hand, eligibility for public insurance has been expanded,” the authors noted.

Dr. Cutler and Dr. Gelber compared data from the U.S. Census Bureau's Survey of Income and Program Participation for the years 1983-1986 and 2001-2004.

This survey includes information on many socioeconomic variables for a random sample of 25,946 people in the first study period and 40,282 people in the second (N. Engl. J. Med. 2009;360:1740-8).

“The overall economy was better in 2001-2004 than in 1983-1986, but in each case it was in recovery from a recession,” they said.

The analysis showed that more Americans were likely to experience a period of uninsurance in the second study period (37%) than in the first (35%), in large part because more people lost private insurance.

However, intervals of uninsurance were shorter in the second study period than in the first.

For example, the percentage of people who were uninsured for 2 years or longer was lower in the second study period (20%) than it was 20 years ago (26%), the researchers said

Over the course of the study, the proportion of uninsured periods that ended when people obtained private insurance decreased by 6%, while the proportion that ended when people obtained public insurance increased by 12%, the report found.

A cognitive-behavioral therapy intervention delivered via the Internet significantly reduced insomnia severity and contributed to overall sleep improvement in a study of 44 adults, according to a report in the Archives of General Psychiatry.

The 9-week intervention reduced the number of nighttime awakenings and improved sleep efficiency to a similar degree as has been reported for face-to-face CBT, self-help bibliotherapy, group therapy, telephone therapy, and pharmacotherapy, said Lee M. Ritterband, Ph.D., of the University of Virginia Health System, Charlottesville, and his associates.

“An effective and inexpensive Internet intervention would expand treatment options for large numbers of adults with insomnia, especially those whose geographical location prohibits access to relevant care, and could be a substantive first-line treatment choice,” they noted. Although traditional CBT is one of the most effective treatments for insomnia, its availability is “severely limited,” in part because of a lack of trained clinicians, the uneven geographical distribution of trained clinicians, and the cost of treatment.

Dr. Ritterband and his colleagues assessed the feasibility and efficacy of a fully automated Internet-based intervention called SHUTi (Sleep Healthy Using the Internet).

SHUTi provides instruction on going to bed only when sleepy, getting out of bed when unable to sleep, and returning only when sleep is imminent. The program advises patients to avoid sleep-incompatible activities in the bedroom such as watching television, to forgo daytime napping, and to arise at the same hour every day. Patients also are instructed to improve their sleep hygiene by avoiding nicotine, caffeine, and alcohol before bedtime. SHUTi also addresses “unhelpful” beliefs and thoughts, such as the notion that people absolutely need 8 hours of sleep every night or excessive concern about the consequences of insomnia.

Participants fill out the Insomnia Severity Index (ISI) online and complete weekly sleep diaries. That information is then used to individually tailor recommendations for the coming week, all of which is computed automatically using algorithms developed specifically for SHUTi.

The intervention uses graphics and animation as well as text, and it includes quizzes, brief games, and vignettes to deliver information, Dr. Ritterband and his colleagues said (Arch. Gen. Psychiatry 2009;66:692-8).

They compared insomnia outcomes between 22 insomnia patients randomly assigned to the SHUTi intervention and 22 control patients who were wait-listed to participate in the program.

The mean age of participants was 45 years; they had had sleep problems for an average of more than 10 years, and at the time of enrollment they reported disruptive sleep more than 5 nights per week.

The intervention group showed marked improvement in insomnia severity at the conclusion of the program as well as 6 months later, while the control group showed little change. Sixteen of the intervention subjects (73%) were judged to be in remission by ISI score, compared with none of the control subjects.

“It is important to highlight that the treatment effect sizes found using this Internet intervention, which was delivered with no human support and at a relatively low cost, are comparable to those found in face-to-face studies,” the investigators said.

They also pointed out that this intervention might expand treatment options for adults whose geographical location prohibits access to care.

However, Dr. Ritterband and his colleagues added that their study sample was “small, relatively homogeneous, well educated, and restricted to individuals with primary insomnia and no comorbidities. Future studies should enroll larger and more heterogeneous samples to improve the generalizability of the findings.”

No relevant conflicts of interest were reported. The study was supported by a grant from the National Institute of Mental Health, National Institutes of Health.

The Sleep Healthy Using the Internet (SHUTi) intervention advises patients to arise at the same hour every day.

Source ©Karen Winton/iStockphoto.com

A cognitive-behavioral therapy intervention delivered via the Internet significantly reduced insomnia severity and contributed to overall sleep improvement in a study of 44 adults, according to a report in the Archives of General Psychiatry.

The 9-week intervention reduced the number of nighttime awakenings and improved sleep efficiency to a similar degree as has been reported for face-to-face CBT, self-help bibliotherapy, group therapy, telephone therapy, and pharmacotherapy, said Lee M. Ritterband, Ph.D., of the University of Virginia Health System, Charlottesville, and his associates.

“An effective and inexpensive Internet intervention would expand treatment options for large numbers of adults with insomnia, especially those whose geographical location prohibits access to relevant care, and could be a substantive first-line treatment choice,” they noted. Although traditional CBT is one of the most effective treatments for insomnia, its availability is “severely limited,” in part because of a lack of trained clinicians, the uneven geographical distribution of trained clinicians, and the cost of treatment.

Dr. Ritterband and his colleagues assessed the feasibility and efficacy of a fully automated Internet-based intervention called SHUTi (Sleep Healthy Using the Internet).

SHUTi provides instruction on going to bed only when sleepy, getting out of bed when unable to sleep, and returning only when sleep is imminent. The program advises patients to avoid sleep-incompatible activities in the bedroom such as watching television, to forgo daytime napping, and to arise at the same hour every day. Patients also are instructed to improve their sleep hygiene by avoiding nicotine, caffeine, and alcohol before bedtime. SHUTi also addresses “unhelpful” beliefs and thoughts, such as the notion that people absolutely need 8 hours of sleep every night or excessive concern about the consequences of insomnia.

Participants fill out the Insomnia Severity Index (ISI) online and complete weekly sleep diaries. That information is then used to individually tailor recommendations for the coming week, all of which is computed automatically using algorithms developed specifically for SHUTi.

The intervention uses graphics and animation as well as text, and it includes quizzes, brief games, and vignettes to deliver information, Dr. Ritterband and his colleagues said (Arch. Gen. Psychiatry 2009;66:692-8).

They compared insomnia outcomes between 22 insomnia patients randomly assigned to the SHUTi intervention and 22 control patients who were wait-listed to participate in the program.

The mean age of participants was 45 years; they had had sleep problems for an average of more than 10 years, and at the time of enrollment they reported disruptive sleep more than 5 nights per week.

The intervention group showed marked improvement in insomnia severity at the conclusion of the program as well as 6 months later, while the control group showed little change. Sixteen of the intervention subjects (73%) were judged to be in remission by ISI score, compared with none of the control subjects.

“It is important to highlight that the treatment effect sizes found using this Internet intervention, which was delivered with no human support and at a relatively low cost, are comparable to those found in face-to-face studies,” the investigators said.

They also pointed out that this intervention might expand treatment options for adults whose geographical location prohibits access to care.

However, Dr. Ritterband and his colleagues added that their study sample was “small, relatively homogeneous, well educated, and restricted to individuals with primary insomnia and no comorbidities. Future studies should enroll larger and more heterogeneous samples to improve the generalizability of the findings.”

No relevant conflicts of interest were reported. The study was supported by a grant from the National Institute of Mental Health, National Institutes of Health.

The Sleep Healthy Using the Internet (SHUTi) intervention advises patients to arise at the same hour every day.

Source ©Karen Winton/iStockphoto.com

A cognitive-behavioral therapy intervention delivered via the Internet significantly reduced insomnia severity and contributed to overall sleep improvement in a study of 44 adults, according to a report in the Archives of General Psychiatry.

The 9-week intervention reduced the number of nighttime awakenings and improved sleep efficiency to a similar degree as has been reported for face-to-face CBT, self-help bibliotherapy, group therapy, telephone therapy, and pharmacotherapy, said Lee M. Ritterband, Ph.D., of the University of Virginia Health System, Charlottesville, and his associates.

“An effective and inexpensive Internet intervention would expand treatment options for large numbers of adults with insomnia, especially those whose geographical location prohibits access to relevant care, and could be a substantive first-line treatment choice,” they noted. Although traditional CBT is one of the most effective treatments for insomnia, its availability is “severely limited,” in part because of a lack of trained clinicians, the uneven geographical distribution of trained clinicians, and the cost of treatment.

Dr. Ritterband and his colleagues assessed the feasibility and efficacy of a fully automated Internet-based intervention called SHUTi (Sleep Healthy Using the Internet).

SHUTi provides instruction on going to bed only when sleepy, getting out of bed when unable to sleep, and returning only when sleep is imminent. The program advises patients to avoid sleep-incompatible activities in the bedroom such as watching television, to forgo daytime napping, and to arise at the same hour every day. Patients also are instructed to improve their sleep hygiene by avoiding nicotine, caffeine, and alcohol before bedtime. SHUTi also addresses “unhelpful” beliefs and thoughts, such as the notion that people absolutely need 8 hours of sleep every night or excessive concern about the consequences of insomnia.

Participants fill out the Insomnia Severity Index (ISI) online and complete weekly sleep diaries. That information is then used to individually tailor recommendations for the coming week, all of which is computed automatically using algorithms developed specifically for SHUTi.

The intervention uses graphics and animation as well as text, and it includes quizzes, brief games, and vignettes to deliver information, Dr. Ritterband and his colleagues said (Arch. Gen. Psychiatry 2009;66:692-8).

They compared insomnia outcomes between 22 insomnia patients randomly assigned to the SHUTi intervention and 22 control patients who were wait-listed to participate in the program.

The mean age of participants was 45 years; they had had sleep problems for an average of more than 10 years, and at the time of enrollment they reported disruptive sleep more than 5 nights per week.

The intervention group showed marked improvement in insomnia severity at the conclusion of the program as well as 6 months later, while the control group showed little change. Sixteen of the intervention subjects (73%) were judged to be in remission by ISI score, compared with none of the control subjects.

“It is important to highlight that the treatment effect sizes found using this Internet intervention, which was delivered with no human support and at a relatively low cost, are comparable to those found in face-to-face studies,” the investigators said.

They also pointed out that this intervention might expand treatment options for adults whose geographical location prohibits access to care.

However, Dr. Ritterband and his colleagues added that their study sample was “small, relatively homogeneous, well educated, and restricted to individuals with primary insomnia and no comorbidities. Future studies should enroll larger and more heterogeneous samples to improve the generalizability of the findings.”

No relevant conflicts of interest were reported. The study was supported by a grant from the National Institute of Mental Health, National Institutes of Health.

The Sleep Healthy Using the Internet (SHUTi) intervention advises patients to arise at the same hour every day.

Source ©Karen Winton/iStockphoto.com

In Sweden's general population, the subcategory of functional dyspepsia known as postprandial distress syndrome is associated with anxiety, Dr. Pertti Aro and his colleagues reported in an article appearing in the July issue of Gastroenterology.

In contrast, the other subcategory of functional dyspepsia–epigastric pain syndrome–is not associated with anxiety, wrote Dr. Aro of the Karolinska Institutet, Stockholm, and his associates.

The two distinct syndromes were delineated in the Rome III diagnostic criteria for functional dyspepsia. Postprandial distress syndrome includes one or more symptoms of bothersome postprandial fullness and early satiation, while epigastric pain syndrome includes unexplained epigastric pain and/or burning. Both occur in patients with no evidence of structural disease that could explain the symptoms.

Because little is known about the epidemiology of “these newly defined syndromes,” Dr. Aro and his associates undertook a population-based assessment of risk factors for them. They hypothesized that psychological distress (anxiety and depression) would be a risk factor for one or both subtypes of functional dyspepsia.

The Kalixanda study examined a representative sample drawn from 21,610 adults residing in Kalix and Haparanda, two neighboring communities in northern Sweden. A total of 1,001 people agreed to undergo esophagogastroduodenoscopy, including biopsy and Helicobacter pylori culturing, to rule out organic disease as the cause of their symptoms.

They also completed the extended Abdominal Symptom Questionnaire, the Hospital Anxiety and Depression Scale (HADS), and provided a complete medical history and demographic data.

At endoscopy, 157 subjects (15%) were deemed to have functional dyspepsia. A total of 52 had epigastric pain syndrome, 122 had postprandial distress syndrome, and 17 had both disorders.

Major anxiety (HADS score of 11 or higher) was associated with functional dyspepsia, but depression was not. When functional dyspepsia was broken down into the two subtypes, anxiety was associated with postprandial distress syndrome but not with epigastric pain syndrome.

In addition, another 157 subjects were found to have “uninvestigated” dyspepsia, a category separate from functional dyspepsia. Both minor anxiety (HADS scores of 8-10) and major anxiety, but not depression, were associated with this form of dyspepsia.

“Whether antianxiety agents have any role in management of dyspepsia is unknown but worthy of further testing,” the researchers wrote.

“To our knowledge, this is the first population-based study in a randomly selected adult population to evaluate risk factors for functional dyspepsia using the Rome III definition, with careful exclusion of organic disease by upper endoscopy,” they said.

The question of whether psychological factors cause functional dyspepsia is a controversial one. Some studies have found that psychological illness not only is associated with but also is a predictor of such a diagnosis, and one study reported that treatment with a combination of an anxiolytic and an antidepressant provided short-term improvement in dyspepsia symptoms.

However, other studies have found no such link or have reported that antianxiety medications have no effect on functional dyspepsia.

“Our results are consistent with the hypothesis that functional dyspepsia is causally linked to anxiety but not to depression. … However, it is also conceivable that having upper gastrointestinal symptoms drives increased anxiety.

“Alternatively, another factor such as a common genetic link could explain the coexistence of anxiety and dyspepsia in the population. … The search for common pathways that induce anxiety and dyspepsia now needs greater attention,” Dr. Aro and his colleagues wrote.

This study was supported in part by AstraZeneca Research and Development, Mölndal, Sweden.

In Sweden's general population, the subcategory of functional dyspepsia known as postprandial distress syndrome is associated with anxiety, Dr. Pertti Aro and his colleagues reported in an article appearing in the July issue of Gastroenterology.

In contrast, the other subcategory of functional dyspepsia–epigastric pain syndrome–is not associated with anxiety, wrote Dr. Aro of the Karolinska Institutet, Stockholm, and his associates.

The two distinct syndromes were delineated in the Rome III diagnostic criteria for functional dyspepsia. Postprandial distress syndrome includes one or more symptoms of bothersome postprandial fullness and early satiation, while epigastric pain syndrome includes unexplained epigastric pain and/or burning. Both occur in patients with no evidence of structural disease that could explain the symptoms.

Because little is known about the epidemiology of “these newly defined syndromes,” Dr. Aro and his associates undertook a population-based assessment of risk factors for them. They hypothesized that psychological distress (anxiety and depression) would be a risk factor for one or both subtypes of functional dyspepsia.

The Kalixanda study examined a representative sample drawn from 21,610 adults residing in Kalix and Haparanda, two neighboring communities in northern Sweden. A total of 1,001 people agreed to undergo esophagogastroduodenoscopy, including biopsy and Helicobacter pylori culturing, to rule out organic disease as the cause of their symptoms.

They also completed the extended Abdominal Symptom Questionnaire, the Hospital Anxiety and Depression Scale (HADS), and provided a complete medical history and demographic data.

At endoscopy, 157 subjects (15%) were deemed to have functional dyspepsia. A total of 52 had epigastric pain syndrome, 122 had postprandial distress syndrome, and 17 had both disorders.

Major anxiety (HADS score of 11 or higher) was associated with functional dyspepsia, but depression was not. When functional dyspepsia was broken down into the two subtypes, anxiety was associated with postprandial distress syndrome but not with epigastric pain syndrome.

In addition, another 157 subjects were found to have “uninvestigated” dyspepsia, a category separate from functional dyspepsia. Both minor anxiety (HADS scores of 8-10) and major anxiety, but not depression, were associated with this form of dyspepsia.

“Whether antianxiety agents have any role in management of dyspepsia is unknown but worthy of further testing,” the researchers wrote.

“To our knowledge, this is the first population-based study in a randomly selected adult population to evaluate risk factors for functional dyspepsia using the Rome III definition, with careful exclusion of organic disease by upper endoscopy,” they said.

The question of whether psychological factors cause functional dyspepsia is a controversial one. Some studies have found that psychological illness not only is associated with but also is a predictor of such a diagnosis, and one study reported that treatment with a combination of an anxiolytic and an antidepressant provided short-term improvement in dyspepsia symptoms.

However, other studies have found no such link or have reported that antianxiety medications have no effect on functional dyspepsia.

“Our results are consistent with the hypothesis that functional dyspepsia is causally linked to anxiety but not to depression. … However, it is also conceivable that having upper gastrointestinal symptoms drives increased anxiety.

“Alternatively, another factor such as a common genetic link could explain the coexistence of anxiety and dyspepsia in the population. … The search for common pathways that induce anxiety and dyspepsia now needs greater attention,” Dr. Aro and his colleagues wrote.

This study was supported in part by AstraZeneca Research and Development, Mölndal, Sweden.

In Sweden's general population, the subcategory of functional dyspepsia known as postprandial distress syndrome is associated with anxiety, Dr. Pertti Aro and his colleagues reported in an article appearing in the July issue of Gastroenterology.

In contrast, the other subcategory of functional dyspepsia–epigastric pain syndrome–is not associated with anxiety, wrote Dr. Aro of the Karolinska Institutet, Stockholm, and his associates.

The two distinct syndromes were delineated in the Rome III diagnostic criteria for functional dyspepsia. Postprandial distress syndrome includes one or more symptoms of bothersome postprandial fullness and early satiation, while epigastric pain syndrome includes unexplained epigastric pain and/or burning. Both occur in patients with no evidence of structural disease that could explain the symptoms.

Because little is known about the epidemiology of “these newly defined syndromes,” Dr. Aro and his associates undertook a population-based assessment of risk factors for them. They hypothesized that psychological distress (anxiety and depression) would be a risk factor for one or both subtypes of functional dyspepsia.

The Kalixanda study examined a representative sample drawn from 21,610 adults residing in Kalix and Haparanda, two neighboring communities in northern Sweden. A total of 1,001 people agreed to undergo esophagogastroduodenoscopy, including biopsy and Helicobacter pylori culturing, to rule out organic disease as the cause of their symptoms.

They also completed the extended Abdominal Symptom Questionnaire, the Hospital Anxiety and Depression Scale (HADS), and provided a complete medical history and demographic data.

At endoscopy, 157 subjects (15%) were deemed to have functional dyspepsia. A total of 52 had epigastric pain syndrome, 122 had postprandial distress syndrome, and 17 had both disorders.

Major anxiety (HADS score of 11 or higher) was associated with functional dyspepsia, but depression was not. When functional dyspepsia was broken down into the two subtypes, anxiety was associated with postprandial distress syndrome but not with epigastric pain syndrome.

In addition, another 157 subjects were found to have “uninvestigated” dyspepsia, a category separate from functional dyspepsia. Both minor anxiety (HADS scores of 8-10) and major anxiety, but not depression, were associated with this form of dyspepsia.

“Whether antianxiety agents have any role in management of dyspepsia is unknown but worthy of further testing,” the researchers wrote.

“To our knowledge, this is the first population-based study in a randomly selected adult population to evaluate risk factors for functional dyspepsia using the Rome III definition, with careful exclusion of organic disease by upper endoscopy,” they said.

The question of whether psychological factors cause functional dyspepsia is a controversial one. Some studies have found that psychological illness not only is associated with but also is a predictor of such a diagnosis, and one study reported that treatment with a combination of an anxiolytic and an antidepressant provided short-term improvement in dyspepsia symptoms.

However, other studies have found no such link or have reported that antianxiety medications have no effect on functional dyspepsia.

“Our results are consistent with the hypothesis that functional dyspepsia is causally linked to anxiety but not to depression. … However, it is also conceivable that having upper gastrointestinal symptoms drives increased anxiety.

“Alternatively, another factor such as a common genetic link could explain the coexistence of anxiety and dyspepsia in the population. … The search for common pathways that induce anxiety and dyspepsia now needs greater attention,” Dr. Aro and his colleagues wrote.

This study was supported in part by AstraZeneca Research and Development, Mölndal, Sweden.

Women who undergo thyroid or parathyroid surgery during pregnancy have more operative complications and require longer hospitalizations than do nonpregnant women who have such surgery, as well as relatively high rates of maternal and fetal complications.

These findings, from “the first population-based study to examine predictors of clinical and economic outcomes” in this patient group, suggest that thyroid and parathyroid surgery are not the low-risk procedures in pregnant women that they are in the general population, said Dr. SreyRam Kuy of Yale University, New Haven, Conn., and associates.

The investigators assessed thyroid and parathyroid procedures in pregnancy because the subject had not been well studied before now, even though most disorders that necessitate such surgery occur in women of childbearing age. In addition, recent attention has focused on developing practice guidelines for pregnant women with endocrine disorders, and there was a glaring lack of evidence on this issue in the literature.

Dr. Kuy and colleagues performed a retrospective cross-sectional analysis of hospital discharge data using “the largest all-payer inpatient database in the United States, with records from approximately 8 million hospital stays each year.” They compared outcomes of 201 pregnant women and 31,155 age-matched nonpregnant women who underwent the surgery for benign thyroid disease, malignant thyroid disease, and hyperparathyroidism between 1999 and 2005.

Pregnant patients had significantly higher rates of surgical complications (24%) than did nonpregnant women (10%), including double the rate of endocrine complications (16% vs. 8%). Pregnant women also had significantly longer median hospital stays (2 days vs. 1 day) and inpatient costs ($6,873 vs. $5,963).

In the subset of women who underwent thyroidectomy, those who were pregnant had a higher rate of surgical complications for both benign disease (27% vs. 14%) and malignant disease (21% vs. 8%), the investigators said (Arch. Surg. 2009;144:399-406).

Although these procedures are considered low risk in the general population, women who underwent thyroid or parathyroid surgery while they were pregnant had a relatively high rate of pregnancy complications. The maternal complication rate was 4.5%, and the fetal complication rate was 5.5%.

Pregnant patients of surgeons who performed a high volume of thyroid and parathyroid procedures showed significantly lower rates of both maternal and fetal complications than did those of less-experienced surgeons. In contrast, hospital volume exerted no effect on complication rates.

“It appears to be essential that pregnant patients who require thyroidectomy or parathyroidectomy be directed to high-volume surgeons to optimize their outcomes,” the researchers said.

Given these findings, the risks and benefits of thyroid and parathyroid surgery must be weighed carefully in pregnant women.

“Thyroidectomy is rarely indicated on an urgent basis unless there is significant concern about the well-being of the mother. For example, airway obstruction from large goiters in symptomatic pregnant women with already compromised breathing from uterine expansion, advanced differentiated thyroid cancer, and poorly differentiated cancers could justify proceeding to thyroidectomy prior to delivery,” the researchers advised.

Similarly, parathyroidectomy during pregnancy is indicated to protect the fetus and prevent neonatal hypoparathyroidism and tetany, they said.

This study was supported by the Robert Wood Johnson Foundation and the U.S. Department of Veterans Affairs. The investigators reported that they had no financial conflicts of interest.

Women who undergo thyroid or parathyroid surgery during pregnancy have more operative complications and require longer hospitalizations than do nonpregnant women who have such surgery, as well as relatively high rates of maternal and fetal complications.

These findings, from “the first population-based study to examine predictors of clinical and economic outcomes” in this patient group, suggest that thyroid and parathyroid surgery are not the low-risk procedures in pregnant women that they are in the general population, said Dr. SreyRam Kuy of Yale University, New Haven, Conn., and associates.

The investigators assessed thyroid and parathyroid procedures in pregnancy because the subject had not been well studied before now, even though most disorders that necessitate such surgery occur in women of childbearing age. In addition, recent attention has focused on developing practice guidelines for pregnant women with endocrine disorders, and there was a glaring lack of evidence on this issue in the literature.

Dr. Kuy and colleagues performed a retrospective cross-sectional analysis of hospital discharge data using “the largest all-payer inpatient database in the United States, with records from approximately 8 million hospital stays each year.” They compared outcomes of 201 pregnant women and 31,155 age-matched nonpregnant women who underwent the surgery for benign thyroid disease, malignant thyroid disease, and hyperparathyroidism between 1999 and 2005.

Pregnant patients had significantly higher rates of surgical complications (24%) than did nonpregnant women (10%), including double the rate of endocrine complications (16% vs. 8%). Pregnant women also had significantly longer median hospital stays (2 days vs. 1 day) and inpatient costs ($6,873 vs. $5,963).

In the subset of women who underwent thyroidectomy, those who were pregnant had a higher rate of surgical complications for both benign disease (27% vs. 14%) and malignant disease (21% vs. 8%), the investigators said (Arch. Surg. 2009;144:399-406).

Although these procedures are considered low risk in the general population, women who underwent thyroid or parathyroid surgery while they were pregnant had a relatively high rate of pregnancy complications. The maternal complication rate was 4.5%, and the fetal complication rate was 5.5%.

Pregnant patients of surgeons who performed a high volume of thyroid and parathyroid procedures showed significantly lower rates of both maternal and fetal complications than did those of less-experienced surgeons. In contrast, hospital volume exerted no effect on complication rates.

“It appears to be essential that pregnant patients who require thyroidectomy or parathyroidectomy be directed to high-volume surgeons to optimize their outcomes,” the researchers said.

Given these findings, the risks and benefits of thyroid and parathyroid surgery must be weighed carefully in pregnant women.

“Thyroidectomy is rarely indicated on an urgent basis unless there is significant concern about the well-being of the mother. For example, airway obstruction from large goiters in symptomatic pregnant women with already compromised breathing from uterine expansion, advanced differentiated thyroid cancer, and poorly differentiated cancers could justify proceeding to thyroidectomy prior to delivery,” the researchers advised.

Similarly, parathyroidectomy during pregnancy is indicated to protect the fetus and prevent neonatal hypoparathyroidism and tetany, they said.

This study was supported by the Robert Wood Johnson Foundation and the U.S. Department of Veterans Affairs. The investigators reported that they had no financial conflicts of interest.

Women who undergo thyroid or parathyroid surgery during pregnancy have more operative complications and require longer hospitalizations than do nonpregnant women who have such surgery, as well as relatively high rates of maternal and fetal complications.

These findings, from “the first population-based study to examine predictors of clinical and economic outcomes” in this patient group, suggest that thyroid and parathyroid surgery are not the low-risk procedures in pregnant women that they are in the general population, said Dr. SreyRam Kuy of Yale University, New Haven, Conn., and associates.

The investigators assessed thyroid and parathyroid procedures in pregnancy because the subject had not been well studied before now, even though most disorders that necessitate such surgery occur in women of childbearing age. In addition, recent attention has focused on developing practice guidelines for pregnant women with endocrine disorders, and there was a glaring lack of evidence on this issue in the literature.

Dr. Kuy and colleagues performed a retrospective cross-sectional analysis of hospital discharge data using “the largest all-payer inpatient database in the United States, with records from approximately 8 million hospital stays each year.” They compared outcomes of 201 pregnant women and 31,155 age-matched nonpregnant women who underwent the surgery for benign thyroid disease, malignant thyroid disease, and hyperparathyroidism between 1999 and 2005.

Pregnant patients had significantly higher rates of surgical complications (24%) than did nonpregnant women (10%), including double the rate of endocrine complications (16% vs. 8%). Pregnant women also had significantly longer median hospital stays (2 days vs. 1 day) and inpatient costs ($6,873 vs. $5,963).

In the subset of women who underwent thyroidectomy, those who were pregnant had a higher rate of surgical complications for both benign disease (27% vs. 14%) and malignant disease (21% vs. 8%), the investigators said (Arch. Surg. 2009;144:399-406).

Although these procedures are considered low risk in the general population, women who underwent thyroid or parathyroid surgery while they were pregnant had a relatively high rate of pregnancy complications. The maternal complication rate was 4.5%, and the fetal complication rate was 5.5%.

Pregnant patients of surgeons who performed a high volume of thyroid and parathyroid procedures showed significantly lower rates of both maternal and fetal complications than did those of less-experienced surgeons. In contrast, hospital volume exerted no effect on complication rates.

“It appears to be essential that pregnant patients who require thyroidectomy or parathyroidectomy be directed to high-volume surgeons to optimize their outcomes,” the researchers said.

Given these findings, the risks and benefits of thyroid and parathyroid surgery must be weighed carefully in pregnant women.

“Thyroidectomy is rarely indicated on an urgent basis unless there is significant concern about the well-being of the mother. For example, airway obstruction from large goiters in symptomatic pregnant women with already compromised breathing from uterine expansion, advanced differentiated thyroid cancer, and poorly differentiated cancers could justify proceeding to thyroidectomy prior to delivery,” the researchers advised.

Similarly, parathyroidectomy during pregnancy is indicated to protect the fetus and prevent neonatal hypoparathyroidism and tetany, they said.

This study was supported by the Robert Wood Johnson Foundation and the U.S. Department of Veterans Affairs. The investigators reported that they had no financial conflicts of interest.

Ending an 8-week course of a proton pump inhibitor caused rebound heartburn, acid regurgitation, and dyspepsia in healthy volunteers, Dr. Christina Reimer and her colleagues reported.

Rebound symptoms were clinically significant in the study subjects, causing mild to moderate discomfort for at least 2 weeks after withdrawal of daily PPI therapy—a “remarkable” finding given that 40% of the study subjects had never experienced such symptoms before, wrote Dr. Reimer of the department of medical gastroenterology at Copenhagen University and her associates.

Although ongoing PPI therapyis indicated only in patients who have persistent gastro-esophageal reflux or who are taking NSAIDs, physicians have long reported that it is difficult to reduce or withdraw the drug after a 4-week or 8-week course of empiric treatment for dyspepsia. This has led some to suspect that perhaps physiologic changes induced by the drug itself cause hypersecretion after the PPI is withdrawn.

To investigate the issue, Dr. Reimer and her colleagues performed a double-blind trial in 120 healthy volunteers who had no acid-related symptoms. Sixty subjects were randomly assigned to receive 40 mg of esomeprazole daily for 8 weeks followed by 4 weeks of identical placebo tablets (withdrawal period), and the other 60 subjects were assigned to 12 weeks of placebo.

All were given antacid tablets to be used as rescue medication if they developed acid-related symptoms during the study.

The study subjects completed weekly electronic questionnaires that included the Gastrointestinal Symptom Rating Scale (GSRS). They also were assessed using the 36-item Short Form Health Survey (SF-36) and gave blood samples so that plasma levels of gastrin and chromogranin A could be tracked as indirect measures of gastric acid suppression and enterochromaffin cell mass.

After active treatment was withdrawn but subjects still thought they were taking the drug, “a significant and increasing difference between the PPI and the placebo group” was seen in dyspepsia and reflux symptom scores. A total of 44% of the PPI group reported heartburn, acid regurgitation, or dyspepsia, compared with only 15% of the placebo group.

The proportion of PPI-treated subjects who reported acid-related symptoms was 22% during the second week after withdrawal, 22% during the third week after withdrawal, and 21% during the fourth week after withdrawal. In contrast, the proportions of placebo subjects who reported such symptoms were 7%, 5%, and 2%, respectively.

The differences between the two groups also were significant for each of the individual components of the acid-related GSRS scores. In contrast, GSRS scores for diarrhea and constipation were not significantly different.

In addition, 52% of the active-treatment group reported using rescue antacids after PPI withdrawal. In contrast, only 11% of the placebo group used rescue antacids.

“Our study results reveal for the first time that profound acid inhibition with a PPI for 8 weeks induces acid-related symptoms in a significant proportion of subjects after withdrawal of therapy,” the investigators said.

Moreover, the increased use of rescue antacids after PPI withdrawal “attests to the clinical relevance of the observed symptoms,” they added.

Other researchers have investigated whether tapering the use of PPIs might help long-term users discontinue the drugs. In one clinical trial, “tapering over 3 weeks did not have a significant effect on the proportion that successfully withdrew treatment, compared to instant discontinuation,” they said.

In their study, subjects continued to report acid-related symptoms 4 weeks after withdrawal, and two other studies of PPI withdrawal showed increased acid secretion at least 8 weeks after PPIs were discontinued. Therefore, the duration of rebound acid hypersecretion remains unknown at present and tapering the medication does not appear to help.

“Our results justify the speculation that PPI dependency could be one of the explanations for the rapidly and continuously increasing use of PPIs,” they noted.

AstraZeneca supplied the medication and placebo used in this study.

Ending an 8-week course of a proton pump inhibitor caused rebound heartburn, acid regurgitation, and dyspepsia in healthy volunteers, Dr. Christina Reimer and her colleagues reported.

Rebound symptoms were clinically significant in the study subjects, causing mild to moderate discomfort for at least 2 weeks after withdrawal of daily PPI therapy—a “remarkable” finding given that 40% of the study subjects had never experienced such symptoms before, wrote Dr. Reimer of the department of medical gastroenterology at Copenhagen University and her associates.

Although ongoing PPI therapyis indicated only in patients who have persistent gastro-esophageal reflux or who are taking NSAIDs, physicians have long reported that it is difficult to reduce or withdraw the drug after a 4-week or 8-week course of empiric treatment for dyspepsia. This has led some to suspect that perhaps physiologic changes induced by the drug itself cause hypersecretion after the PPI is withdrawn.

To investigate the issue, Dr. Reimer and her colleagues performed a double-blind trial in 120 healthy volunteers who had no acid-related symptoms. Sixty subjects were randomly assigned to receive 40 mg of esomeprazole daily for 8 weeks followed by 4 weeks of identical placebo tablets (withdrawal period), and the other 60 subjects were assigned to 12 weeks of placebo.

All were given antacid tablets to be used as rescue medication if they developed acid-related symptoms during the study.

The study subjects completed weekly electronic questionnaires that included the Gastrointestinal Symptom Rating Scale (GSRS). They also were assessed using the 36-item Short Form Health Survey (SF-36) and gave blood samples so that plasma levels of gastrin and chromogranin A could be tracked as indirect measures of gastric acid suppression and enterochromaffin cell mass.

After active treatment was withdrawn but subjects still thought they were taking the drug, “a significant and increasing difference between the PPI and the placebo group” was seen in dyspepsia and reflux symptom scores. A total of 44% of the PPI group reported heartburn, acid regurgitation, or dyspepsia, compared with only 15% of the placebo group.

The proportion of PPI-treated subjects who reported acid-related symptoms was 22% during the second week after withdrawal, 22% during the third week after withdrawal, and 21% during the fourth week after withdrawal. In contrast, the proportions of placebo subjects who reported such symptoms were 7%, 5%, and 2%, respectively.

The differences between the two groups also were significant for each of the individual components of the acid-related GSRS scores. In contrast, GSRS scores for diarrhea and constipation were not significantly different.

In addition, 52% of the active-treatment group reported using rescue antacids after PPI withdrawal. In contrast, only 11% of the placebo group used rescue antacids.

“Our study results reveal for the first time that profound acid inhibition with a PPI for 8 weeks induces acid-related symptoms in a significant proportion of subjects after withdrawal of therapy,” the investigators said.

Moreover, the increased use of rescue antacids after PPI withdrawal “attests to the clinical relevance of the observed symptoms,” they added.

Other researchers have investigated whether tapering the use of PPIs might help long-term users discontinue the drugs. In one clinical trial, “tapering over 3 weeks did not have a significant effect on the proportion that successfully withdrew treatment, compared to instant discontinuation,” they said.

In their study, subjects continued to report acid-related symptoms 4 weeks after withdrawal, and two other studies of PPI withdrawal showed increased acid secretion at least 8 weeks after PPIs were discontinued. Therefore, the duration of rebound acid hypersecretion remains unknown at present and tapering the medication does not appear to help.

“Our results justify the speculation that PPI dependency could be one of the explanations for the rapidly and continuously increasing use of PPIs,” they noted.

AstraZeneca supplied the medication and placebo used in this study.

Ending an 8-week course of a proton pump inhibitor caused rebound heartburn, acid regurgitation, and dyspepsia in healthy volunteers, Dr. Christina Reimer and her colleagues reported.

Rebound symptoms were clinically significant in the study subjects, causing mild to moderate discomfort for at least 2 weeks after withdrawal of daily PPI therapy—a “remarkable” finding given that 40% of the study subjects had never experienced such symptoms before, wrote Dr. Reimer of the department of medical gastroenterology at Copenhagen University and her associates.

Although ongoing PPI therapyis indicated only in patients who have persistent gastro-esophageal reflux or who are taking NSAIDs, physicians have long reported that it is difficult to reduce or withdraw the drug after a 4-week or 8-week course of empiric treatment for dyspepsia. This has led some to suspect that perhaps physiologic changes induced by the drug itself cause hypersecretion after the PPI is withdrawn.

To investigate the issue, Dr. Reimer and her colleagues performed a double-blind trial in 120 healthy volunteers who had no acid-related symptoms. Sixty subjects were randomly assigned to receive 40 mg of esomeprazole daily for 8 weeks followed by 4 weeks of identical placebo tablets (withdrawal period), and the other 60 subjects were assigned to 12 weeks of placebo.

All were given antacid tablets to be used as rescue medication if they developed acid-related symptoms during the study.

The study subjects completed weekly electronic questionnaires that included the Gastrointestinal Symptom Rating Scale (GSRS). They also were assessed using the 36-item Short Form Health Survey (SF-36) and gave blood samples so that plasma levels of gastrin and chromogranin A could be tracked as indirect measures of gastric acid suppression and enterochromaffin cell mass.

After active treatment was withdrawn but subjects still thought they were taking the drug, “a significant and increasing difference between the PPI and the placebo group” was seen in dyspepsia and reflux symptom scores. A total of 44% of the PPI group reported heartburn, acid regurgitation, or dyspepsia, compared with only 15% of the placebo group.

The proportion of PPI-treated subjects who reported acid-related symptoms was 22% during the second week after withdrawal, 22% during the third week after withdrawal, and 21% during the fourth week after withdrawal. In contrast, the proportions of placebo subjects who reported such symptoms were 7%, 5%, and 2%, respectively.

The differences between the two groups also were significant for each of the individual components of the acid-related GSRS scores. In contrast, GSRS scores for diarrhea and constipation were not significantly different.

In addition, 52% of the active-treatment group reported using rescue antacids after PPI withdrawal. In contrast, only 11% of the placebo group used rescue antacids.

“Our study results reveal for the first time that profound acid inhibition with a PPI for 8 weeks induces acid-related symptoms in a significant proportion of subjects after withdrawal of therapy,” the investigators said.

Moreover, the increased use of rescue antacids after PPI withdrawal “attests to the clinical relevance of the observed symptoms,” they added.

Other researchers have investigated whether tapering the use of PPIs might help long-term users discontinue the drugs. In one clinical trial, “tapering over 3 weeks did not have a significant effect on the proportion that successfully withdrew treatment, compared to instant discontinuation,” they said.

In their study, subjects continued to report acid-related symptoms 4 weeks after withdrawal, and two other studies of PPI withdrawal showed increased acid secretion at least 8 weeks after PPIs were discontinued. Therefore, the duration of rebound acid hypersecretion remains unknown at present and tapering the medication does not appear to help.

“Our results justify the speculation that PPI dependency could be one of the explanations for the rapidly and continuously increasing use of PPIs,” they noted.

AstraZeneca supplied the medication and placebo used in this study.

The use of metoclopramide to control nausea and vomiting in the first trimester does not increase the risk for congenital malformations, low birth weight, or perinatal death, according to a recent report.

These findings from a large retrospective cohort study “provide reassurance about the safety of metoclopramide,” which has not been convincingly established until now, wrote Ilan Matok of Ben-Gurion University of the Negev, Beer-Sheva, Israel, and associates.

“Despite its extensive use, only a few studies have assessed the safety to the fetus of maternal exposure to metoclopramide during the first trimester, and the relatively small sizes of these studies limited their power,” they noted.

The researchers assessed singleton deliveries between 1998 and 2007 at the largest HMO in Israel, where metoclopramide is the antiemetic drug of choice during pregnancy. Approximately half of the 81,703 infants in the study were born to Jewish parents and half to Bedouin Muslim parents.

A total of 3,458 (4%) of these infants were exposed to metoclopramide during the first trimester. The mean duration of exposure was 1 week.

The rate of major congenital malformations was 5.3% among exposed infants and 4.9% among unexposed infants, a nonsignificant difference.

The rates of minor congenital malformations (3.8% vs. 3.5%) and of multiple malformations (2.5% vs. 2.3%) also were similar between exposed and nonexposed infants. There also were no significant associations between subclasses of congenital malformations and metoclopramide exposure, nor was there any clustering of anomalies among exposed infants.

When the data were analyzed according to subjects' ethnic backgrounds, the drug did not raise risks to infants of either Jewish or Bedouin Muslim parents (N. Engl. J. Med. 2009;360:2528-35).

Metoclopramide also was not associated with an increased risk of preterm birth, low Apgar scores, perinatal death, or low birth weight.

The researchers reported having no relevant conflicts of interest.

The use of metoclopramide to control nausea and vomiting in the first trimester does not increase the risk for congenital malformations, low birth weight, or perinatal death, according to a recent report.

These findings from a large retrospective cohort study “provide reassurance about the safety of metoclopramide,” which has not been convincingly established until now, wrote Ilan Matok of Ben-Gurion University of the Negev, Beer-Sheva, Israel, and associates.

“Despite its extensive use, only a few studies have assessed the safety to the fetus of maternal exposure to metoclopramide during the first trimester, and the relatively small sizes of these studies limited their power,” they noted.

The researchers assessed singleton deliveries between 1998 and 2007 at the largest HMO in Israel, where metoclopramide is the antiemetic drug of choice during pregnancy. Approximately half of the 81,703 infants in the study were born to Jewish parents and half to Bedouin Muslim parents.

A total of 3,458 (4%) of these infants were exposed to metoclopramide during the first trimester. The mean duration of exposure was 1 week.

The rate of major congenital malformations was 5.3% among exposed infants and 4.9% among unexposed infants, a nonsignificant difference.

The rates of minor congenital malformations (3.8% vs. 3.5%) and of multiple malformations (2.5% vs. 2.3%) also were similar between exposed and nonexposed infants. There also were no significant associations between subclasses of congenital malformations and metoclopramide exposure, nor was there any clustering of anomalies among exposed infants.

When the data were analyzed according to subjects' ethnic backgrounds, the drug did not raise risks to infants of either Jewish or Bedouin Muslim parents (N. Engl. J. Med. 2009;360:2528-35).

Metoclopramide also was not associated with an increased risk of preterm birth, low Apgar scores, perinatal death, or low birth weight.

The researchers reported having no relevant conflicts of interest.

The use of metoclopramide to control nausea and vomiting in the first trimester does not increase the risk for congenital malformations, low birth weight, or perinatal death, according to a recent report.

These findings from a large retrospective cohort study “provide reassurance about the safety of metoclopramide,” which has not been convincingly established until now, wrote Ilan Matok of Ben-Gurion University of the Negev, Beer-Sheva, Israel, and associates.

“Despite its extensive use, only a few studies have assessed the safety to the fetus of maternal exposure to metoclopramide during the first trimester, and the relatively small sizes of these studies limited their power,” they noted.

The researchers assessed singleton deliveries between 1998 and 2007 at the largest HMO in Israel, where metoclopramide is the antiemetic drug of choice during pregnancy. Approximately half of the 81,703 infants in the study were born to Jewish parents and half to Bedouin Muslim parents.

A total of 3,458 (4%) of these infants were exposed to metoclopramide during the first trimester. The mean duration of exposure was 1 week.

The rate of major congenital malformations was 5.3% among exposed infants and 4.9% among unexposed infants, a nonsignificant difference.

The rates of minor congenital malformations (3.8% vs. 3.5%) and of multiple malformations (2.5% vs. 2.3%) also were similar between exposed and nonexposed infants. There also were no significant associations between subclasses of congenital malformations and metoclopramide exposure, nor was there any clustering of anomalies among exposed infants.

When the data were analyzed according to subjects' ethnic backgrounds, the drug did not raise risks to infants of either Jewish or Bedouin Muslim parents (N. Engl. J. Med. 2009;360:2528-35).

Metoclopramide also was not associated with an increased risk of preterm birth, low Apgar scores, perinatal death, or low birth weight.

The researchers reported having no relevant conflicts of interest.