Kerri Wachter

WASHINGTON — Even though the sleeping aid zolpidem does cross the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood samples were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetric and neonatal outcomes among women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes among a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of nonzolpidem psychotropic medications.

In additional analyses, the researchers looked at zolpidem use during the third trimester versus use during the first or second (but not third) trimesters, those taking a low (5 mg or less per day) zolpidem daily dose versus those receiving a greater daily dose, and those with extended (10 weeks or greater) zolpidem exposure versus those with shorter exposure.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

There were no statistically significant differences between the two groups in terms of obstetric and neonatal outcomes. However, there was a trend toward preterm delivery and low-birth-weight infants among women on zolpidem during pregnancy. In the zolpidem group, 27% of the women had a preterm delivery and 16% had low-birth-weight infants, compared with 16% and 8%, respectively, for the nonzolpidem group.

“It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and her colleagues at Emory University's Women's Mental Health Program in Atlanta.

Nine women reported taking zolpidem within 24 hours of delivery, but this could be confirmed for only six women. For these women, zolpidem concentrations at delivery were lower than expected for both maternal plasma (range of less than 4 ng/mL to 64 ng/mL) and umbilical plasma (range of less than 4 ng/mL to 15 ng/mL.

“These concentrations are lower than the peak plasma concentrations reported for healthy adults after a single 5- or 10-mg dose,” the researchers noted. “Zolpidem appears to rapidly clear the fetal circulation; however, if delivery occurs less than 11 hours after the last maternal dose, zolpidem may still be present in the neonatal circulation.”

Women who reported longer zolpidem use during pregnancy (10 weeks or longer) did not have a greater rate of complications. There also appeared to be no difference between drug use in a particular trimester versus use throughout the pregnancy in terms of complications.

Ms. Juric stated she had no conflicts of interest to report.

WASHINGTON — Even though the sleeping aid zolpidem does cross the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood samples were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetric and neonatal outcomes among women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes among a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of nonzolpidem psychotropic medications.

In additional analyses, the researchers looked at zolpidem use during the third trimester versus use during the first or second (but not third) trimesters, those taking a low (5 mg or less per day) zolpidem daily dose versus those receiving a greater daily dose, and those with extended (10 weeks or greater) zolpidem exposure versus those with shorter exposure.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

There were no statistically significant differences between the two groups in terms of obstetric and neonatal outcomes. However, there was a trend toward preterm delivery and low-birth-weight infants among women on zolpidem during pregnancy. In the zolpidem group, 27% of the women had a preterm delivery and 16% had low-birth-weight infants, compared with 16% and 8%, respectively, for the nonzolpidem group.

“It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and her colleagues at Emory University's Women's Mental Health Program in Atlanta.

Nine women reported taking zolpidem within 24 hours of delivery, but this could be confirmed for only six women. For these women, zolpidem concentrations at delivery were lower than expected for both maternal plasma (range of less than 4 ng/mL to 64 ng/mL) and umbilical plasma (range of less than 4 ng/mL to 15 ng/mL.

“These concentrations are lower than the peak plasma concentrations reported for healthy adults after a single 5- or 10-mg dose,” the researchers noted. “Zolpidem appears to rapidly clear the fetal circulation; however, if delivery occurs less than 11 hours after the last maternal dose, zolpidem may still be present in the neonatal circulation.”

Women who reported longer zolpidem use during pregnancy (10 weeks or longer) did not have a greater rate of complications. There also appeared to be no difference between drug use in a particular trimester versus use throughout the pregnancy in terms of complications.

Ms. Juric stated she had no conflicts of interest to report.

WASHINGTON — Even though the sleeping aid zolpidem does cross the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood samples were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetric and neonatal outcomes among women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes among a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of nonzolpidem psychotropic medications.

In additional analyses, the researchers looked at zolpidem use during the third trimester versus use during the first or second (but not third) trimesters, those taking a low (5 mg or less per day) zolpidem daily dose versus those receiving a greater daily dose, and those with extended (10 weeks or greater) zolpidem exposure versus those with shorter exposure.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

There were no statistically significant differences between the two groups in terms of obstetric and neonatal outcomes. However, there was a trend toward preterm delivery and low-birth-weight infants among women on zolpidem during pregnancy. In the zolpidem group, 27% of the women had a preterm delivery and 16% had low-birth-weight infants, compared with 16% and 8%, respectively, for the nonzolpidem group.

“It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and her colleagues at Emory University's Women's Mental Health Program in Atlanta.

Nine women reported taking zolpidem within 24 hours of delivery, but this could be confirmed for only six women. For these women, zolpidem concentrations at delivery were lower than expected for both maternal plasma (range of less than 4 ng/mL to 64 ng/mL) and umbilical plasma (range of less than 4 ng/mL to 15 ng/mL.

“These concentrations are lower than the peak plasma concentrations reported for healthy adults after a single 5- or 10-mg dose,” the researchers noted. “Zolpidem appears to rapidly clear the fetal circulation; however, if delivery occurs less than 11 hours after the last maternal dose, zolpidem may still be present in the neonatal circulation.”

Women who reported longer zolpidem use during pregnancy (10 weeks or longer) did not have a greater rate of complications. There also appeared to be no difference between drug use in a particular trimester versus use throughout the pregnancy in terms of complications.

Ms. Juric stated she had no conflicts of interest to report.

WASHINGTON — The key to managing multiple comorbidities is to identify the highest priorities for an individual patient, according to Dr. Cynthia M. Boyd.

Start by considering how the treatment of each condition may complement or hinder others. “What you need to do for one condition may end up affecting or competing with what you might do for another condition,” said Dr. Boyd, of the division of geriatric medicine and gerontology at Johns Hopkins University, Baltimore.

Think of conditions in terms of clinical dominance and concordance or discordance, she said at the annual meeting of the American College of Physicians. This framework is borrowed from diabetes care, but it makes sense for other conditions as well (Diabetes Care 2006;29:725-31).

Clinically dominant conditions are those that are so complex or serious that they eclipse the management of other health problems. Examples include cancer, end-stage renal disease, and severe osteoarthritis.

When there is no clinically dominant condition, think in terms of concordant and discordant conditions. Concordant conditions represent parts of the same overall pathophysiologic risk profile and are more likely to be the focus of a shared management plan. Diabetes, hypertension, and coronary artery disease are examples of concordant conditions, she said.

Discordant conditions are not directly related in either pathogenesis or management and do not share an underlying predisposing factor. The coexistence of chronic obstructive pulmonary disorder and depression, or heart failure and renal failure, are examples of discordant conditions. “More often than not, you might end up struggling a bit in terms of coming up with a management plan to meet the goals of both conditions,” Dr. Boyd said.

Keep in mind that some conditions may heighten the complexity of managing the index condition. For example, renal insufficiency often limits medication choices for other conditions.

Clinical practice guidelines don't offer much help for the management of patients with multiple comorbidities. Guidelines are often developed for a single disease. When other diseases are addressed, it's in the context of how that single disease may alter treatment of the index condition.

There is also limited evidence on the applicability of clinical practice guidelines to older patients with multiple comorbidities, as these are the patients who are typically excluded from clinical trials. In addition, guidelines rarely address quality of life or patient preferences.

Symptomatic versus asymptomatic conditions—as well as what's important to patients—play an important role in quality of life. The management of an asymptomatic condition may be less important to a patient. Talk with patients about what their priorities are. Also talk with caregivers and family members to learn their priorities, which may often focus on maintaining patient independence.

Not only do multiple comorbidities pose a management risk for physicians, but patients also face a treatment burden. Just taking all of the medications according to direction can be difficult. In addition, patients are asked to factor in dietary recommendations, nonpharmacologic therapies, protective strategies and exercises, self-monitoring, and periodic exams and referrals, so one should try to minimize the number of medications and simplify directions and schedules.

Last, remember that management priorities can change over time, Dr. Boyd said, so it's important to periodically reassess them.

WASHINGTON — The key to managing multiple comorbidities is to identify the highest priorities for an individual patient, according to Dr. Cynthia M. Boyd.

Start by considering how the treatment of each condition may complement or hinder others. “What you need to do for one condition may end up affecting or competing with what you might do for another condition,” said Dr. Boyd, of the division of geriatric medicine and gerontology at Johns Hopkins University, Baltimore.

Think of conditions in terms of clinical dominance and concordance or discordance, she said at the annual meeting of the American College of Physicians. This framework is borrowed from diabetes care, but it makes sense for other conditions as well (Diabetes Care 2006;29:725-31).

Clinically dominant conditions are those that are so complex or serious that they eclipse the management of other health problems. Examples include cancer, end-stage renal disease, and severe osteoarthritis.

When there is no clinically dominant condition, think in terms of concordant and discordant conditions. Concordant conditions represent parts of the same overall pathophysiologic risk profile and are more likely to be the focus of a shared management plan. Diabetes, hypertension, and coronary artery disease are examples of concordant conditions, she said.

Discordant conditions are not directly related in either pathogenesis or management and do not share an underlying predisposing factor. The coexistence of chronic obstructive pulmonary disorder and depression, or heart failure and renal failure, are examples of discordant conditions. “More often than not, you might end up struggling a bit in terms of coming up with a management plan to meet the goals of both conditions,” Dr. Boyd said.

Keep in mind that some conditions may heighten the complexity of managing the index condition. For example, renal insufficiency often limits medication choices for other conditions.

Clinical practice guidelines don't offer much help for the management of patients with multiple comorbidities. Guidelines are often developed for a single disease. When other diseases are addressed, it's in the context of how that single disease may alter treatment of the index condition.

There is also limited evidence on the applicability of clinical practice guidelines to older patients with multiple comorbidities, as these are the patients who are typically excluded from clinical trials. In addition, guidelines rarely address quality of life or patient preferences.

Symptomatic versus asymptomatic conditions—as well as what's important to patients—play an important role in quality of life. The management of an asymptomatic condition may be less important to a patient. Talk with patients about what their priorities are. Also talk with caregivers and family members to learn their priorities, which may often focus on maintaining patient independence.

Not only do multiple comorbidities pose a management risk for physicians, but patients also face a treatment burden. Just taking all of the medications according to direction can be difficult. In addition, patients are asked to factor in dietary recommendations, nonpharmacologic therapies, protective strategies and exercises, self-monitoring, and periodic exams and referrals, so one should try to minimize the number of medications and simplify directions and schedules.

Last, remember that management priorities can change over time, Dr. Boyd said, so it's important to periodically reassess them.

WASHINGTON — The key to managing multiple comorbidities is to identify the highest priorities for an individual patient, according to Dr. Cynthia M. Boyd.

Start by considering how the treatment of each condition may complement or hinder others. “What you need to do for one condition may end up affecting or competing with what you might do for another condition,” said Dr. Boyd, of the division of geriatric medicine and gerontology at Johns Hopkins University, Baltimore.

Think of conditions in terms of clinical dominance and concordance or discordance, she said at the annual meeting of the American College of Physicians. This framework is borrowed from diabetes care, but it makes sense for other conditions as well (Diabetes Care 2006;29:725-31).

Clinically dominant conditions are those that are so complex or serious that they eclipse the management of other health problems. Examples include cancer, end-stage renal disease, and severe osteoarthritis.

When there is no clinically dominant condition, think in terms of concordant and discordant conditions. Concordant conditions represent parts of the same overall pathophysiologic risk profile and are more likely to be the focus of a shared management plan. Diabetes, hypertension, and coronary artery disease are examples of concordant conditions, she said.

Discordant conditions are not directly related in either pathogenesis or management and do not share an underlying predisposing factor. The coexistence of chronic obstructive pulmonary disorder and depression, or heart failure and renal failure, are examples of discordant conditions. “More often than not, you might end up struggling a bit in terms of coming up with a management plan to meet the goals of both conditions,” Dr. Boyd said.

Keep in mind that some conditions may heighten the complexity of managing the index condition. For example, renal insufficiency often limits medication choices for other conditions.

Clinical practice guidelines don't offer much help for the management of patients with multiple comorbidities. Guidelines are often developed for a single disease. When other diseases are addressed, it's in the context of how that single disease may alter treatment of the index condition.

There is also limited evidence on the applicability of clinical practice guidelines to older patients with multiple comorbidities, as these are the patients who are typically excluded from clinical trials. In addition, guidelines rarely address quality of life or patient preferences.

Symptomatic versus asymptomatic conditions—as well as what's important to patients—play an important role in quality of life. The management of an asymptomatic condition may be less important to a patient. Talk with patients about what their priorities are. Also talk with caregivers and family members to learn their priorities, which may often focus on maintaining patient independence.

Not only do multiple comorbidities pose a management risk for physicians, but patients also face a treatment burden. Just taking all of the medications according to direction can be difficult. In addition, patients are asked to factor in dietary recommendations, nonpharmacologic therapies, protective strategies and exercises, self-monitoring, and periodic exams and referrals, so one should try to minimize the number of medications and simplify directions and schedules.

Last, remember that management priorities can change over time, Dr. Boyd said, so it's important to periodically reassess them.

CHICAGO — Gabapentin and four newer antidepressants significantly reduce hot flash activity, according to a meta-analysis of 10 placebo-controlled studies that was presented as a poster at the annual meeting of the American Society of Clinical Oncology.

As a group, the antidepressants—paroxetine (Paxil), venlafaxine (Effexor), fluoxetine (Prozac), and sertraline (Zoloft)—decreased absolute hot flash scores 26% more than was seen with their corresponding placebo arms (P = .0001), reported Dr. Charles L. Loprinzi, professor of oncology at the Mayo Clinic, Rochester, Minn., and his coauthors.

Three trials showed that gabapentin (Neurontin) decreased absolute hot flashes 35%–38% more than did their corresponding placebo arms (P = .0001).

“This current pooled analysis does support that both newer antidepressants and gabapentin are useful for relieving hot flashes in women. It suggests, however, that the efficacy of newer antidepressants is not identical between the agents,” the investigators wrote.

Among the antidepressants, they reported paroxetine and venlafaxine appear to decrease hot flashes more than do sertraline or fluoxetine.

The antidepressants—with the exception of venlafaxine—are selective serotonin reuptake inhibitors that are primarily indicated for treatment of major depressive disorder, obsessive compulsive disorder, and panic disorder.

Paroxetine and sertraline are also indicated for the treatment of social anxiety disorder and posttraumatic stress disorder. Venlafaxine is a mixed serotonin and norepinephrine inhibitor that is indicated for the treatment of major depressive disorder.

Several researchers, including Dr. Loprinzi, have speculated that serotonin modulation plays a role in the effectiveness of these antidepressants against hot flashes.

Gabapentin is indicated for the treatment of postherpetic neuralgia and as an adjunctive treatment of partial seizures in patients with epilepsy. The drug inhibits neuronal calcium currents in vitro, which is hypothesized to play a role in the effectiveness of the drug against neuropathic pain.

Dr. Loprinzi and others have speculated that “similar upregulation of the gabapentin binding site could be involved in the hypothalamus as a result of oestrogen withdrawal, leading to increased activity of the neurotransmitters in the hypothalamus. Gabapentin might exert its effect on hot flashes by this mechanism” (Lancet 2005;366:818-24).

For the analysis, the researchers collected individual patient data (for 10 previous studies assessing the efficacy of paroxetine (2 studies), venlafaxine (1 study), fluoxetine (1 study), sertraline (3 studies), and gabapentin (3 studies).

The change in hot flash activity from baseline to week 4 for each agent was calculated using both weighted and unweighted approaches. The size of the study was used for weighting. Regression models and linear random effects were used to adjust for the effects of age, breast cancer history, and tamoxifen use on hot flash activity.

Data from 1,341 patients indicated that paroxetine, venlafaxine, fluoxetine, and sertraline decreased absolute hot flash scores, respectively, 41%, 33%, 13%, and 3%–18% more than did their corresponding placebo arms. Results were similar for the weighted and unweighted effect size approaches. Adjustment for age, breast cancer history, and tamoxifen use did not have an impact on the findings.

Dr. Loprinzi reported that he has served as a consultant to Concert Pharmaceuticals Inc. Several of his coauthors reported financial relationships with other pharmaceutical companies, including Wyeth, JDS Pharmaceuticals (now owned by Noven Pharmaceuticals Inc.), Depomed Inc., and GlaxoSmithKline.

The newer anti-depressesantsall relieve hot flashes, but the efficacy is not identical among them. DR. LOPRINZI

CHICAGO — Gabapentin and four newer antidepressants significantly reduce hot flash activity, according to a meta-analysis of 10 placebo-controlled studies that was presented as a poster at the annual meeting of the American Society of Clinical Oncology.

As a group, the antidepressants—paroxetine (Paxil), venlafaxine (Effexor), fluoxetine (Prozac), and sertraline (Zoloft)—decreased absolute hot flash scores 26% more than was seen with their corresponding placebo arms (P = .0001), reported Dr. Charles L. Loprinzi, professor of oncology at the Mayo Clinic, Rochester, Minn., and his coauthors.

Three trials showed that gabapentin (Neurontin) decreased absolute hot flashes 35%–38% more than did their corresponding placebo arms (P = .0001).

“This current pooled analysis does support that both newer antidepressants and gabapentin are useful for relieving hot flashes in women. It suggests, however, that the efficacy of newer antidepressants is not identical between the agents,” the investigators wrote.

Among the antidepressants, they reported paroxetine and venlafaxine appear to decrease hot flashes more than do sertraline or fluoxetine.

The antidepressants—with the exception of venlafaxine—are selective serotonin reuptake inhibitors that are primarily indicated for treatment of major depressive disorder, obsessive compulsive disorder, and panic disorder.

Paroxetine and sertraline are also indicated for the treatment of social anxiety disorder and posttraumatic stress disorder. Venlafaxine is a mixed serotonin and norepinephrine inhibitor that is indicated for the treatment of major depressive disorder.

Several researchers, including Dr. Loprinzi, have speculated that serotonin modulation plays a role in the effectiveness of these antidepressants against hot flashes.

Gabapentin is indicated for the treatment of postherpetic neuralgia and as an adjunctive treatment of partial seizures in patients with epilepsy. The drug inhibits neuronal calcium currents in vitro, which is hypothesized to play a role in the effectiveness of the drug against neuropathic pain.

Dr. Loprinzi and others have speculated that “similar upregulation of the gabapentin binding site could be involved in the hypothalamus as a result of oestrogen withdrawal, leading to increased activity of the neurotransmitters in the hypothalamus. Gabapentin might exert its effect on hot flashes by this mechanism” (Lancet 2005;366:818-24).

For the analysis, the researchers collected individual patient data (for 10 previous studies assessing the efficacy of paroxetine (2 studies), venlafaxine (1 study), fluoxetine (1 study), sertraline (3 studies), and gabapentin (3 studies).

The change in hot flash activity from baseline to week 4 for each agent was calculated using both weighted and unweighted approaches. The size of the study was used for weighting. Regression models and linear random effects were used to adjust for the effects of age, breast cancer history, and tamoxifen use on hot flash activity.

Data from 1,341 patients indicated that paroxetine, venlafaxine, fluoxetine, and sertraline decreased absolute hot flash scores, respectively, 41%, 33%, 13%, and 3%–18% more than did their corresponding placebo arms. Results were similar for the weighted and unweighted effect size approaches. Adjustment for age, breast cancer history, and tamoxifen use did not have an impact on the findings.

Dr. Loprinzi reported that he has served as a consultant to Concert Pharmaceuticals Inc. Several of his coauthors reported financial relationships with other pharmaceutical companies, including Wyeth, JDS Pharmaceuticals (now owned by Noven Pharmaceuticals Inc.), Depomed Inc., and GlaxoSmithKline.

The newer anti-depressesantsall relieve hot flashes, but the efficacy is not identical among them. DR. LOPRINZI

CHICAGO — Gabapentin and four newer antidepressants significantly reduce hot flash activity, according to a meta-analysis of 10 placebo-controlled studies that was presented as a poster at the annual meeting of the American Society of Clinical Oncology.

As a group, the antidepressants—paroxetine (Paxil), venlafaxine (Effexor), fluoxetine (Prozac), and sertraline (Zoloft)—decreased absolute hot flash scores 26% more than was seen with their corresponding placebo arms (P = .0001), reported Dr. Charles L. Loprinzi, professor of oncology at the Mayo Clinic, Rochester, Minn., and his coauthors.

Three trials showed that gabapentin (Neurontin) decreased absolute hot flashes 35%–38% more than did their corresponding placebo arms (P = .0001).

“This current pooled analysis does support that both newer antidepressants and gabapentin are useful for relieving hot flashes in women. It suggests, however, that the efficacy of newer antidepressants is not identical between the agents,” the investigators wrote.

Among the antidepressants, they reported paroxetine and venlafaxine appear to decrease hot flashes more than do sertraline or fluoxetine.

The antidepressants—with the exception of venlafaxine—are selective serotonin reuptake inhibitors that are primarily indicated for treatment of major depressive disorder, obsessive compulsive disorder, and panic disorder.

Paroxetine and sertraline are also indicated for the treatment of social anxiety disorder and posttraumatic stress disorder. Venlafaxine is a mixed serotonin and norepinephrine inhibitor that is indicated for the treatment of major depressive disorder.

Several researchers, including Dr. Loprinzi, have speculated that serotonin modulation plays a role in the effectiveness of these antidepressants against hot flashes.

Gabapentin is indicated for the treatment of postherpetic neuralgia and as an adjunctive treatment of partial seizures in patients with epilepsy. The drug inhibits neuronal calcium currents in vitro, which is hypothesized to play a role in the effectiveness of the drug against neuropathic pain.

Dr. Loprinzi and others have speculated that “similar upregulation of the gabapentin binding site could be involved in the hypothalamus as a result of oestrogen withdrawal, leading to increased activity of the neurotransmitters in the hypothalamus. Gabapentin might exert its effect on hot flashes by this mechanism” (Lancet 2005;366:818-24).

For the analysis, the researchers collected individual patient data (for 10 previous studies assessing the efficacy of paroxetine (2 studies), venlafaxine (1 study), fluoxetine (1 study), sertraline (3 studies), and gabapentin (3 studies).

The change in hot flash activity from baseline to week 4 for each agent was calculated using both weighted and unweighted approaches. The size of the study was used for weighting. Regression models and linear random effects were used to adjust for the effects of age, breast cancer history, and tamoxifen use on hot flash activity.

Data from 1,341 patients indicated that paroxetine, venlafaxine, fluoxetine, and sertraline decreased absolute hot flash scores, respectively, 41%, 33%, 13%, and 3%–18% more than did their corresponding placebo arms. Results were similar for the weighted and unweighted effect size approaches. Adjustment for age, breast cancer history, and tamoxifen use did not have an impact on the findings.

Dr. Loprinzi reported that he has served as a consultant to Concert Pharmaceuticals Inc. Several of his coauthors reported financial relationships with other pharmaceutical companies, including Wyeth, JDS Pharmaceuticals (now owned by Noven Pharmaceuticals Inc.), Depomed Inc., and GlaxoSmithKline.

The newer anti-depressesantsall relieve hot flashes, but the efficacy is not identical among them. DR. LOPRINZI

WASHINGTON — The key to managing multiple comorbidities is to identify the highest priorities for an individual patient, according to Dr. Cynthia M. Boyd.

Start by considering how the treatment of each condition may complement or hinder others. “What you need to do for one condition may end up affecting or competing with what you might do for another condition,” said Dr. Boyd of the division of geriatric medicine and gerontology at Johns Hopkins University, Baltimore.

Think of conditions in terms of clinical dominance and concordance or discordance, she advised at the annual meeting of the American College of Physicians. This framework, borrowed from diabetes care, makes sense for other conditions as well (Diabetes Care 2006;29:725–31).

Clinically dominant conditions are those that are so complex or serious that they eclipse other health problems. Examples include cancer, end-stage renal disease, and severe osteoarthritis.

When there is no clinically dominant condition, think in terms of concordant and discordant conditions. Concordant conditions represent parts of an overall pathophysiologic risk profile and are more likely to be the focus of a shared management plan. Diabetes, hypertension, and coronary artery disease are examples.

Discordant conditions are not directly related in either pathogenesis or management. The coexistence of chronic obstructive pulmonary disorder and depression, or heart failure and renal failure, are examples. “More often than not, you might end up struggling a bit in terms of coming up with a management plan to meet the goals of both conditions,” Dr. Boyd said.

Clinical practice guidelines are often developed for a single disease. When other diseases are addressed, it's in the context of how that single disease may alter treatment of the index condition. There is limited evidence on the applicability of clinical practice guidelines to older patients with multiple comorbidities, as such patients are typically excluded from clinical trials.

Symptomatic vs. asymptomatic conditions—and what's important to patients—play an important role in quality of life. The management of an asymptomatic condition may be less important to a patient. Talk with patients about what their priorities are. Also talk with caregivers and family members to learn their priorities.

Not only do multiple comorbidities pose a management risk for physicians, patients face a treatment burden. Just taking all medications according to direction can be difficult. In addition, patients are asked to factor in dietary recommendations, nonpharmacologic therapies, self-monitoring, protective strategies and exercises, and periodic exams and referrals. Try to minimize the number of medications and simplify directions and schedules.

Last, remember that management priorities can change over time, so it's important to periodically reassess them.

WASHINGTON — The key to managing multiple comorbidities is to identify the highest priorities for an individual patient, according to Dr. Cynthia M. Boyd.

Start by considering how the treatment of each condition may complement or hinder others. “What you need to do for one condition may end up affecting or competing with what you might do for another condition,” said Dr. Boyd of the division of geriatric medicine and gerontology at Johns Hopkins University, Baltimore.

Think of conditions in terms of clinical dominance and concordance or discordance, she advised at the annual meeting of the American College of Physicians. This framework, borrowed from diabetes care, makes sense for other conditions as well (Diabetes Care 2006;29:725–31).

Clinically dominant conditions are those that are so complex or serious that they eclipse other health problems. Examples include cancer, end-stage renal disease, and severe osteoarthritis.

When there is no clinically dominant condition, think in terms of concordant and discordant conditions. Concordant conditions represent parts of an overall pathophysiologic risk profile and are more likely to be the focus of a shared management plan. Diabetes, hypertension, and coronary artery disease are examples.

Discordant conditions are not directly related in either pathogenesis or management. The coexistence of chronic obstructive pulmonary disorder and depression, or heart failure and renal failure, are examples. “More often than not, you might end up struggling a bit in terms of coming up with a management plan to meet the goals of both conditions,” Dr. Boyd said.

Clinical practice guidelines are often developed for a single disease. When other diseases are addressed, it's in the context of how that single disease may alter treatment of the index condition. There is limited evidence on the applicability of clinical practice guidelines to older patients with multiple comorbidities, as such patients are typically excluded from clinical trials.

Symptomatic vs. asymptomatic conditions—and what's important to patients—play an important role in quality of life. The management of an asymptomatic condition may be less important to a patient. Talk with patients about what their priorities are. Also talk with caregivers and family members to learn their priorities.

Not only do multiple comorbidities pose a management risk for physicians, patients face a treatment burden. Just taking all medications according to direction can be difficult. In addition, patients are asked to factor in dietary recommendations, nonpharmacologic therapies, self-monitoring, protective strategies and exercises, and periodic exams and referrals. Try to minimize the number of medications and simplify directions and schedules.

Last, remember that management priorities can change over time, so it's important to periodically reassess them.

WASHINGTON — The key to managing multiple comorbidities is to identify the highest priorities for an individual patient, according to Dr. Cynthia M. Boyd.

Start by considering how the treatment of each condition may complement or hinder others. “What you need to do for one condition may end up affecting or competing with what you might do for another condition,” said Dr. Boyd of the division of geriatric medicine and gerontology at Johns Hopkins University, Baltimore.

Think of conditions in terms of clinical dominance and concordance or discordance, she advised at the annual meeting of the American College of Physicians. This framework, borrowed from diabetes care, makes sense for other conditions as well (Diabetes Care 2006;29:725–31).

Clinically dominant conditions are those that are so complex or serious that they eclipse other health problems. Examples include cancer, end-stage renal disease, and severe osteoarthritis.

When there is no clinically dominant condition, think in terms of concordant and discordant conditions. Concordant conditions represent parts of an overall pathophysiologic risk profile and are more likely to be the focus of a shared management plan. Diabetes, hypertension, and coronary artery disease are examples.

Discordant conditions are not directly related in either pathogenesis or management. The coexistence of chronic obstructive pulmonary disorder and depression, or heart failure and renal failure, are examples. “More often than not, you might end up struggling a bit in terms of coming up with a management plan to meet the goals of both conditions,” Dr. Boyd said.

Clinical practice guidelines are often developed for a single disease. When other diseases are addressed, it's in the context of how that single disease may alter treatment of the index condition. There is limited evidence on the applicability of clinical practice guidelines to older patients with multiple comorbidities, as such patients are typically excluded from clinical trials.

Symptomatic vs. asymptomatic conditions—and what's important to patients—play an important role in quality of life. The management of an asymptomatic condition may be less important to a patient. Talk with patients about what their priorities are. Also talk with caregivers and family members to learn their priorities.

Not only do multiple comorbidities pose a management risk for physicians, patients face a treatment burden. Just taking all medications according to direction can be difficult. In addition, patients are asked to factor in dietary recommendations, nonpharmacologic therapies, self-monitoring, protective strategies and exercises, and periodic exams and referrals. Try to minimize the number of medications and simplify directions and schedules.

Last, remember that management priorities can change over time, so it's important to periodically reassess them.

The PET tracer Pittsburgh Compound B is labeled with C11, which has a half-life of only 20 minutes.

That means that researchers who wish to use the tracer to study Alzheimer's disease (AD) must have either an on-site cyclotron to generate the isotope, or have access to a cyclotron very nearby, said Dr. Dean F. Wong, a professor of radiology, psychiatry, neuroscience, and environmental health sciences at Johns Hopkins University, Baltimore. This need for a nearby cyclotron cuts down on the number of researchers who can use the tracer to investigate the role of amyloid in Alzheimer's.

Given this limitation, the search is on to find a more time-friendly radiotracer that also binds to amyloid plaques.

Several F18-labeled compounds are currently under investigation.

F18 compounds are especially attractive because the radioisotope has a half-life of 110 minutes.

Like Pittsburgh Compound B, which is derived from thioflavine—a dye that is currently used in autopsy tissue studies to highlight amyloid fibrils in the brain—F18-based tracers are based on stilbene dyes.

Dr. Wong and his colleagues presented data, obtained in part from research done at Johns Hopkins University, on one such tracer, AV-45—currently under development by Avid Radiopharmaceuticals Inc.—at the recent 2008 Society of Nuclear Medicine annual meeting.

Using AV-45, they were able to correctly identify individuals with possible or probable AD based on clinical criteria.

In addition, the investigators were able to use the technique to identify amyloid plaques in the brains of two healthy control participants.

The technique measures distribution volumes, which represent the amount of tracer collected in a brain area.

This is assumed to be proportional to the amount of amyloid load.

The researchers used mathematical models to better assess how much amyloid is actually binding to brain tissue as opposed to how much is simply collecting in the area.

Validation with postmortem tissue is still needed.

Once validated, the technique would be used to improve the models used to quantify amyloid binding.

The AV-45 compound is currently in phase II trials.

In addition, several companies are interested in using amyloid tracers as biomarkers in drug trials, reported Dr. Wong.

“What I'm excited about is its drug development potential because it might be [usable] as a biomarker for testing new drugs,” he commented.

Once AV-45 is approved, “I can see increasing use of it to test a number of Alzheimer's drugs.”

F18 tracers, like AV-45, could be produced in regional cyclotrons, bringing amyloid imaging to an even larger pool of researchers and even clinicians.

Dr. Wong reported receiving grant support for this study from the National Institutes of Health (NIH) as well as from several pharmaceutical companies.

PET imaging with F-18 AV-45 reveals greater amyloid deposition in the brain of an AD patient (top images). Less amyloid is seen in the healthy control (bottom images). The color gradient from blue to red indicates increasing amyloid. Laboratory of Dr. Dean Wong/Avid Radiopharmaceuticals Inc.

The PET tracer Pittsburgh Compound B is labeled with C11, which has a half-life of only 20 minutes.

That means that researchers who wish to use the tracer to study Alzheimer's disease (AD) must have either an on-site cyclotron to generate the isotope, or have access to a cyclotron very nearby, said Dr. Dean F. Wong, a professor of radiology, psychiatry, neuroscience, and environmental health sciences at Johns Hopkins University, Baltimore. This need for a nearby cyclotron cuts down on the number of researchers who can use the tracer to investigate the role of amyloid in Alzheimer's.

Given this limitation, the search is on to find a more time-friendly radiotracer that also binds to amyloid plaques.

Several F18-labeled compounds are currently under investigation.

F18 compounds are especially attractive because the radioisotope has a half-life of 110 minutes.

Like Pittsburgh Compound B, which is derived from thioflavine—a dye that is currently used in autopsy tissue studies to highlight amyloid fibrils in the brain—F18-based tracers are based on stilbene dyes.

Dr. Wong and his colleagues presented data, obtained in part from research done at Johns Hopkins University, on one such tracer, AV-45—currently under development by Avid Radiopharmaceuticals Inc.—at the recent 2008 Society of Nuclear Medicine annual meeting.

Using AV-45, they were able to correctly identify individuals with possible or probable AD based on clinical criteria.

In addition, the investigators were able to use the technique to identify amyloid plaques in the brains of two healthy control participants.

The technique measures distribution volumes, which represent the amount of tracer collected in a brain area.

This is assumed to be proportional to the amount of amyloid load.

The researchers used mathematical models to better assess how much amyloid is actually binding to brain tissue as opposed to how much is simply collecting in the area.

Validation with postmortem tissue is still needed.

Once validated, the technique would be used to improve the models used to quantify amyloid binding.

The AV-45 compound is currently in phase II trials.

In addition, several companies are interested in using amyloid tracers as biomarkers in drug trials, reported Dr. Wong.

“What I'm excited about is its drug development potential because it might be [usable] as a biomarker for testing new drugs,” he commented.

Once AV-45 is approved, “I can see increasing use of it to test a number of Alzheimer's drugs.”

F18 tracers, like AV-45, could be produced in regional cyclotrons, bringing amyloid imaging to an even larger pool of researchers and even clinicians.

Dr. Wong reported receiving grant support for this study from the National Institutes of Health (NIH) as well as from several pharmaceutical companies.

PET imaging with F-18 AV-45 reveals greater amyloid deposition in the brain of an AD patient (top images). Less amyloid is seen in the healthy control (bottom images). The color gradient from blue to red indicates increasing amyloid. Laboratory of Dr. Dean Wong/Avid Radiopharmaceuticals Inc.

The PET tracer Pittsburgh Compound B is labeled with C11, which has a half-life of only 20 minutes.

That means that researchers who wish to use the tracer to study Alzheimer's disease (AD) must have either an on-site cyclotron to generate the isotope, or have access to a cyclotron very nearby, said Dr. Dean F. Wong, a professor of radiology, psychiatry, neuroscience, and environmental health sciences at Johns Hopkins University, Baltimore. This need for a nearby cyclotron cuts down on the number of researchers who can use the tracer to investigate the role of amyloid in Alzheimer's.

Given this limitation, the search is on to find a more time-friendly radiotracer that also binds to amyloid plaques.

Several F18-labeled compounds are currently under investigation.

F18 compounds are especially attractive because the radioisotope has a half-life of 110 minutes.

Like Pittsburgh Compound B, which is derived from thioflavine—a dye that is currently used in autopsy tissue studies to highlight amyloid fibrils in the brain—F18-based tracers are based on stilbene dyes.

Dr. Wong and his colleagues presented data, obtained in part from research done at Johns Hopkins University, on one such tracer, AV-45—currently under development by Avid Radiopharmaceuticals Inc.—at the recent 2008 Society of Nuclear Medicine annual meeting.

Using AV-45, they were able to correctly identify individuals with possible or probable AD based on clinical criteria.

In addition, the investigators were able to use the technique to identify amyloid plaques in the brains of two healthy control participants.

The technique measures distribution volumes, which represent the amount of tracer collected in a brain area.

This is assumed to be proportional to the amount of amyloid load.

The researchers used mathematical models to better assess how much amyloid is actually binding to brain tissue as opposed to how much is simply collecting in the area.

Validation with postmortem tissue is still needed.

Once validated, the technique would be used to improve the models used to quantify amyloid binding.

The AV-45 compound is currently in phase II trials.

In addition, several companies are interested in using amyloid tracers as biomarkers in drug trials, reported Dr. Wong.

“What I'm excited about is its drug development potential because it might be [usable] as a biomarker for testing new drugs,” he commented.

Once AV-45 is approved, “I can see increasing use of it to test a number of Alzheimer's drugs.”

F18 tracers, like AV-45, could be produced in regional cyclotrons, bringing amyloid imaging to an even larger pool of researchers and even clinicians.

Dr. Wong reported receiving grant support for this study from the National Institutes of Health (NIH) as well as from several pharmaceutical companies.

PET imaging with F-18 AV-45 reveals greater amyloid deposition in the brain of an AD patient (top images). Less amyloid is seen in the healthy control (bottom images). The color gradient from blue to red indicates increasing amyloid. Laboratory of Dr. Dean Wong/Avid Radiopharmaceuticals Inc.

WASHINGTON — Even though the sleeping aid zolpidem crosses the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetrical and neonatal outcomes in women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes in a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of nonzolpidem psychotropic medications.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

There were no statistically significant differences between the two groups in terms of obstetrical and neonatal outcomes. However, there was a trend toward preterm delivery and low-birth-weight infants in women on zolpidem during pregnancy. In that group, 27% of the women had a preterm delivery and 16% had low-birth-weight infants, compared with 16% and 8%, respectively, for the nonzolpidem group.

“It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and colleagues at Emory University's Women's Mental Health Program, Atlanta.

Women who reported longer zolpidem use during pregnancy (10 weeks or longer) did not have a greater rate of complications. There also appeared to be no difference between drug use in a particular trimester versus use throughout the pregnancy in terms of complications. Ms. Juric reported no conflicts of interest.

WASHINGTON — Even though the sleeping aid zolpidem crosses the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetrical and neonatal outcomes in women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes in a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of nonzolpidem psychotropic medications.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

There were no statistically significant differences between the two groups in terms of obstetrical and neonatal outcomes. However, there was a trend toward preterm delivery and low-birth-weight infants in women on zolpidem during pregnancy. In that group, 27% of the women had a preterm delivery and 16% had low-birth-weight infants, compared with 16% and 8%, respectively, for the nonzolpidem group.

“It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and colleagues at Emory University's Women's Mental Health Program, Atlanta.

Women who reported longer zolpidem use during pregnancy (10 weeks or longer) did not have a greater rate of complications. There also appeared to be no difference between drug use in a particular trimester versus use throughout the pregnancy in terms of complications. Ms. Juric reported no conflicts of interest.

WASHINGTON — Even though the sleeping aid zolpidem crosses the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetrical and neonatal outcomes in women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes in a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of nonzolpidem psychotropic medications.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

There were no statistically significant differences between the two groups in terms of obstetrical and neonatal outcomes. However, there was a trend toward preterm delivery and low-birth-weight infants in women on zolpidem during pregnancy. In that group, 27% of the women had a preterm delivery and 16% had low-birth-weight infants, compared with 16% and 8%, respectively, for the nonzolpidem group.

“It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and colleagues at Emory University's Women's Mental Health Program, Atlanta.

Women who reported longer zolpidem use during pregnancy (10 weeks or longer) did not have a greater rate of complications. There also appeared to be no difference between drug use in a particular trimester versus use throughout the pregnancy in terms of complications. Ms. Juric reported no conflicts of interest.

CHICAGO – Citalopram may be an effective option for reducing hot flashes, having performed twice as well as placebo in a randomized, placebo-controlled phase III trial conducted by the North Central Cancer Treatment Group.

“Hot flash relief can be obtained with as little as 10 mg/day citalopram,” Debra Barton, Ph.D., of the Mayo Clinic in Rochester, Minn., and her coauthors concluded in a poster reporting results of the trial at the annual meeting of the American Society of Clinical Oncology.

A selective serotonin reuptake inhibitor (SSRI), citalopram (Celexa) is approved for depression, but is also used for some other disorders.

Postmenopausal women who had a history of breast cancer or wanted to avoid hormones due to breast cancer risk were enrolled in the study. They had to have at least 14 hot flashes per week for at least 1 month. Endocrine therapy was allowed, if the woman was on a stable dose for at least 1 month. No other antidepressants or hot flash therapies were permitted.

All 254 participants kept a record of their hot flashes for 1 week before starting treatment, The investigators randomized the women into four groups that received either (group 1) 10 mg/day of citalopram on weeks 2–7, (group 2) 10 mg/day of citalopram during week 2 followed by 20 mg/day of citalopram for weeks 3–7, (group 3) 10 mg/day of citalopram during week 2 followed by 20 mg/day for week 3 and 30 mg/day for weeks 4–7, or (group 4) placebo.

The placebo group comprised 83 women; each citalopram arm had 57 women. Most participants were 50 years or older (81%) and white (89%). A third of the women (34%) had a history of breast cancer. Nearly half the women (48%) had 4–9 hot flashes per day, another 38% had 10 or more per day, and 13% had less than 4 per day (13%). Mean baseline hot flash score and frequency were comparable between the groups.

The primary outcome, hot flash score, was measured with a daily diary. Secondary outcomes included data from Hot Flash Daily Interference and Profile of Mood States measures and from a symptom experience diary.

Women in the placebo group had a mean hot flash score reduction of 23%. Women in the 10 mg, 20 mg, and 30 mg citalopram groups had mean reductions of 49%, 50%, and 55%, respectively, with the differences relative to placebo being statistically significant for all three citalopram groups.

The mean reduction in hot flash frequency was 20% for the placebo group. The mean reductions for the 10-mg, 20- mg, and 30-mg citalopram groups were 46%, 43%, and 50%, respectively. Again all three comparisons to placebo were statistically significant.

The researchers also looked at quality of life measures. On the Profile of Mood States measure, women in the citalopram arms had greater improvement from baseline than did those in the placebo group on the tension/anxiety subscale, though the difference was only significant for the 20-mg citalopram group. Likewise, women in the citalopram arms had greater improvements from baseline than did those in the placebo group on the anger/hostility subscale, though the difference was only significant for the 10-mg arm.

On the Hot Flash Daily Interference Scale, women in the citalopram arms generally had greater improvements from baseline than did those in the placebo group on measures of work, social, leisure, sleep, mood, concentration, relationships, sexuality, enjoyment of life, and overall quality of life.

Women on any dose of citalopram also had significantly greater improvements in abnormal sweating, hot flash distress, and hot flash control than did women in the placebo group.

The authors reported no conflicts of interest.

Mean reductions in hot flash frequency were 46%–50% for citalopram and 20% for placebo. DR. BARTON

CHICAGO – Citalopram may be an effective option for reducing hot flashes, having performed twice as well as placebo in a randomized, placebo-controlled phase III trial conducted by the North Central Cancer Treatment Group.

“Hot flash relief can be obtained with as little as 10 mg/day citalopram,” Debra Barton, Ph.D., of the Mayo Clinic in Rochester, Minn., and her coauthors concluded in a poster reporting results of the trial at the annual meeting of the American Society of Clinical Oncology.

A selective serotonin reuptake inhibitor (SSRI), citalopram (Celexa) is approved for depression, but is also used for some other disorders.

Postmenopausal women who had a history of breast cancer or wanted to avoid hormones due to breast cancer risk were enrolled in the study. They had to have at least 14 hot flashes per week for at least 1 month. Endocrine therapy was allowed, if the woman was on a stable dose for at least 1 month. No other antidepressants or hot flash therapies were permitted.

All 254 participants kept a record of their hot flashes for 1 week before starting treatment, The investigators randomized the women into four groups that received either (group 1) 10 mg/day of citalopram on weeks 2–7, (group 2) 10 mg/day of citalopram during week 2 followed by 20 mg/day of citalopram for weeks 3–7, (group 3) 10 mg/day of citalopram during week 2 followed by 20 mg/day for week 3 and 30 mg/day for weeks 4–7, or (group 4) placebo.

The placebo group comprised 83 women; each citalopram arm had 57 women. Most participants were 50 years or older (81%) and white (89%). A third of the women (34%) had a history of breast cancer. Nearly half the women (48%) had 4–9 hot flashes per day, another 38% had 10 or more per day, and 13% had less than 4 per day (13%). Mean baseline hot flash score and frequency were comparable between the groups.

The primary outcome, hot flash score, was measured with a daily diary. Secondary outcomes included data from Hot Flash Daily Interference and Profile of Mood States measures and from a symptom experience diary.

Women in the placebo group had a mean hot flash score reduction of 23%. Women in the 10 mg, 20 mg, and 30 mg citalopram groups had mean reductions of 49%, 50%, and 55%, respectively, with the differences relative to placebo being statistically significant for all three citalopram groups.

The mean reduction in hot flash frequency was 20% for the placebo group. The mean reductions for the 10-mg, 20- mg, and 30-mg citalopram groups were 46%, 43%, and 50%, respectively. Again all three comparisons to placebo were statistically significant.

The researchers also looked at quality of life measures. On the Profile of Mood States measure, women in the citalopram arms had greater improvement from baseline than did those in the placebo group on the tension/anxiety subscale, though the difference was only significant for the 20-mg citalopram group. Likewise, women in the citalopram arms had greater improvements from baseline than did those in the placebo group on the anger/hostility subscale, though the difference was only significant for the 10-mg arm.

On the Hot Flash Daily Interference Scale, women in the citalopram arms generally had greater improvements from baseline than did those in the placebo group on measures of work, social, leisure, sleep, mood, concentration, relationships, sexuality, enjoyment of life, and overall quality of life.

Women on any dose of citalopram also had significantly greater improvements in abnormal sweating, hot flash distress, and hot flash control than did women in the placebo group.

The authors reported no conflicts of interest.

Mean reductions in hot flash frequency were 46%–50% for citalopram and 20% for placebo. DR. BARTON

CHICAGO – Citalopram may be an effective option for reducing hot flashes, having performed twice as well as placebo in a randomized, placebo-controlled phase III trial conducted by the North Central Cancer Treatment Group.

“Hot flash relief can be obtained with as little as 10 mg/day citalopram,” Debra Barton, Ph.D., of the Mayo Clinic in Rochester, Minn., and her coauthors concluded in a poster reporting results of the trial at the annual meeting of the American Society of Clinical Oncology.

A selective serotonin reuptake inhibitor (SSRI), citalopram (Celexa) is approved for depression, but is also used for some other disorders.

Postmenopausal women who had a history of breast cancer or wanted to avoid hormones due to breast cancer risk were enrolled in the study. They had to have at least 14 hot flashes per week for at least 1 month. Endocrine therapy was allowed, if the woman was on a stable dose for at least 1 month. No other antidepressants or hot flash therapies were permitted.

All 254 participants kept a record of their hot flashes for 1 week before starting treatment, The investigators randomized the women into four groups that received either (group 1) 10 mg/day of citalopram on weeks 2–7, (group 2) 10 mg/day of citalopram during week 2 followed by 20 mg/day of citalopram for weeks 3–7, (group 3) 10 mg/day of citalopram during week 2 followed by 20 mg/day for week 3 and 30 mg/day for weeks 4–7, or (group 4) placebo.

The placebo group comprised 83 women; each citalopram arm had 57 women. Most participants were 50 years or older (81%) and white (89%). A third of the women (34%) had a history of breast cancer. Nearly half the women (48%) had 4–9 hot flashes per day, another 38% had 10 or more per day, and 13% had less than 4 per day (13%). Mean baseline hot flash score and frequency were comparable between the groups.

The primary outcome, hot flash score, was measured with a daily diary. Secondary outcomes included data from Hot Flash Daily Interference and Profile of Mood States measures and from a symptom experience diary.

Women in the placebo group had a mean hot flash score reduction of 23%. Women in the 10 mg, 20 mg, and 30 mg citalopram groups had mean reductions of 49%, 50%, and 55%, respectively, with the differences relative to placebo being statistically significant for all three citalopram groups.

The mean reduction in hot flash frequency was 20% for the placebo group. The mean reductions for the 10-mg, 20- mg, and 30-mg citalopram groups were 46%, 43%, and 50%, respectively. Again all three comparisons to placebo were statistically significant.

The researchers also looked at quality of life measures. On the Profile of Mood States measure, women in the citalopram arms had greater improvement from baseline than did those in the placebo group on the tension/anxiety subscale, though the difference was only significant for the 20-mg citalopram group. Likewise, women in the citalopram arms had greater improvements from baseline than did those in the placebo group on the anger/hostility subscale, though the difference was only significant for the 10-mg arm.

On the Hot Flash Daily Interference Scale, women in the citalopram arms generally had greater improvements from baseline than did those in the placebo group on measures of work, social, leisure, sleep, mood, concentration, relationships, sexuality, enjoyment of life, and overall quality of life.

Women on any dose of citalopram also had significantly greater improvements in abnormal sweating, hot flash distress, and hot flash control than did women in the placebo group.

The authors reported no conflicts of interest.

Mean reductions in hot flash frequency were 46%–50% for citalopram and 20% for placebo. DR. BARTON

WASHINGTON – Even though the sleeping aid zolpidem does cross the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetrical and neonatal outcomes among women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes among a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of psychotropics.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

No statistically significant differences were found between the two groups in terms of obstetrical and neonatal outcomes. However, a trend toward preterm delivery and low-birth-weight infants was seen among women on zolpidem during pregnancy. “It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and her colleagues at Emory University's Women's Mental Health Program in Atlanta. Ms. Juric reported no conflicts of interest.

WASHINGTON – Even though the sleeping aid zolpidem does cross the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetrical and neonatal outcomes among women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes among a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of psychotropics.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

No statistically significant differences were found between the two groups in terms of obstetrical and neonatal outcomes. However, a trend toward preterm delivery and low-birth-weight infants was seen among women on zolpidem during pregnancy. “It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and her colleagues at Emory University's Women's Mental Health Program in Atlanta. Ms. Juric reported no conflicts of interest.

WASHINGTON – Even though the sleeping aid zolpidem does cross the placenta, use of the drug during pregnancy does not appear to significantly affect outcomes, a study of 45 women shows.

The study, presented as a poster at the annual meeting of the American Psychiatric Association, included pregnant women who were enrolled in a prospective study of the pharmacokinetics of psychotropic drugs during pregnancy and who were treated with zolpidem (Ambien) during pregnancy. Maternal diagnoses were determined using the Structured Clinical Interview for DSM-IV (SCID). Maternal and cord blood were obtained at delivery when possible.

The placental passage rate was calculated as the ratio of medication concentration in the umbilical cord plasma to that in maternal plasma. When umbilical cord concentrations were below the limit of detection (less than 4.0 ng/mL), this value was used for data analysis. This approach was thought to be conservative, erring toward overestimation of fetal exposure to zolpidem. When both maternal and umbilical plasma concentrations were less than the detection limit, the pair was excluded from the analysis.

Obstetrical and neonatal outcomes among women who had given birth to a live infant after taking zolpidem during pregnancy were compared with outcomes among a group of 45 women who were matched for age, race, level of education, SCID diagnosis, and pregnancy exposure to the same classes of psychotropics.

For women who took zolpidem during pregnancy, exposure by trimester included 38% in the first trimester, 56% in the second trimester, and 38% in the third trimester. The average zolpidem exposure during pregnancy was 14 weeks, and the average dose was 9 mg.

No statistically significant differences were found between the two groups in terms of obstetrical and neonatal outcomes. However, a trend toward preterm delivery and low-birth-weight infants was seen among women on zolpidem during pregnancy. “It is unclear if these outcomes were driven by zolpidem exposure and/or sleep disturbance or other pharmacological intervention in pregnancy,” wrote Sandra Juric and her colleagues at Emory University's Women's Mental Health Program in Atlanta. Ms. Juric reported no conflicts of interest.

WASHINGTON – Newer drugs aren't any better for migraine prophylaxis than are older treatments and might be worse choices for many patients when cost is a factor.

“There's no proof of increased efficacy with the newer drugs,” said Dr. Gretchen E. Tietjen, chair of the department of neurology at the University of Toledo (Ohio).

Topiramate (Topamax), a newer drug, has been compared with several other drugs in head-to-head, double-blind studies, including divalproex sodium, nadolol, propranolol, and amitriptyline, she said at the annual meeting of the American College of Physicians. “In these head-to-head studies, there was similar efficacy.”

Propranolol probably is the best-studied agent for migraine prevention and is Food and Drug Administration-approved for that indication. “There are–so far–no other drugs that have been shown to have better efficacy,” Dr. Tietjen said. However, because many of her patients have depression or asthma, two relative contraindications to using the drug, she prescribes it infrequently.

Open-label studies have suggested that, in patients who did not respond to propranolol alone or topiramate alone, the combination might be more effective, but more research is needed.

It's also important to consider potential side effects, Dr. Tietjen said. While topiramate doses of up to 100 mg are well tolerated, it has several uncommon but potentially serious side effects, including paresthesias of the extremities, loss of appetite, depression, and confusion.

Cost also is a consideration. In her own informal survey of a local pharmacy, the monthly cost of the typical dosage of amitriptyline was $10, propranolol was $53, divalproex sodium was $128, and topiramate was $235.

“So there's really a difference [in cost], especially when you don't see much difference in efficacy,” Dr. Tietjen said.

In a 2000 evidence-based review by the U.S. Headache Consortium–made up of several specialty societies–group I drugs were considered to have medium to high efficacy with good strength of evidence and mild to moderate side effects.

These included amitriptyline, propanolol, timolol, and divalproex sodium. All but amitriptyline are FDA approved for migraine.

Group II medications either had lower efficacy or limited strength of evidence. This group included several β-blockers (nadolol, metoprolol, atenolol), calcium-channel blockers (verapamil, nifedipine), an anticonvulsant (gabapentin), nonsteroidal anti-inflammatory drugs (naproxen sodium), magnesium, and vitamin B. (Topiramate had not been approved when this review was published.)

Med Overuse or Analgesic Rebound Headache

The International Headache Society's most recent criteria for medication overuse headache include a headache present for more than 15 days/month, regular use for at least 3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache, and a headache that has developed or markedly worsened during medication use (Cephalalgia 2004;24[suppl 1]:9–160).

Educating patients about the potential for developing medication overuse headaches and monitoring their medications are probably the most useful tools in treating these chronic headaches, Dr. Tietjen said.

Discontinuation of the use of abortive medications is the key to treatment. “For somebody you suspect of medication overuse headache … you want to stop the medication they're using. Whether you do it gradually or abruptly depends on the medication and depends on the patient,” she said.

She also recommended starting the patient on a prophylactic medication. Several transition regimens have been suggested, though these have not been well studied. Dr. Tietjen often uses dihydroergotamine 0.5–1 mg every 8 hours for 2–3 days. This is a particularly good option for hospital inpatients who are stopping opioids and butalbital, she said.

Oral Contraceptives for Hormonal Migraines

Hormonal headaches include pure menstrual headaches and those related to the menstrual cycle. Pure menstrual migraines occur in a consistent relationship with menstruation and do not occur at other times of the month. It's estimated that about 15% of women with migraine have the pure menstrual variety. Menstruation-related migraines occur not only in a consistent relationship with menstruation but also at other times of the month. An estimated 60% of women migraineurs have this type.

“Studies have really strongly suggested that menstrual migraines are generally more severe, more intractable to therapy, [and] usually have more associated symptoms, like nausea and sensitivity to light and sound,” Dr. Tietjen said.

In studies that have looked at low-dose (30–35 mcg ethinyl estradiol) oral contraceptives for the treatment of menstrual headaches, half to two-thirds of women reported no change, a quarter to a third reported migraine worsening, and only about 10% reported improvement.

Triptans appear to be effective for both menstrual and nonmenstrual headaches. Analgesics, such as naproxen sodium, also appear to be effective.

Several studies have looked at triptans for short-term prevention of predictable menstrual headaches. Naratriptan 1 mg or frovatriptan 2.5 mg administered twice daily for 6 days/month have been shown to be effective and well tolerated.

Both the World Health Organization and the American College of Obstetricians and Gynecologists have published consensus guidelines addressing migraine. Both recommend that women with migraine who are older than 35 years generally should not use oral contraceptives nor should women of any age with migraine with aura.

In general, Dr. Tietjen does not use oral contraceptives to treat menstrual migraines. If a migraine patient wants to use oral contraceptives, she recommends a low-dose monophasic regimen.

Dr. Tietjen reported that she has received research support from GlaxoSmithKline Inc. and NMT Medical Inc.

WASHINGTON – Newer drugs aren't any better for migraine prophylaxis than are older treatments and might be worse choices for many patients when cost is a factor.

“There's no proof of increased efficacy with the newer drugs,” said Dr. Gretchen E. Tietjen, chair of the department of neurology at the University of Toledo (Ohio).

Topiramate (Topamax), a newer drug, has been compared with several other drugs in head-to-head, double-blind studies, including divalproex sodium, nadolol, propranolol, and amitriptyline, she said at the annual meeting of the American College of Physicians. “In these head-to-head studies, there was similar efficacy.”

Propranolol probably is the best-studied agent for migraine prevention and is Food and Drug Administration-approved for that indication. “There are–so far–no other drugs that have been shown to have better efficacy,” Dr. Tietjen said. However, because many of her patients have depression or asthma, two relative contraindications to using the drug, she prescribes it infrequently.

Open-label studies have suggested that, in patients who did not respond to propranolol alone or topiramate alone, the combination might be more effective, but more research is needed.

It's also important to consider potential side effects, Dr. Tietjen said. While topiramate doses of up to 100 mg are well tolerated, it has several uncommon but potentially serious side effects, including paresthesias of the extremities, loss of appetite, depression, and confusion.

Cost also is a consideration. In her own informal survey of a local pharmacy, the monthly cost of the typical dosage of amitriptyline was $10, propranolol was $53, divalproex sodium was $128, and topiramate was $235.

“So there's really a difference [in cost], especially when you don't see much difference in efficacy,” Dr. Tietjen said.

In a 2000 evidence-based review by the U.S. Headache Consortium–made up of several specialty societies–group I drugs were considered to have medium to high efficacy with good strength of evidence and mild to moderate side effects.

These included amitriptyline, propanolol, timolol, and divalproex sodium. All but amitriptyline are FDA approved for migraine.

Group II medications either had lower efficacy or limited strength of evidence. This group included several β-blockers (nadolol, metoprolol, atenolol), calcium-channel blockers (verapamil, nifedipine), an anticonvulsant (gabapentin), nonsteroidal anti-inflammatory drugs (naproxen sodium), magnesium, and vitamin B. (Topiramate had not been approved when this review was published.)

Med Overuse or Analgesic Rebound Headache

The International Headache Society's most recent criteria for medication overuse headache include a headache present for more than 15 days/month, regular use for at least 3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache, and a headache that has developed or markedly worsened during medication use (Cephalalgia 2004;24[suppl 1]:9–160).

Educating patients about the potential for developing medication overuse headaches and monitoring their medications are probably the most useful tools in treating these chronic headaches, Dr. Tietjen said.

Discontinuation of the use of abortive medications is the key to treatment. “For somebody you suspect of medication overuse headache … you want to stop the medication they're using. Whether you do it gradually or abruptly depends on the medication and depends on the patient,” she said.

She also recommended starting the patient on a prophylactic medication. Several transition regimens have been suggested, though these have not been well studied. Dr. Tietjen often uses dihydroergotamine 0.5–1 mg every 8 hours for 2–3 days. This is a particularly good option for hospital inpatients who are stopping opioids and butalbital, she said.

Oral Contraceptives for Hormonal Migraines

Hormonal headaches include pure menstrual headaches and those related to the menstrual cycle. Pure menstrual migraines occur in a consistent relationship with menstruation and do not occur at other times of the month. It's estimated that about 15% of women with migraine have the pure menstrual variety. Menstruation-related migraines occur not only in a consistent relationship with menstruation but also at other times of the month. An estimated 60% of women migraineurs have this type.

“Studies have really strongly suggested that menstrual migraines are generally more severe, more intractable to therapy, [and] usually have more associated symptoms, like nausea and sensitivity to light and sound,” Dr. Tietjen said.

In studies that have looked at low-dose (30–35 mcg ethinyl estradiol) oral contraceptives for the treatment of menstrual headaches, half to two-thirds of women reported no change, a quarter to a third reported migraine worsening, and only about 10% reported improvement.

Triptans appear to be effective for both menstrual and nonmenstrual headaches. Analgesics, such as naproxen sodium, also appear to be effective.

Several studies have looked at triptans for short-term prevention of predictable menstrual headaches. Naratriptan 1 mg or frovatriptan 2.5 mg administered twice daily for 6 days/month have been shown to be effective and well tolerated.

Both the World Health Organization and the American College of Obstetricians and Gynecologists have published consensus guidelines addressing migraine. Both recommend that women with migraine who are older than 35 years generally should not use oral contraceptives nor should women of any age with migraine with aura.

In general, Dr. Tietjen does not use oral contraceptives to treat menstrual migraines. If a migraine patient wants to use oral contraceptives, she recommends a low-dose monophasic regimen.

Dr. Tietjen reported that she has received research support from GlaxoSmithKline Inc. and NMT Medical Inc.

WASHINGTON – Newer drugs aren't any better for migraine prophylaxis than are older treatments and might be worse choices for many patients when cost is a factor.

“There's no proof of increased efficacy with the newer drugs,” said Dr. Gretchen E. Tietjen, chair of the department of neurology at the University of Toledo (Ohio).

Topiramate (Topamax), a newer drug, has been compared with several other drugs in head-to-head, double-blind studies, including divalproex sodium, nadolol, propranolol, and amitriptyline, she said at the annual meeting of the American College of Physicians. “In these head-to-head studies, there was similar efficacy.”

Propranolol probably is the best-studied agent for migraine prevention and is Food and Drug Administration-approved for that indication. “There are–so far–no other drugs that have been shown to have better efficacy,” Dr. Tietjen said. However, because many of her patients have depression or asthma, two relative contraindications to using the drug, she prescribes it infrequently.

Open-label studies have suggested that, in patients who did not respond to propranolol alone or topiramate alone, the combination might be more effective, but more research is needed.

It's also important to consider potential side effects, Dr. Tietjen said. While topiramate doses of up to 100 mg are well tolerated, it has several uncommon but potentially serious side effects, including paresthesias of the extremities, loss of appetite, depression, and confusion.

Cost also is a consideration. In her own informal survey of a local pharmacy, the monthly cost of the typical dosage of amitriptyline was $10, propranolol was $53, divalproex sodium was $128, and topiramate was $235.

“So there's really a difference [in cost], especially when you don't see much difference in efficacy,” Dr. Tietjen said.

In a 2000 evidence-based review by the U.S. Headache Consortium–made up of several specialty societies–group I drugs were considered to have medium to high efficacy with good strength of evidence and mild to moderate side effects.

These included amitriptyline, propanolol, timolol, and divalproex sodium. All but amitriptyline are FDA approved for migraine.

Group II medications either had lower efficacy or limited strength of evidence. This group included several β-blockers (nadolol, metoprolol, atenolol), calcium-channel blockers (verapamil, nifedipine), an anticonvulsant (gabapentin), nonsteroidal anti-inflammatory drugs (naproxen sodium), magnesium, and vitamin B. (Topiramate had not been approved when this review was published.)

Med Overuse or Analgesic Rebound Headache

The International Headache Society's most recent criteria for medication overuse headache include a headache present for more than 15 days/month, regular use for at least 3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache, and a headache that has developed or markedly worsened during medication use (Cephalalgia 2004;24[suppl 1]:9–160).

Educating patients about the potential for developing medication overuse headaches and monitoring their medications are probably the most useful tools in treating these chronic headaches, Dr. Tietjen said.

Discontinuation of the use of abortive medications is the key to treatment. “For somebody you suspect of medication overuse headache … you want to stop the medication they're using. Whether you do it gradually or abruptly depends on the medication and depends on the patient,” she said.

She also recommended starting the patient on a prophylactic medication. Several transition regimens have been suggested, though these have not been well studied. Dr. Tietjen often uses dihydroergotamine 0.5–1 mg every 8 hours for 2–3 days. This is a particularly good option for hospital inpatients who are stopping opioids and butalbital, she said.

Oral Contraceptives for Hormonal Migraines

Hormonal headaches include pure menstrual headaches and those related to the menstrual cycle. Pure menstrual migraines occur in a consistent relationship with menstruation and do not occur at other times of the month. It's estimated that about 15% of women with migraine have the pure menstrual variety. Menstruation-related migraines occur not only in a consistent relationship with menstruation but also at other times of the month. An estimated 60% of women migraineurs have this type.

“Studies have really strongly suggested that menstrual migraines are generally more severe, more intractable to therapy, [and] usually have more associated symptoms, like nausea and sensitivity to light and sound,” Dr. Tietjen said.

In studies that have looked at low-dose (30–35 mcg ethinyl estradiol) oral contraceptives for the treatment of menstrual headaches, half to two-thirds of women reported no change, a quarter to a third reported migraine worsening, and only about 10% reported improvement.

Triptans appear to be effective for both menstrual and nonmenstrual headaches. Analgesics, such as naproxen sodium, also appear to be effective.

Several studies have looked at triptans for short-term prevention of predictable menstrual headaches. Naratriptan 1 mg or frovatriptan 2.5 mg administered twice daily for 6 days/month have been shown to be effective and well tolerated.

Both the World Health Organization and the American College of Obstetricians and Gynecologists have published consensus guidelines addressing migraine. Both recommend that women with migraine who are older than 35 years generally should not use oral contraceptives nor should women of any age with migraine with aura.

In general, Dr. Tietjen does not use oral contraceptives to treat menstrual migraines. If a migraine patient wants to use oral contraceptives, she recommends a low-dose monophasic regimen.

Dr. Tietjen reported that she has received research support from GlaxoSmithKline Inc. and NMT Medical Inc.

WASHINGTON – People with intellectual disabilities do exhibit pathological gambling behavior, and gambling in general is common in this population, a study of 79 people in the Las Vegas area shows.

Two of the study participants (2.5%) met DSM-IV-TR criteria for pathological gambling. This rate is comparable with rates identified for the state of Nevada, which range from 2.7% to 4.3%. In addition, five study participants met the criteria for problem gambling (6.3%), which also was comparable with the rates identified for Nevada (2.2%–3.6%), Dr. Coni Kalinowski of the University of Nevada, Las Vegas, reported at the annual meeting of the American Psychiatric Association.

For this survey, the researchers modified the Gambling Symptom Assessment Scale (G-SAS) and the Structured Clinical Interview for Pathological Gambling (SGI-PG) to make them more suitable for individuals with intellectual disability. The researchers also performed a health screening to identify psychiatric diagnoses, common medical/neurological conditions, and any psychotropic medications used.

Participants in this study included those aged 21 years and older who had a documented intellectual disability with full-scale IQ of 75 or less. Intellectual disabilities include mental retardation from any cause, autism spectrum disorders, refractory epilepsy, cerebral palsy, and permanent cognitive impairment occurring before the age of 18. These individuals had to be their own guardians (because of state requirements). All participants were clients of a dual diagnosis clinic in Las Vegas.

In all, data were collected for 79 individuals (53% female). Most were white (66%), followed by African American (23%), Hispanic/Latino (9%), and Asian and Pacific Islander (1% each). The majority of participants were younger than 40 years (70%). Overall, 89% reported ever gambling and 71% reported gambling in the past year. These numbers were comparable with the Nevada population.

Most of the problem gamblers (71%) were between the ages of 21 and 39 years. Most of the problem gamblers were female (86%). Problem gamblers (those who met criteria for pathological or problem gambling) differed from their nonproblem gambling counterparts in several ways. Problem gamblers were more likely to live in the family home (57%), compared with other study subjects (18%). Most of the participants without problem gambling (60%) lived in group residences. None of the problem gamblers lived independently, compared with almost a quarter of those without problem gambling (24%).

Problem gamblers were somewhat more likely to use highly accessible venues, like grocery stores. Problem gamblers also were more likely to gamble alone–43% versus 24% for nonproblem gamblers. Those without problem gambling were more likely to gamble with family. “While both groups frequently gambled with friends or staff, we also learned that very often group-home staff would use gambling as a positive reinforcer,” Dr. Kalinowski said.

Nearly all gamblers had played slots or electronic game machines. In addition, scratch cards and bingo were common among all gamblers. Both groups predominantly gambled $5-$20 per episode.

However, problem gamblers (29%) were more likely to have wagered larger amounts than those without problem gambling (8%).

None of the problem gamblers reported using alcohol while gambling. Roughly a quarter of participants admitted to gambling more money than they wanted, thinking about gambling when they didn't want to, or borrowing money to gamble, Dr. Kalinowski said.

These individuals are often more dependent on others, so that gambling behavior may be significantly determined by opportunity or the gambling habits of others.

In addition, externally imposed supports and controls may limit the life consequences of problem gambling in this population but may not limit subjective distress. Gambling might even have benefits for individuals with intellectual disabilities by offering low-demand socialization, nonstigmatized recreation, and a fully “adult activity,” she said.

Dr. Kalinowski reported that she had no relevant conflicts of interest.

WASHINGTON – People with intellectual disabilities do exhibit pathological gambling behavior, and gambling in general is common in this population, a study of 79 people in the Las Vegas area shows.

Two of the study participants (2.5%) met DSM-IV-TR criteria for pathological gambling. This rate is comparable with rates identified for the state of Nevada, which range from 2.7% to 4.3%. In addition, five study participants met the criteria for problem gambling (6.3%), which also was comparable with the rates identified for Nevada (2.2%–3.6%), Dr. Coni Kalinowski of the University of Nevada, Las Vegas, reported at the annual meeting of the American Psychiatric Association.

For this survey, the researchers modified the Gambling Symptom Assessment Scale (G-SAS) and the Structured Clinical Interview for Pathological Gambling (SGI-PG) to make them more suitable for individuals with intellectual disability. The researchers also performed a health screening to identify psychiatric diagnoses, common medical/neurological conditions, and any psychotropic medications used.

Participants in this study included those aged 21 years and older who had a documented intellectual disability with full-scale IQ of 75 or less. Intellectual disabilities include mental retardation from any cause, autism spectrum disorders, refractory epilepsy, cerebral palsy, and permanent cognitive impairment occurring before the age of 18. These individuals had to be their own guardians (because of state requirements). All participants were clients of a dual diagnosis clinic in Las Vegas.

In all, data were collected for 79 individuals (53% female). Most were white (66%), followed by African American (23%), Hispanic/Latino (9%), and Asian and Pacific Islander (1% each). The majority of participants were younger than 40 years (70%). Overall, 89% reported ever gambling and 71% reported gambling in the past year. These numbers were comparable with the Nevada population.

Most of the problem gamblers (71%) were between the ages of 21 and 39 years. Most of the problem gamblers were female (86%). Problem gamblers (those who met criteria for pathological or problem gambling) differed from their nonproblem gambling counterparts in several ways. Problem gamblers were more likely to live in the family home (57%), compared with other study subjects (18%). Most of the participants without problem gambling (60%) lived in group residences. None of the problem gamblers lived independently, compared with almost a quarter of those without problem gambling (24%).

Problem gamblers were somewhat more likely to use highly accessible venues, like grocery stores. Problem gamblers also were more likely to gamble alone–43% versus 24% for nonproblem gamblers. Those without problem gambling were more likely to gamble with family. “While both groups frequently gambled with friends or staff, we also learned that very often group-home staff would use gambling as a positive reinforcer,” Dr. Kalinowski said.

Nearly all gamblers had played slots or electronic game machines. In addition, scratch cards and bingo were common among all gamblers. Both groups predominantly gambled $5-$20 per episode.

However, problem gamblers (29%) were more likely to have wagered larger amounts than those without problem gambling (8%).

None of the problem gamblers reported using alcohol while gambling. Roughly a quarter of participants admitted to gambling more money than they wanted, thinking about gambling when they didn't want to, or borrowing money to gamble, Dr. Kalinowski said.

These individuals are often more dependent on others, so that gambling behavior may be significantly determined by opportunity or the gambling habits of others.

In addition, externally imposed supports and controls may limit the life consequences of problem gambling in this population but may not limit subjective distress. Gambling might even have benefits for individuals with intellectual disabilities by offering low-demand socialization, nonstigmatized recreation, and a fully “adult activity,” she said.

Dr. Kalinowski reported that she had no relevant conflicts of interest.

WASHINGTON – People with intellectual disabilities do exhibit pathological gambling behavior, and gambling in general is common in this population, a study of 79 people in the Las Vegas area shows.

Two of the study participants (2.5%) met DSM-IV-TR criteria for pathological gambling. This rate is comparable with rates identified for the state of Nevada, which range from 2.7% to 4.3%. In addition, five study participants met the criteria for problem gambling (6.3%), which also was comparable with the rates identified for Nevada (2.2%–3.6%), Dr. Coni Kalinowski of the University of Nevada, Las Vegas, reported at the annual meeting of the American Psychiatric Association.

For this survey, the researchers modified the Gambling Symptom Assessment Scale (G-SAS) and the Structured Clinical Interview for Pathological Gambling (SGI-PG) to make them more suitable for individuals with intellectual disability. The researchers also performed a health screening to identify psychiatric diagnoses, common medical/neurological conditions, and any psychotropic medications used.

Participants in this study included those aged 21 years and older who had a documented intellectual disability with full-scale IQ of 75 or less. Intellectual disabilities include mental retardation from any cause, autism spectrum disorders, refractory epilepsy, cerebral palsy, and permanent cognitive impairment occurring before the age of 18. These individuals had to be their own guardians (because of state requirements). All participants were clients of a dual diagnosis clinic in Las Vegas.

In all, data were collected for 79 individuals (53% female). Most were white (66%), followed by African American (23%), Hispanic/Latino (9%), and Asian and Pacific Islander (1% each). The majority of participants were younger than 40 years (70%). Overall, 89% reported ever gambling and 71% reported gambling in the past year. These numbers were comparable with the Nevada population.

Most of the problem gamblers (71%) were between the ages of 21 and 39 years. Most of the problem gamblers were female (86%). Problem gamblers (those who met criteria for pathological or problem gambling) differed from their nonproblem gambling counterparts in several ways. Problem gamblers were more likely to live in the family home (57%), compared with other study subjects (18%). Most of the participants without problem gambling (60%) lived in group residences. None of the problem gamblers lived independently, compared with almost a quarter of those without problem gambling (24%).

Problem gamblers were somewhat more likely to use highly accessible venues, like grocery stores. Problem gamblers also were more likely to gamble alone–43% versus 24% for nonproblem gamblers. Those without problem gambling were more likely to gamble with family. “While both groups frequently gambled with friends or staff, we also learned that very often group-home staff would use gambling as a positive reinforcer,” Dr. Kalinowski said.

Nearly all gamblers had played slots or electronic game machines. In addition, scratch cards and bingo were common among all gamblers. Both groups predominantly gambled $5-$20 per episode.

However, problem gamblers (29%) were more likely to have wagered larger amounts than those without problem gambling (8%).

None of the problem gamblers reported using alcohol while gambling. Roughly a quarter of participants admitted to gambling more money than they wanted, thinking about gambling when they didn't want to, or borrowing money to gamble, Dr. Kalinowski said.

These individuals are often more dependent on others, so that gambling behavior may be significantly determined by opportunity or the gambling habits of others.

In addition, externally imposed supports and controls may limit the life consequences of problem gambling in this population but may not limit subjective distress. Gambling might even have benefits for individuals with intellectual disabilities by offering low-demand socialization, nonstigmatized recreation, and a fully “adult activity,” she said.

Dr. Kalinowski reported that she had no relevant conflicts of interest.