I found Dr. Scott Freeman’s article on suicide prevention (“Suicide assessment: Targeting acute risk factors,” Current Psychiatry, January 2012, p. 52-57) to be bold and courageous. Two of the 6 suicide risk factors he described are related to anxiety symptomatology: panic attacks and psychic anxiety. In the case study, Mr. L was prescribed clonazepam, a benzodiazepine, despite his history of comorbid alcohol abuse. Often, patients with substance abuse have related anxiety disorders—including posttraumatic stress disorder—and management with selective serotonin reuptake inhibitors (SSRIs) is not sufficient.

Because clinicians are hesitant to prescribe benzodiazepines to patients with a substance abuse history, patients often are forced to purchase these medications on the street or feel compelled to relapse to substance abuse in a frantic, albeit misguided, effort to contain their crippling symptoms. Even in inpatient drug rehabilitation settings, benzodiazepines often are not an option because they are not allowed. The “safer” SSRIs may be more dangerous when given to substance abusers in whom a comorbid mood disorder often is missed.

Current Psychiatry has never been shy in addressing the truth or uncomfortable issues in our complex field. Do we have the courage to open this up for dialogue and conversation?

Robert Barris, MD
Attending Psychiatrist
Nassau University Medical Center
East Meadow, NY

I found Dr. Scott Freeman’s article on suicide prevention (“Suicide assessment: Targeting acute risk factors,” Current Psychiatry, January 2012, p. 52-57) to be bold and courageous. Two of the 6 suicide risk factors he described are related to anxiety symptomatology: panic attacks and psychic anxiety. In the case study, Mr. L was prescribed clonazepam, a benzodiazepine, despite his history of comorbid alcohol abuse. Often, patients with substance abuse have related anxiety disorders—including posttraumatic stress disorder—and management with selective serotonin reuptake inhibitors (SSRIs) is not sufficient.

Because clinicians are hesitant to prescribe benzodiazepines to patients with a substance abuse history, patients often are forced to purchase these medications on the street or feel compelled to relapse to substance abuse in a frantic, albeit misguided, effort to contain their crippling symptoms. Even in inpatient drug rehabilitation settings, benzodiazepines often are not an option because they are not allowed. The “safer” SSRIs may be more dangerous when given to substance abusers in whom a comorbid mood disorder often is missed.

Current Psychiatry has never been shy in addressing the truth or uncomfortable issues in our complex field. Do we have the courage to open this up for dialogue and conversation?

Robert Barris, MD
Attending Psychiatrist
Nassau University Medical Center
East Meadow, NY

I found Dr. Scott Freeman’s article on suicide prevention (“Suicide assessment: Targeting acute risk factors,” Current Psychiatry, January 2012, p. 52-57) to be bold and courageous. Two of the 6 suicide risk factors he described are related to anxiety symptomatology: panic attacks and psychic anxiety. In the case study, Mr. L was prescribed clonazepam, a benzodiazepine, despite his history of comorbid alcohol abuse. Often, patients with substance abuse have related anxiety disorders—including posttraumatic stress disorder—and management with selective serotonin reuptake inhibitors (SSRIs) is not sufficient.

Because clinicians are hesitant to prescribe benzodiazepines to patients with a substance abuse history, patients often are forced to purchase these medications on the street or feel compelled to relapse to substance abuse in a frantic, albeit misguided, effort to contain their crippling symptoms. Even in inpatient drug rehabilitation settings, benzodiazepines often are not an option because they are not allowed. The “safer” SSRIs may be more dangerous when given to substance abusers in whom a comorbid mood disorder often is missed.

Current Psychiatry has never been shy in addressing the truth or uncomfortable issues in our complex field. Do we have the courage to open this up for dialogue and conversation?

Robert Barris, MD
Attending Psychiatrist
Nassau University Medical Center
East Meadow, NY

Binge eating is consumption of an unusually large amount of food coupled with a feeling of loss of control over eating. Binge eating disorder (BED) is characterized by recurrent episodes of binge eating without inappropriate compensatory behaviors (eg, self-induced vomiting, misuse of laxatives, diuretics, or other agents, excessive exercise).¹ It is the most common eating disorder in the United States, with a lifetime prevalence of approximately 3.5% in women and 2% in men.² The diagnosis falls within the DSM-IV-TR category of eating disorders not otherwise specified,¹ but clinicians often view it as a distinct clinical phenomenon. In DSM-IV-TR, an individual would meet criteria for BED if he or she engages in regular binge eating behavior in the absence of recurrent compensatory behaviors ≥2 days per week over 6 months.¹ Proposed changes for DSM-5 recognize a distinct BED diagnosis, reduce the frequency criterion to once per week and the duration criterion to the past 3 months, and shift the focus from binge days to binge episodes (Table 1).³

Table 1

Proposed DSM-5 criteria for binge eating disorder

BED can occur in individuals of all body mass indices (BMI), but is common among individuals who are overweight or obese as well as those with depression or type 2 diabetes; BED can complicate treatment of these conditions.^2,4,5 Primary treatment goals are:

• abstinence from binge eating
• improved psychological functioning
• appropriate weight regulation in overweight patients.

We report on 3 approaches to BED treatment: medication only, behavioral intervention only, and medication plus behavioral intervention. This article provides insights about emerging changes in diagnostic criteria for BED as well as evidence-informed treatment options and recommendations.

The evidence base

We conducted a review of 23 BED studies: 7 medication only, 5 medication plus behavioral, and 11 behavioral only. We focused on studies conducted since September 2005 that included binge frequency, weight, and depression as primary outcomes (see Berkman et al⁶ for a review of BED treatment studies before 2005). The studies included 2,527 participants (2,216 women and 311 men). Although the sex distribution of BED in the general population tends to slightly favor women,² the proportion of women presenting for treatment generally is considerably higher than that of men. In studies that reported on race and/or ethnicity, 1,639 participants were identified as white, 191 as African American, 25 as Hispanic, 2 as Asian, 1 as Native American, and 25 as “other.” Ages ranged from 18 to 77.

Several medications are effective

In placebo-controlled studies, a high-dose selective serotonin reuptake inhibitor (escitalopram⁷), 2 anticonvulsants (zonisamide⁸ and topiramate⁹), a selective norepinephrine reuptake inhibitor (atomoxetine¹⁰), and an appetite suppressant (sibutramine¹¹) were associated with significant decreases in binge eating frequency, weight, and BMI in overweight/obese patients diagnosed with BED (Table 2). In an open-label trial, memantine—a N-methyl-D-aspartate receptor antagonist often used to treat symptoms of Alzheimer’s disease—was associated with a significant reduction in binge eating but no change in weight.¹² Lamotrigine was not significantly different from placebo in reducing binge eating or weight, but showed promise in reducing metabolic parameters such as glucose and triglyceride levels commonly associated with obesity and type 2 diabetes.¹³ Because BED often is comorbid with obesity and type 2 diabetes, lamotrigine augmentation when treating obese individuals with BED warrants further investigation. As with any pharmacologic agent, carefully consider potential side effects and interactions with other drugs before prescribing medications for BED. Informing patients of potential side effects is crucial for patient safety and accuracy of the data collected in well-controlled treatment studies.

Table 2

Pharmacotherapy for binge eating disorder

CBT vs other behavioral approaches

Cognitive-behavioral therapy (CBT), which focuses on identifying and modifying unhealthy thoughts that maintain disordered eating behaviors, is the most widely studied behavioral intervention for BED. Other studied treatments include interpersonal psychotherapy (IPT), motivational interviewing (MI), and structured behavioral weight loss (BWL) (Table 3).^14-24 IPT is a psychodynamically based, time-limited treatment that focuses on the interpersonal context of the disorder and on building interpersonal skills. MI emphasizes exploring and resolving ambivalence about treatment, and works to facilitate change through motivational processes. BWL is centered on making dietary and physical activity changes to achieve weight loss. Behavioral treatments have been delivered in various formats, such as an individual or group setting, by electronic interface, and via self-help approaches. Most studies compared active treatment to a control group, but some compared active treatments head-to-head.

Table 3

CBT and other behavioral interventions for BED

Studies found that CBT and IPT are effective in reducing the frequency of binge eating, whether measured by the number of binge eating episodes or days a patient reports having engaged in binge eating.^14-23 However, some studies suggested that CBT can help a substantial number of patients achieve abstinence from binge eating.^16,20 Adding MI to a self-help approach may improve binge eating outcomes,²⁴ and binge eating can be successfully reduced using individual, group, and CD-ROM delivery formats.²¹ In direct comparisons, individual CBT outperformed group CBT in helping patients recover from BED (ie, no longer meeting diagnostic criteria),¹⁹ and CBT delivered via guided self-help outperformed BWL in helping patients achieve remission.¹⁸

Psychological features of BED typically include low levels of cognitive restraint and high levels of disinhibition, hunger, and shape and weight concerns. Improvements in these psychological measures were observed with CBT,^15-20,22 IPT,²² and MI.²⁴ In direct comparisons, self-help CBT demonstrated greater reductions in perceived hunger and disinhibition than self-help BWL,¹⁸ and individual CBT outperformed group CBT in reducing shape and weight concerns.¹⁹ Isolated studies reported improvements in depression after self-help CBT¹⁸ and MI,²⁴ and sustained improvements²² after group CBT (6 months) and group IPT (12 months). Additional research is needed to determine whether CBT crafted specifically for BED improves self-rated depression or if enhancements targeting depressive symptoms are required.

The impact of behavioral interventions on weight in overweight patients has been mixed. Although some CBT studies reported a substantial decrease in weight,^17,19 others suggested that weight loss among patients treated with CBT is not superior to those in a wait-list control group¹⁶ or is not significant over the course of treatment.^20,21 The impact of BWL on weight outcomes in BED also has been unimpressive: after 12 weeks, self-help BWL was no better than self-help CBT in reducing BMI¹⁸; after 16 weeks, BWL was better than CBT and IPT in achieving clinically significant (≥5%) weight loss, but this advantage was not sustained at 1- and 2-year follow-up.²³ It is difficult to determine why successfully treated BED patients fail to lose weight because one would expect decreases in binge eating to lead to weight loss. It is possible that calories previously consumed during binge eating episodes are distributed over non-binge meals or that patients label binges and non-binge meals differently as a result of treatment.

Combining treatments

BED patients often are treated with a combination of psychotherapy and pharmacotherapy (Table 4).^25-29 When added to CBT, topiramate was associated with improvements in weight and some psychological outcomes,^25,26 but fluoxetine was not.^27,28 Direct comparisons also showed that CBT, alone or combined with fluoxetine, was better than fluoxetine alone in reducing binge eating.²⁷ When combined with an individualized hypocaloric diet, the anti-obesity medication orlistat reduced weight in obese BED patients but had no appreciable effect on binge eating.²⁹ Collectively, the studies we reviewed suggested that combining medication and CBT may improve binge eating and weight loss outcomes; however, additional trials are necessary to determine more definitively which medications combined with CBT are best at producing sustained weight loss while reducing binge eating frequency.

Table 4

Combining medication with behavioral interventions for BED

Recommendations

Evidence suggests that pharmacotherapy and CBT—alone or in combination—are effective in reducing binge eating, and pharmacotherapy is effective in reducing weight in overweight individuals with BED. More research is needed for IPT and MI. It is unclear which medications provide the greatest benefit in terms of binge eating remission; however, pharmacotherapy has a clear advantage in facilitating short-term weight loss. Also, all BED patients should receive medical management to address possible complications such as hypertension or type 2 diabetes. In addition to reducing binge eating, CBT can improve related psychological comorbidities (eg, eating-related psychopathology and depression) and may have additional benefit when combined with pharmacotherapy.

In light of these findings, we recommend augmenting psychotherapeutic care with pharmacotherapy and medical management to address all relevant psychological and medical domains. Future investigations should address the benefits of coordinated psychological and medical care and evaluate how to maintain treatment gains.

Related Resources

• Binge Eating Disorder Association. www.bedaonline.com.
• Brownley KA, Berkman ND, Sedway JA, et al. Binge eating disorder treatment: a systematic review of randomized controlled trials. Int J Eat Disord. 2007;40(4):337-348.

Drug Brand Names

• Atomoxetine • Strattera
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Lamotrigine • Lamictal
• Memantine • Namenda
• Orlistat • Alli, Xenical
• Sertraline • Zoloft
• Sibutramine • Meridia
• Topiramate • Topamax, Topiragen
• Zonisamide • Zonegram

Disclosures

Dr. Peat receives a post-doctoral trainee grant from the National Institutes of Health.

Drs. Brownley, Berkman, and Bulik report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Binge eating is consumption of an unusually large amount of food coupled with a feeling of loss of control over eating. Binge eating disorder (BED) is characterized by recurrent episodes of binge eating without inappropriate compensatory behaviors (eg, self-induced vomiting, misuse of laxatives, diuretics, or other agents, excessive exercise).¹ It is the most common eating disorder in the United States, with a lifetime prevalence of approximately 3.5% in women and 2% in men.² The diagnosis falls within the DSM-IV-TR category of eating disorders not otherwise specified,¹ but clinicians often view it as a distinct clinical phenomenon. In DSM-IV-TR, an individual would meet criteria for BED if he or she engages in regular binge eating behavior in the absence of recurrent compensatory behaviors ≥2 days per week over 6 months.¹ Proposed changes for DSM-5 recognize a distinct BED diagnosis, reduce the frequency criterion to once per week and the duration criterion to the past 3 months, and shift the focus from binge days to binge episodes (Table 1).³

Table 1

Proposed DSM-5 criteria for binge eating disorder

BED can occur in individuals of all body mass indices (BMI), but is common among individuals who are overweight or obese as well as those with depression or type 2 diabetes; BED can complicate treatment of these conditions.^2,4,5 Primary treatment goals are:

• abstinence from binge eating
• improved psychological functioning
• appropriate weight regulation in overweight patients.

We report on 3 approaches to BED treatment: medication only, behavioral intervention only, and medication plus behavioral intervention. This article provides insights about emerging changes in diagnostic criteria for BED as well as evidence-informed treatment options and recommendations.

The evidence base

We conducted a review of 23 BED studies: 7 medication only, 5 medication plus behavioral, and 11 behavioral only. We focused on studies conducted since September 2005 that included binge frequency, weight, and depression as primary outcomes (see Berkman et al⁶ for a review of BED treatment studies before 2005). The studies included 2,527 participants (2,216 women and 311 men). Although the sex distribution of BED in the general population tends to slightly favor women,² the proportion of women presenting for treatment generally is considerably higher than that of men. In studies that reported on race and/or ethnicity, 1,639 participants were identified as white, 191 as African American, 25 as Hispanic, 2 as Asian, 1 as Native American, and 25 as “other.” Ages ranged from 18 to 77.

Several medications are effective

In placebo-controlled studies, a high-dose selective serotonin reuptake inhibitor (escitalopram⁷), 2 anticonvulsants (zonisamide⁸ and topiramate⁹), a selective norepinephrine reuptake inhibitor (atomoxetine¹⁰), and an appetite suppressant (sibutramine¹¹) were associated with significant decreases in binge eating frequency, weight, and BMI in overweight/obese patients diagnosed with BED (Table 2). In an open-label trial, memantine—a N-methyl-D-aspartate receptor antagonist often used to treat symptoms of Alzheimer’s disease—was associated with a significant reduction in binge eating but no change in weight.¹² Lamotrigine was not significantly different from placebo in reducing binge eating or weight, but showed promise in reducing metabolic parameters such as glucose and triglyceride levels commonly associated with obesity and type 2 diabetes.¹³ Because BED often is comorbid with obesity and type 2 diabetes, lamotrigine augmentation when treating obese individuals with BED warrants further investigation. As with any pharmacologic agent, carefully consider potential side effects and interactions with other drugs before prescribing medications for BED. Informing patients of potential side effects is crucial for patient safety and accuracy of the data collected in well-controlled treatment studies.

Table 2

Pharmacotherapy for binge eating disorder

CBT vs other behavioral approaches

Cognitive-behavioral therapy (CBT), which focuses on identifying and modifying unhealthy thoughts that maintain disordered eating behaviors, is the most widely studied behavioral intervention for BED. Other studied treatments include interpersonal psychotherapy (IPT), motivational interviewing (MI), and structured behavioral weight loss (BWL) (Table 3).^14-24 IPT is a psychodynamically based, time-limited treatment that focuses on the interpersonal context of the disorder and on building interpersonal skills. MI emphasizes exploring and resolving ambivalence about treatment, and works to facilitate change through motivational processes. BWL is centered on making dietary and physical activity changes to achieve weight loss. Behavioral treatments have been delivered in various formats, such as an individual or group setting, by electronic interface, and via self-help approaches. Most studies compared active treatment to a control group, but some compared active treatments head-to-head.

Table 3

CBT and other behavioral interventions for BED

Studies found that CBT and IPT are effective in reducing the frequency of binge eating, whether measured by the number of binge eating episodes or days a patient reports having engaged in binge eating.^14-23 However, some studies suggested that CBT can help a substantial number of patients achieve abstinence from binge eating.^16,20 Adding MI to a self-help approach may improve binge eating outcomes,²⁴ and binge eating can be successfully reduced using individual, group, and CD-ROM delivery formats.²¹ In direct comparisons, individual CBT outperformed group CBT in helping patients recover from BED (ie, no longer meeting diagnostic criteria),¹⁹ and CBT delivered via guided self-help outperformed BWL in helping patients achieve remission.¹⁸

Psychological features of BED typically include low levels of cognitive restraint and high levels of disinhibition, hunger, and shape and weight concerns. Improvements in these psychological measures were observed with CBT,^15-20,22 IPT,²² and MI.²⁴ In direct comparisons, self-help CBT demonstrated greater reductions in perceived hunger and disinhibition than self-help BWL,¹⁸ and individual CBT outperformed group CBT in reducing shape and weight concerns.¹⁹ Isolated studies reported improvements in depression after self-help CBT¹⁸ and MI,²⁴ and sustained improvements²² after group CBT (6 months) and group IPT (12 months). Additional research is needed to determine whether CBT crafted specifically for BED improves self-rated depression or if enhancements targeting depressive symptoms are required.

The impact of behavioral interventions on weight in overweight patients has been mixed. Although some CBT studies reported a substantial decrease in weight,^17,19 others suggested that weight loss among patients treated with CBT is not superior to those in a wait-list control group¹⁶ or is not significant over the course of treatment.^20,21 The impact of BWL on weight outcomes in BED also has been unimpressive: after 12 weeks, self-help BWL was no better than self-help CBT in reducing BMI¹⁸; after 16 weeks, BWL was better than CBT and IPT in achieving clinically significant (≥5%) weight loss, but this advantage was not sustained at 1- and 2-year follow-up.²³ It is difficult to determine why successfully treated BED patients fail to lose weight because one would expect decreases in binge eating to lead to weight loss. It is possible that calories previously consumed during binge eating episodes are distributed over non-binge meals or that patients label binges and non-binge meals differently as a result of treatment.

Combining treatments

BED patients often are treated with a combination of psychotherapy and pharmacotherapy (Table 4).^25-29 When added to CBT, topiramate was associated with improvements in weight and some psychological outcomes,^25,26 but fluoxetine was not.^27,28 Direct comparisons also showed that CBT, alone or combined with fluoxetine, was better than fluoxetine alone in reducing binge eating.²⁷ When combined with an individualized hypocaloric diet, the anti-obesity medication orlistat reduced weight in obese BED patients but had no appreciable effect on binge eating.²⁹ Collectively, the studies we reviewed suggested that combining medication and CBT may improve binge eating and weight loss outcomes; however, additional trials are necessary to determine more definitively which medications combined with CBT are best at producing sustained weight loss while reducing binge eating frequency.

Table 4

Combining medication with behavioral interventions for BED

Recommendations

Evidence suggests that pharmacotherapy and CBT—alone or in combination—are effective in reducing binge eating, and pharmacotherapy is effective in reducing weight in overweight individuals with BED. More research is needed for IPT and MI. It is unclear which medications provide the greatest benefit in terms of binge eating remission; however, pharmacotherapy has a clear advantage in facilitating short-term weight loss. Also, all BED patients should receive medical management to address possible complications such as hypertension or type 2 diabetes. In addition to reducing binge eating, CBT can improve related psychological comorbidities (eg, eating-related psychopathology and depression) and may have additional benefit when combined with pharmacotherapy.

In light of these findings, we recommend augmenting psychotherapeutic care with pharmacotherapy and medical management to address all relevant psychological and medical domains. Future investigations should address the benefits of coordinated psychological and medical care and evaluate how to maintain treatment gains.

Related Resources

• Binge Eating Disorder Association. www.bedaonline.com.
• Brownley KA, Berkman ND, Sedway JA, et al. Binge eating disorder treatment: a systematic review of randomized controlled trials. Int J Eat Disord. 2007;40(4):337-348.

Drug Brand Names

• Atomoxetine • Strattera
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Lamotrigine • Lamictal
• Memantine • Namenda
• Orlistat • Alli, Xenical
• Sertraline • Zoloft
• Sibutramine • Meridia
• Topiramate • Topamax, Topiragen
• Zonisamide • Zonegram

Disclosures

Dr. Peat receives a post-doctoral trainee grant from the National Institutes of Health.

Drs. Brownley, Berkman, and Bulik report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Binge eating is consumption of an unusually large amount of food coupled with a feeling of loss of control over eating. Binge eating disorder (BED) is characterized by recurrent episodes of binge eating without inappropriate compensatory behaviors (eg, self-induced vomiting, misuse of laxatives, diuretics, or other agents, excessive exercise).¹ It is the most common eating disorder in the United States, with a lifetime prevalence of approximately 3.5% in women and 2% in men.² The diagnosis falls within the DSM-IV-TR category of eating disorders not otherwise specified,¹ but clinicians often view it as a distinct clinical phenomenon. In DSM-IV-TR, an individual would meet criteria for BED if he or she engages in regular binge eating behavior in the absence of recurrent compensatory behaviors ≥2 days per week over 6 months.¹ Proposed changes for DSM-5 recognize a distinct BED diagnosis, reduce the frequency criterion to once per week and the duration criterion to the past 3 months, and shift the focus from binge days to binge episodes (Table 1).³

Table 1

Proposed DSM-5 criteria for binge eating disorder

BED can occur in individuals of all body mass indices (BMI), but is common among individuals who are overweight or obese as well as those with depression or type 2 diabetes; BED can complicate treatment of these conditions.^2,4,5 Primary treatment goals are:

• abstinence from binge eating
• improved psychological functioning
• appropriate weight regulation in overweight patients.

We report on 3 approaches to BED treatment: medication only, behavioral intervention only, and medication plus behavioral intervention. This article provides insights about emerging changes in diagnostic criteria for BED as well as evidence-informed treatment options and recommendations.

The evidence base

We conducted a review of 23 BED studies: 7 medication only, 5 medication plus behavioral, and 11 behavioral only. We focused on studies conducted since September 2005 that included binge frequency, weight, and depression as primary outcomes (see Berkman et al⁶ for a review of BED treatment studies before 2005). The studies included 2,527 participants (2,216 women and 311 men). Although the sex distribution of BED in the general population tends to slightly favor women,² the proportion of women presenting for treatment generally is considerably higher than that of men. In studies that reported on race and/or ethnicity, 1,639 participants were identified as white, 191 as African American, 25 as Hispanic, 2 as Asian, 1 as Native American, and 25 as “other.” Ages ranged from 18 to 77.

Several medications are effective

In placebo-controlled studies, a high-dose selective serotonin reuptake inhibitor (escitalopram⁷), 2 anticonvulsants (zonisamide⁸ and topiramate⁹), a selective norepinephrine reuptake inhibitor (atomoxetine¹⁰), and an appetite suppressant (sibutramine¹¹) were associated with significant decreases in binge eating frequency, weight, and BMI in overweight/obese patients diagnosed with BED (Table 2). In an open-label trial, memantine—a N-methyl-D-aspartate receptor antagonist often used to treat symptoms of Alzheimer’s disease—was associated with a significant reduction in binge eating but no change in weight.¹² Lamotrigine was not significantly different from placebo in reducing binge eating or weight, but showed promise in reducing metabolic parameters such as glucose and triglyceride levels commonly associated with obesity and type 2 diabetes.¹³ Because BED often is comorbid with obesity and type 2 diabetes, lamotrigine augmentation when treating obese individuals with BED warrants further investigation. As with any pharmacologic agent, carefully consider potential side effects and interactions with other drugs before prescribing medications for BED. Informing patients of potential side effects is crucial for patient safety and accuracy of the data collected in well-controlled treatment studies.

Table 2

Pharmacotherapy for binge eating disorder

CBT vs other behavioral approaches

Cognitive-behavioral therapy (CBT), which focuses on identifying and modifying unhealthy thoughts that maintain disordered eating behaviors, is the most widely studied behavioral intervention for BED. Other studied treatments include interpersonal psychotherapy (IPT), motivational interviewing (MI), and structured behavioral weight loss (BWL) (Table 3).^14-24 IPT is a psychodynamically based, time-limited treatment that focuses on the interpersonal context of the disorder and on building interpersonal skills. MI emphasizes exploring and resolving ambivalence about treatment, and works to facilitate change through motivational processes. BWL is centered on making dietary and physical activity changes to achieve weight loss. Behavioral treatments have been delivered in various formats, such as an individual or group setting, by electronic interface, and via self-help approaches. Most studies compared active treatment to a control group, but some compared active treatments head-to-head.

Table 3

CBT and other behavioral interventions for BED

Studies found that CBT and IPT are effective in reducing the frequency of binge eating, whether measured by the number of binge eating episodes or days a patient reports having engaged in binge eating.^14-23 However, some studies suggested that CBT can help a substantial number of patients achieve abstinence from binge eating.^16,20 Adding MI to a self-help approach may improve binge eating outcomes,²⁴ and binge eating can be successfully reduced using individual, group, and CD-ROM delivery formats.²¹ In direct comparisons, individual CBT outperformed group CBT in helping patients recover from BED (ie, no longer meeting diagnostic criteria),¹⁹ and CBT delivered via guided self-help outperformed BWL in helping patients achieve remission.¹⁸

Psychological features of BED typically include low levels of cognitive restraint and high levels of disinhibition, hunger, and shape and weight concerns. Improvements in these psychological measures were observed with CBT,^15-20,22 IPT,²² and MI.²⁴ In direct comparisons, self-help CBT demonstrated greater reductions in perceived hunger and disinhibition than self-help BWL,¹⁸ and individual CBT outperformed group CBT in reducing shape and weight concerns.¹⁹ Isolated studies reported improvements in depression after self-help CBT¹⁸ and MI,²⁴ and sustained improvements²² after group CBT (6 months) and group IPT (12 months). Additional research is needed to determine whether CBT crafted specifically for BED improves self-rated depression or if enhancements targeting depressive symptoms are required.

The impact of behavioral interventions on weight in overweight patients has been mixed. Although some CBT studies reported a substantial decrease in weight,^17,19 others suggested that weight loss among patients treated with CBT is not superior to those in a wait-list control group¹⁶ or is not significant over the course of treatment.^20,21 The impact of BWL on weight outcomes in BED also has been unimpressive: after 12 weeks, self-help BWL was no better than self-help CBT in reducing BMI¹⁸; after 16 weeks, BWL was better than CBT and IPT in achieving clinically significant (≥5%) weight loss, but this advantage was not sustained at 1- and 2-year follow-up.²³ It is difficult to determine why successfully treated BED patients fail to lose weight because one would expect decreases in binge eating to lead to weight loss. It is possible that calories previously consumed during binge eating episodes are distributed over non-binge meals or that patients label binges and non-binge meals differently as a result of treatment.

Combining treatments

BED patients often are treated with a combination of psychotherapy and pharmacotherapy (Table 4).^25-29 When added to CBT, topiramate was associated with improvements in weight and some psychological outcomes,^25,26 but fluoxetine was not.^27,28 Direct comparisons also showed that CBT, alone or combined with fluoxetine, was better than fluoxetine alone in reducing binge eating.²⁷ When combined with an individualized hypocaloric diet, the anti-obesity medication orlistat reduced weight in obese BED patients but had no appreciable effect on binge eating.²⁹ Collectively, the studies we reviewed suggested that combining medication and CBT may improve binge eating and weight loss outcomes; however, additional trials are necessary to determine more definitively which medications combined with CBT are best at producing sustained weight loss while reducing binge eating frequency.

Table 4

Combining medication with behavioral interventions for BED

Recommendations

Evidence suggests that pharmacotherapy and CBT—alone or in combination—are effective in reducing binge eating, and pharmacotherapy is effective in reducing weight in overweight individuals with BED. More research is needed for IPT and MI. It is unclear which medications provide the greatest benefit in terms of binge eating remission; however, pharmacotherapy has a clear advantage in facilitating short-term weight loss. Also, all BED patients should receive medical management to address possible complications such as hypertension or type 2 diabetes. In addition to reducing binge eating, CBT can improve related psychological comorbidities (eg, eating-related psychopathology and depression) and may have additional benefit when combined with pharmacotherapy.

In light of these findings, we recommend augmenting psychotherapeutic care with pharmacotherapy and medical management to address all relevant psychological and medical domains. Future investigations should address the benefits of coordinated psychological and medical care and evaluate how to maintain treatment gains.

Related Resources

• Binge Eating Disorder Association. www.bedaonline.com.
• Brownley KA, Berkman ND, Sedway JA, et al. Binge eating disorder treatment: a systematic review of randomized controlled trials. Int J Eat Disord. 2007;40(4):337-348.

Drug Brand Names

• Atomoxetine • Strattera
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Lamotrigine • Lamictal
• Memantine • Namenda
• Orlistat • Alli, Xenical
• Sertraline • Zoloft
• Sibutramine • Meridia
• Topiramate • Topamax, Topiragen
• Zonisamide • Zonegram

Disclosures

Dr. Peat receives a post-doctoral trainee grant from the National Institutes of Health.

Drs. Brownley, Berkman, and Bulik report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at www.facebook.com/CurrentPsychiatry

Mrs. M, age 44, is a married mother of 2 who presents to the psychiatric clinic with increased anxiety that recently has become intolerable, stating “I can’t stop my head.” She has experienced anxiety for “as long as I can remember.” She was a shy, anxious child who worried about her parents’ health. Her anxiety worsened at college, where she first sought care. She was prescribed diazepam as needed. The next semester, she had a depressive episode, treated with imipramine, 75 mg/d, which she tolerated poorly.

Mrs. M has received episodic supportive therapy since college. She has been plagued by bouts of anxiety and worry, with insomnia, tension, and fatigue. She worries about financial, career, family, and safety issues and has a phobia of spiders. Her family and friends often comment about her excessive worry, and it has strained her marriage and career; she was passed over for a promotion in part because of her anxiousness. Mrs. M also has experienced several depressive episodes.

Mrs. M has sought medical care for various non-specific somatic complaints; all laboratory tests were normal. Approximately 10 years ago, Mrs. M’s primary care physician prescribed fluoxetine, 20 mg/d, but Mrs. M stopped taking it after a few days, stating she felt “more anxious and jittery.”

To meet DSM-IV-TR diagnostic criteria for generalized anxiety disorder (GAD), patients must experience anxiety and worry that they find difficult to control. The worry and anxiety occur more days than not for at least 6 months and cause clinically significant distress and impairment (Table 1).¹ These diagnostic criteria are being reevaluated—the DSM-5 Anxiety Work Group has proposed renaming the condition generalized worry disorder, specifying that only 2 domains need to be impacted by worry, shortening the required time frame of impairment from 6 months to 3 months, and including at least 1 behavioral change spawned by excessive worry.² Although provisional, these recommendations suggest DSM-5 will include changes to GAD when it is published in 2013.

Table 1

DSM-IV-TR diagnostic criteria for generalized anxiety disorder

A common, chronic condition

In the United States, the lifetime prevalence of GAD is 5.7%.³ It is twice as common in women. Although GAD can occur at any age, 75% of patients develop it before age 47; the median age is 31.^3,4 Patients who present with GAD later in life have a better prognosis.^3,4

Approximately 90% of GAD patients will meet criteria for another axis I disorder.³ When GAD patients present for treatment, social phobia and panic disorder are the most common comorbid psychiatric disorders. The lifetime prevalence of a mood disorder among GAD patients is 62%, but as few as 6% of GAD patients will meet criteria for a mood disorder at presentation.³ The onset of GAD usually precedes depression.^5,6

Patients with GAD often first seek treatment from their primary care provider.⁷ A useful screening tool is the GAD-7 (Table 2).⁸ This instrument has a specificity of 92% and sensitivity of 76% for GAD for patients who score ≥8.⁷ Although the GAD-7 cannot confirm a GAD diagnosis, it can prompt clinicians to conduct a more structured interview. Because higher scores correlate with more severe symptoms, the GAD-7 can be used to measure progress.

Table 2

Screening for generalized anxiety disorder: The GAD-7

Differential diagnosis

GAD typically has a chronic course with fluctuating symptom severity over the patient’s lifespan. Assess patients who present with anxiety for medical conditions that mimic GAD. These include:

• endocrine (hyperthyroidism), metabolic (electrolyte abnormalities), respiratory (asthma), neurologic (seizure disorder), or cardiac (arrhythmia) conditions
• nutritional deficiencies, especially of B vitamins and folate
• ingestion of substances or medications that may cause anxiety, such as caffeine or amphetamines.

A thorough history, medication review, and physical examination—as well as routine tests such as metabolic panel, complete blood count, thyroid function tests, urine drug screen, and electrocardiography—will capture most of these potential etiologies. In addition to ruling out medical causes, also assess for comorbid psychiatric conditions before reaching a diagnosis.

Evidence-based treatments

The treatment armamentarium for GAD includes psychotherapy and pharmacotherapy; complementary and alternative medicine (CAM) modalities may be useful adjunctive treatments. Which approach to use is determined by clinical judgment and the patient’s symptom severity and preferences. Combination therapy consisting of psychotherapy and medication often is appropriate.

Psychotherapy. Cognitive-behavioral therapy (CBT) is the preferred form of psychotherapy for GAD because it results in sustained improvements for patients with anxiety.^5,9 Other modalities that may be effective include psychodynamic psychotherapy, mindfulness-based therapy, and interpersonal psychotherapy.^10,11

Pharmacotherapy. As few as one-quarter of patients with GAD receive medications at appropriate dose and duration.¹² Antidepressants are a first-line pharmacotherapy.⁵ Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are highly effective for treating GAD.⁵ Paroxetine, escitalopram, duloxetine, and venlafaxine are FDA-approved for GAD, but other SSRIs also are used as primary treatment.⁵ Assuming the selected agent is tolerable and efficacious, a treatment course of 12 months is recommended.¹³

Benzodiazepines promote binding of the neuroinhibitory transmitter γ-aminobutyric acid and enhance chloride ion influx, thus reducing anxiety. Benzodiazepines have been widely used because of their rapid onset of action and effectiveness in managing anxiety, but their role in long-term management of GAD is unclear because these medications increase the risk of addiction, cognitive dulling, memory impairment, psychomotor retardation, and respiratory depression when combined with other CNS depressants such as alcohol and opiates. Before prescribing a benzodiazepine, conduct a thorough risk-benefit analysis and obtain informed consent. Long-term benzodiazepine monotherapy is not recommended.^5,14

Hydroxyzine is an alternative to benzodiazepines.¹⁵ It works as an antihistamine and is FDA-approved for psychogenic neurosis, a Freudian distinction encompassing anxiety derived from psychological rather than physiological factors.

The azapirone buspirone is a nonaddictive, generally non-sedating 5-HT1A agonist. Although anecdotally some psychiatrists may report limited clinical utility, many analyses found azapirones, including buspirone, were effective for GAD,^16,17 particularly for patients with comorbid depression.¹⁸

Tricyclic antidepressants are not a first-line choice because of their side effect profile and potential for drug-drug interactions. Nonetheless, some research suggests imipramine may be a reasonable option for GAD.^14,19

Although not FDA-approved for GAD, anticonvulsant and antipsychotic medications may be reasonable adjunctive agents for patients with refractory GAD. Studies have suggested gabapentin²⁰ and quetiapine²¹ as options.

Investigational treatments. Glutaminergic transmission is being investigated as a target for pharmacotherapy for GAD. In an 8-week, open-label trial, 12 of 15 GAD patients responded to the antiglutamatergic agent riluzole, 100 mg/d, and 8 patients achieved remission.²² In another study, pregabalin, which promotes calcium channel blockade, significantly reduced patients’ scores on the Hamilton Anxiety Rating Scale.²³ However, this medication is a schedule V controlled substance and little is known about its long-term effects. Researchers had proposed that inhibition of corticotropin-releasing factor (CRF) may help reduce anxiety, but in a double-blind, placebo-controlled trial, they found that the CRF antagonist pexacerfont was no more effective than placebo.²⁴

CAM treatments. A meta-analysis found that compared with placebo, kava extract (Piper methysticum) effectively reduced anxiety symptoms.²⁵ However, considering its risk for hepatotoxicity, kava is not a recommended treatment.²⁶ Although valerian, St. John’s wort, and passionflower have been used to manage GAD, there is insufficient evidence of their effectiveness and safety.²⁶ No strong evidence supports nutritional supplements such as ginger, amino acids, and omega-3 fatty acids (fish oils) as treatment for GAD. Although there’s limited research on resistance training, aromatherapy, yoga, meditation, or acupuncture for treating anxiety, consider these treatments if your patient finds them helpful, because generally they are not contraindicated.

CASE CONTINUED: An antidepressant and CBT

Mrs. M reluctantly agrees to a trial of sertraline, 50 mg/d. She refuses a prescription for clonazepam because she is afraid of drug dependence but accepts a referral for CBT. Two days later, she calls the clinic and says she is more anxious and wants to stop the sertraline. The psychiatrist reassures her and reduces the dosage to 25 mg/d.

Mrs. M’s spike of anxiety resolves by her 2-week follow-up appointment and sertraline is titrated to 200 mg/d. Her irritability, anxiety, and mood improve within 2 months. The worry does not completely resolve, but she is much improved at 6 months, and the focus of her therapy shifts to her marriage.

Related Resources

• Goldberg D, Kendler KS, Sirvatka PJ, et al, eds. Diagnostic issues in depression and generalized anxiety disorder—refining the research agenda for DSM-V. Arlington, VA: American Psychiatric Publishing; 2010.
• Fricchione G. Generalized anxiety disorder. N Engl J Med. 2004;351(7):675-682.

Drug Brand Names

• Buspirone • Buspar
• Clonazepam •Klonopin
• Diazepam • Valium
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin• Neurontin
• Hydroxyzine • Vistaril, Atarax
• Imipramine • Tofranil
• Paroxetine • Paxil
• Pregabalin • Lyrica
• Quetiapine • Seroquel
• Riluzole • Rilutek
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Barry reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at www.facebook.com/CurrentPsychiatry

Mrs. M, age 44, is a married mother of 2 who presents to the psychiatric clinic with increased anxiety that recently has become intolerable, stating “I can’t stop my head.” She has experienced anxiety for “as long as I can remember.” She was a shy, anxious child who worried about her parents’ health. Her anxiety worsened at college, where she first sought care. She was prescribed diazepam as needed. The next semester, she had a depressive episode, treated with imipramine, 75 mg/d, which she tolerated poorly.

Mrs. M has received episodic supportive therapy since college. She has been plagued by bouts of anxiety and worry, with insomnia, tension, and fatigue. She worries about financial, career, family, and safety issues and has a phobia of spiders. Her family and friends often comment about her excessive worry, and it has strained her marriage and career; she was passed over for a promotion in part because of her anxiousness. Mrs. M also has experienced several depressive episodes.

Mrs. M has sought medical care for various non-specific somatic complaints; all laboratory tests were normal. Approximately 10 years ago, Mrs. M’s primary care physician prescribed fluoxetine, 20 mg/d, but Mrs. M stopped taking it after a few days, stating she felt “more anxious and jittery.”

To meet DSM-IV-TR diagnostic criteria for generalized anxiety disorder (GAD), patients must experience anxiety and worry that they find difficult to control. The worry and anxiety occur more days than not for at least 6 months and cause clinically significant distress and impairment (Table 1).¹ These diagnostic criteria are being reevaluated—the DSM-5 Anxiety Work Group has proposed renaming the condition generalized worry disorder, specifying that only 2 domains need to be impacted by worry, shortening the required time frame of impairment from 6 months to 3 months, and including at least 1 behavioral change spawned by excessive worry.² Although provisional, these recommendations suggest DSM-5 will include changes to GAD when it is published in 2013.

Table 1

DSM-IV-TR diagnostic criteria for generalized anxiety disorder

A common, chronic condition

In the United States, the lifetime prevalence of GAD is 5.7%.³ It is twice as common in women. Although GAD can occur at any age, 75% of patients develop it before age 47; the median age is 31.^3,4 Patients who present with GAD later in life have a better prognosis.^3,4

Approximately 90% of GAD patients will meet criteria for another axis I disorder.³ When GAD patients present for treatment, social phobia and panic disorder are the most common comorbid psychiatric disorders. The lifetime prevalence of a mood disorder among GAD patients is 62%, but as few as 6% of GAD patients will meet criteria for a mood disorder at presentation.³ The onset of GAD usually precedes depression.^5,6

Patients with GAD often first seek treatment from their primary care provider.⁷ A useful screening tool is the GAD-7 (Table 2).⁸ This instrument has a specificity of 92% and sensitivity of 76% for GAD for patients who score ≥8.⁷ Although the GAD-7 cannot confirm a GAD diagnosis, it can prompt clinicians to conduct a more structured interview. Because higher scores correlate with more severe symptoms, the GAD-7 can be used to measure progress.

Table 2

Screening for generalized anxiety disorder: The GAD-7

Differential diagnosis

GAD typically has a chronic course with fluctuating symptom severity over the patient’s lifespan. Assess patients who present with anxiety for medical conditions that mimic GAD. These include:

• endocrine (hyperthyroidism), metabolic (electrolyte abnormalities), respiratory (asthma), neurologic (seizure disorder), or cardiac (arrhythmia) conditions
• nutritional deficiencies, especially of B vitamins and folate
• ingestion of substances or medications that may cause anxiety, such as caffeine or amphetamines.

A thorough history, medication review, and physical examination—as well as routine tests such as metabolic panel, complete blood count, thyroid function tests, urine drug screen, and electrocardiography—will capture most of these potential etiologies. In addition to ruling out medical causes, also assess for comorbid psychiatric conditions before reaching a diagnosis.

Evidence-based treatments

The treatment armamentarium for GAD includes psychotherapy and pharmacotherapy; complementary and alternative medicine (CAM) modalities may be useful adjunctive treatments. Which approach to use is determined by clinical judgment and the patient’s symptom severity and preferences. Combination therapy consisting of psychotherapy and medication often is appropriate.

Psychotherapy. Cognitive-behavioral therapy (CBT) is the preferred form of psychotherapy for GAD because it results in sustained improvements for patients with anxiety.^5,9 Other modalities that may be effective include psychodynamic psychotherapy, mindfulness-based therapy, and interpersonal psychotherapy.^10,11

Pharmacotherapy. As few as one-quarter of patients with GAD receive medications at appropriate dose and duration.¹² Antidepressants are a first-line pharmacotherapy.⁵ Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are highly effective for treating GAD.⁵ Paroxetine, escitalopram, duloxetine, and venlafaxine are FDA-approved for GAD, but other SSRIs also are used as primary treatment.⁵ Assuming the selected agent is tolerable and efficacious, a treatment course of 12 months is recommended.¹³

Benzodiazepines promote binding of the neuroinhibitory transmitter γ-aminobutyric acid and enhance chloride ion influx, thus reducing anxiety. Benzodiazepines have been widely used because of their rapid onset of action and effectiveness in managing anxiety, but their role in long-term management of GAD is unclear because these medications increase the risk of addiction, cognitive dulling, memory impairment, psychomotor retardation, and respiratory depression when combined with other CNS depressants such as alcohol and opiates. Before prescribing a benzodiazepine, conduct a thorough risk-benefit analysis and obtain informed consent. Long-term benzodiazepine monotherapy is not recommended.^5,14

Hydroxyzine is an alternative to benzodiazepines.¹⁵ It works as an antihistamine and is FDA-approved for psychogenic neurosis, a Freudian distinction encompassing anxiety derived from psychological rather than physiological factors.

The azapirone buspirone is a nonaddictive, generally non-sedating 5-HT1A agonist. Although anecdotally some psychiatrists may report limited clinical utility, many analyses found azapirones, including buspirone, were effective for GAD,^16,17 particularly for patients with comorbid depression.¹⁸

Tricyclic antidepressants are not a first-line choice because of their side effect profile and potential for drug-drug interactions. Nonetheless, some research suggests imipramine may be a reasonable option for GAD.^14,19

Although not FDA-approved for GAD, anticonvulsant and antipsychotic medications may be reasonable adjunctive agents for patients with refractory GAD. Studies have suggested gabapentin²⁰ and quetiapine²¹ as options.

Investigational treatments. Glutaminergic transmission is being investigated as a target for pharmacotherapy for GAD. In an 8-week, open-label trial, 12 of 15 GAD patients responded to the antiglutamatergic agent riluzole, 100 mg/d, and 8 patients achieved remission.²² In another study, pregabalin, which promotes calcium channel blockade, significantly reduced patients’ scores on the Hamilton Anxiety Rating Scale.²³ However, this medication is a schedule V controlled substance and little is known about its long-term effects. Researchers had proposed that inhibition of corticotropin-releasing factor (CRF) may help reduce anxiety, but in a double-blind, placebo-controlled trial, they found that the CRF antagonist pexacerfont was no more effective than placebo.²⁴

CAM treatments. A meta-analysis found that compared with placebo, kava extract (Piper methysticum) effectively reduced anxiety symptoms.²⁵ However, considering its risk for hepatotoxicity, kava is not a recommended treatment.²⁶ Although valerian, St. John’s wort, and passionflower have been used to manage GAD, there is insufficient evidence of their effectiveness and safety.²⁶ No strong evidence supports nutritional supplements such as ginger, amino acids, and omega-3 fatty acids (fish oils) as treatment for GAD. Although there’s limited research on resistance training, aromatherapy, yoga, meditation, or acupuncture for treating anxiety, consider these treatments if your patient finds them helpful, because generally they are not contraindicated.

CASE CONTINUED: An antidepressant and CBT

Mrs. M reluctantly agrees to a trial of sertraline, 50 mg/d. She refuses a prescription for clonazepam because she is afraid of drug dependence but accepts a referral for CBT. Two days later, she calls the clinic and says she is more anxious and wants to stop the sertraline. The psychiatrist reassures her and reduces the dosage to 25 mg/d.

Mrs. M’s spike of anxiety resolves by her 2-week follow-up appointment and sertraline is titrated to 200 mg/d. Her irritability, anxiety, and mood improve within 2 months. The worry does not completely resolve, but she is much improved at 6 months, and the focus of her therapy shifts to her marriage.

Related Resources

• Goldberg D, Kendler KS, Sirvatka PJ, et al, eds. Diagnostic issues in depression and generalized anxiety disorder—refining the research agenda for DSM-V. Arlington, VA: American Psychiatric Publishing; 2010.
• Fricchione G. Generalized anxiety disorder. N Engl J Med. 2004;351(7):675-682.

Drug Brand Names

• Buspirone • Buspar
• Clonazepam •Klonopin
• Diazepam • Valium
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin• Neurontin
• Hydroxyzine • Vistaril, Atarax
• Imipramine • Tofranil
• Paroxetine • Paxil
• Pregabalin • Lyrica
• Quetiapine • Seroquel
• Riluzole • Rilutek
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Barry reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at www.facebook.com/CurrentPsychiatry

Mrs. M, age 44, is a married mother of 2 who presents to the psychiatric clinic with increased anxiety that recently has become intolerable, stating “I can’t stop my head.” She has experienced anxiety for “as long as I can remember.” She was a shy, anxious child who worried about her parents’ health. Her anxiety worsened at college, where she first sought care. She was prescribed diazepam as needed. The next semester, she had a depressive episode, treated with imipramine, 75 mg/d, which she tolerated poorly.

Mrs. M has received episodic supportive therapy since college. She has been plagued by bouts of anxiety and worry, with insomnia, tension, and fatigue. She worries about financial, career, family, and safety issues and has a phobia of spiders. Her family and friends often comment about her excessive worry, and it has strained her marriage and career; she was passed over for a promotion in part because of her anxiousness. Mrs. M also has experienced several depressive episodes.

Mrs. M has sought medical care for various non-specific somatic complaints; all laboratory tests were normal. Approximately 10 years ago, Mrs. M’s primary care physician prescribed fluoxetine, 20 mg/d, but Mrs. M stopped taking it after a few days, stating she felt “more anxious and jittery.”

To meet DSM-IV-TR diagnostic criteria for generalized anxiety disorder (GAD), patients must experience anxiety and worry that they find difficult to control. The worry and anxiety occur more days than not for at least 6 months and cause clinically significant distress and impairment (Table 1).¹ These diagnostic criteria are being reevaluated—the DSM-5 Anxiety Work Group has proposed renaming the condition generalized worry disorder, specifying that only 2 domains need to be impacted by worry, shortening the required time frame of impairment from 6 months to 3 months, and including at least 1 behavioral change spawned by excessive worry.² Although provisional, these recommendations suggest DSM-5 will include changes to GAD when it is published in 2013.

Table 1

DSM-IV-TR diagnostic criteria for generalized anxiety disorder

A common, chronic condition

In the United States, the lifetime prevalence of GAD is 5.7%.³ It is twice as common in women. Although GAD can occur at any age, 75% of patients develop it before age 47; the median age is 31.^3,4 Patients who present with GAD later in life have a better prognosis.^3,4

Approximately 90% of GAD patients will meet criteria for another axis I disorder.³ When GAD patients present for treatment, social phobia and panic disorder are the most common comorbid psychiatric disorders. The lifetime prevalence of a mood disorder among GAD patients is 62%, but as few as 6% of GAD patients will meet criteria for a mood disorder at presentation.³ The onset of GAD usually precedes depression.^5,6

Patients with GAD often first seek treatment from their primary care provider.⁷ A useful screening tool is the GAD-7 (Table 2).⁸ This instrument has a specificity of 92% and sensitivity of 76% for GAD for patients who score ≥8.⁷ Although the GAD-7 cannot confirm a GAD diagnosis, it can prompt clinicians to conduct a more structured interview. Because higher scores correlate with more severe symptoms, the GAD-7 can be used to measure progress.

Table 2

Screening for generalized anxiety disorder: The GAD-7

Differential diagnosis

GAD typically has a chronic course with fluctuating symptom severity over the patient’s lifespan. Assess patients who present with anxiety for medical conditions that mimic GAD. These include:

• endocrine (hyperthyroidism), metabolic (electrolyte abnormalities), respiratory (asthma), neurologic (seizure disorder), or cardiac (arrhythmia) conditions
• nutritional deficiencies, especially of B vitamins and folate
• ingestion of substances or medications that may cause anxiety, such as caffeine or amphetamines.

A thorough history, medication review, and physical examination—as well as routine tests such as metabolic panel, complete blood count, thyroid function tests, urine drug screen, and electrocardiography—will capture most of these potential etiologies. In addition to ruling out medical causes, also assess for comorbid psychiatric conditions before reaching a diagnosis.

Evidence-based treatments

The treatment armamentarium for GAD includes psychotherapy and pharmacotherapy; complementary and alternative medicine (CAM) modalities may be useful adjunctive treatments. Which approach to use is determined by clinical judgment and the patient’s symptom severity and preferences. Combination therapy consisting of psychotherapy and medication often is appropriate.

Psychotherapy. Cognitive-behavioral therapy (CBT) is the preferred form of psychotherapy for GAD because it results in sustained improvements for patients with anxiety.^5,9 Other modalities that may be effective include psychodynamic psychotherapy, mindfulness-based therapy, and interpersonal psychotherapy.^10,11

Pharmacotherapy. As few as one-quarter of patients with GAD receive medications at appropriate dose and duration.¹² Antidepressants are a first-line pharmacotherapy.⁵ Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are highly effective for treating GAD.⁵ Paroxetine, escitalopram, duloxetine, and venlafaxine are FDA-approved for GAD, but other SSRIs also are used as primary treatment.⁵ Assuming the selected agent is tolerable and efficacious, a treatment course of 12 months is recommended.¹³

Benzodiazepines promote binding of the neuroinhibitory transmitter γ-aminobutyric acid and enhance chloride ion influx, thus reducing anxiety. Benzodiazepines have been widely used because of their rapid onset of action and effectiveness in managing anxiety, but their role in long-term management of GAD is unclear because these medications increase the risk of addiction, cognitive dulling, memory impairment, psychomotor retardation, and respiratory depression when combined with other CNS depressants such as alcohol and opiates. Before prescribing a benzodiazepine, conduct a thorough risk-benefit analysis and obtain informed consent. Long-term benzodiazepine monotherapy is not recommended.^5,14

Hydroxyzine is an alternative to benzodiazepines.¹⁵ It works as an antihistamine and is FDA-approved for psychogenic neurosis, a Freudian distinction encompassing anxiety derived from psychological rather than physiological factors.

The azapirone buspirone is a nonaddictive, generally non-sedating 5-HT1A agonist. Although anecdotally some psychiatrists may report limited clinical utility, many analyses found azapirones, including buspirone, were effective for GAD,^16,17 particularly for patients with comorbid depression.¹⁸

Tricyclic antidepressants are not a first-line choice because of their side effect profile and potential for drug-drug interactions. Nonetheless, some research suggests imipramine may be a reasonable option for GAD.^14,19

Although not FDA-approved for GAD, anticonvulsant and antipsychotic medications may be reasonable adjunctive agents for patients with refractory GAD. Studies have suggested gabapentin²⁰ and quetiapine²¹ as options.

Investigational treatments. Glutaminergic transmission is being investigated as a target for pharmacotherapy for GAD. In an 8-week, open-label trial, 12 of 15 GAD patients responded to the antiglutamatergic agent riluzole, 100 mg/d, and 8 patients achieved remission.²² In another study, pregabalin, which promotes calcium channel blockade, significantly reduced patients’ scores on the Hamilton Anxiety Rating Scale.²³ However, this medication is a schedule V controlled substance and little is known about its long-term effects. Researchers had proposed that inhibition of corticotropin-releasing factor (CRF) may help reduce anxiety, but in a double-blind, placebo-controlled trial, they found that the CRF antagonist pexacerfont was no more effective than placebo.²⁴

CAM treatments. A meta-analysis found that compared with placebo, kava extract (Piper methysticum) effectively reduced anxiety symptoms.²⁵ However, considering its risk for hepatotoxicity, kava is not a recommended treatment.²⁶ Although valerian, St. John’s wort, and passionflower have been used to manage GAD, there is insufficient evidence of their effectiveness and safety.²⁶ No strong evidence supports nutritional supplements such as ginger, amino acids, and omega-3 fatty acids (fish oils) as treatment for GAD. Although there’s limited research on resistance training, aromatherapy, yoga, meditation, or acupuncture for treating anxiety, consider these treatments if your patient finds them helpful, because generally they are not contraindicated.

CASE CONTINUED: An antidepressant and CBT

Mrs. M reluctantly agrees to a trial of sertraline, 50 mg/d. She refuses a prescription for clonazepam because she is afraid of drug dependence but accepts a referral for CBT. Two days later, she calls the clinic and says she is more anxious and wants to stop the sertraline. The psychiatrist reassures her and reduces the dosage to 25 mg/d.

Mrs. M’s spike of anxiety resolves by her 2-week follow-up appointment and sertraline is titrated to 200 mg/d. Her irritability, anxiety, and mood improve within 2 months. The worry does not completely resolve, but she is much improved at 6 months, and the focus of her therapy shifts to her marriage.

Related Resources

• Goldberg D, Kendler KS, Sirvatka PJ, et al, eds. Diagnostic issues in depression and generalized anxiety disorder—refining the research agenda for DSM-V. Arlington, VA: American Psychiatric Publishing; 2010.
• Fricchione G. Generalized anxiety disorder. N Engl J Med. 2004;351(7):675-682.

Drug Brand Names

• Buspirone • Buspar
• Clonazepam •Klonopin
• Diazepam • Valium
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin• Neurontin
• Hydroxyzine • Vistaril, Atarax
• Imipramine • Tofranil
• Paroxetine • Paxil
• Pregabalin • Lyrica
• Quetiapine • Seroquel
• Riluzole • Rilutek
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Barry reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

The clinical milieu of type 2 diabetes mellitus (T2DM) is undoubtedly one of the most challenging faced by family physicians. The association of T2DM with other chronic diseases, such as hypertension, dyslipidemia, cardiovascular disease, and obesity, speaks to the complex issues that must be addressed. Considering the complexity of these issues, it is important to recognize that, as a chronic disease, T2DM is largely self-managed and patients mostly control their own DM-related health outcomes. To assist patients with T2DM to successfully take on this responsibility, family physicians should raise and discuss the treatment options available to achieve agreed upon goals, and, in consultation with the patient, recommend treatment options that best address the patient’s clinical issues and meet the patient’s needs. These steps are important to help motivate the patient and promote long-term treatment adherence. Among the treatment options available for T2DM, the challenges of self-management are perhaps greatest with insulin.

Insulin is the most physiologic and effective glucose-lowering agent available, and is recommended as glucose-lowering therapy over the spectrum of T2DM.^1,2 Yet studies show that the initiation of insulin treatment is often delayed, sometimes for years, following loss of glycemic control with oral glucose-lowering agents.^3,4 Once initiated, adherence to insulin tends to be moderate at best.^5,6 It is crucial that family physicians address the issues that contribute to low levels of acceptance and adherence to insulin treatment. In addition, physicians need a firm understanding of how to initiate, modify, and intensify insulin therapy. The primary goal of this supplement is to provide the family physician with a detailed understanding of the current recommendations for, and advances in, insulin treatment.

This supplement includes three articles; the first of which is a historical review of the discovery of insulin. Also included in that article, by Michael Heile, MD, and Doron Schneider, MD, FACP, is a review of the evolution of insulin, including a comparison of the clinical pharmacology of human and analog insulins. The second article begins with a discussion of the conceptual strategies to address patient barriers that have a dramatic impact on the acceptance of, and self-management with, insulin. Building on that foundation, Luigi Meneghini, MD, MBA, and Timothy Reid, MD, present 4 case studies that detail how to assist patients in the implementation of these strategies when initiating or intensifying insulin therapy. The case studies also provide practical considerations with respect to dosing basal, basal-bolus, and premixed insulin. The third article examines advances in insulin, with a focus on the investigational agent, ultra–long-acting insulin degludec. Allen King, MD, provides a solid foundation of the clinical pharmacology of insulin degludec and the clinical experience to date regarding the use of insulin degludec in patients with type 1 DM or T2DM.

It is hoped that the information in this supplement will prove helpful for the practicing family physician in managing patients with this increasingly common disease and its associated clinical dilemmas.

The clinical milieu of type 2 diabetes mellitus (T2DM) is undoubtedly one of the most challenging faced by family physicians. The association of T2DM with other chronic diseases, such as hypertension, dyslipidemia, cardiovascular disease, and obesity, speaks to the complex issues that must be addressed. Considering the complexity of these issues, it is important to recognize that, as a chronic disease, T2DM is largely self-managed and patients mostly control their own DM-related health outcomes. To assist patients with T2DM to successfully take on this responsibility, family physicians should raise and discuss the treatment options available to achieve agreed upon goals, and, in consultation with the patient, recommend treatment options that best address the patient’s clinical issues and meet the patient’s needs. These steps are important to help motivate the patient and promote long-term treatment adherence. Among the treatment options available for T2DM, the challenges of self-management are perhaps greatest with insulin.

Insulin is the most physiologic and effective glucose-lowering agent available, and is recommended as glucose-lowering therapy over the spectrum of T2DM.^1,2 Yet studies show that the initiation of insulin treatment is often delayed, sometimes for years, following loss of glycemic control with oral glucose-lowering agents.^3,4 Once initiated, adherence to insulin tends to be moderate at best.^5,6 It is crucial that family physicians address the issues that contribute to low levels of acceptance and adherence to insulin treatment. In addition, physicians need a firm understanding of how to initiate, modify, and intensify insulin therapy. The primary goal of this supplement is to provide the family physician with a detailed understanding of the current recommendations for, and advances in, insulin treatment.

This supplement includes three articles; the first of which is a historical review of the discovery of insulin. Also included in that article, by Michael Heile, MD, and Doron Schneider, MD, FACP, is a review of the evolution of insulin, including a comparison of the clinical pharmacology of human and analog insulins. The second article begins with a discussion of the conceptual strategies to address patient barriers that have a dramatic impact on the acceptance of, and self-management with, insulin. Building on that foundation, Luigi Meneghini, MD, MBA, and Timothy Reid, MD, present 4 case studies that detail how to assist patients in the implementation of these strategies when initiating or intensifying insulin therapy. The case studies also provide practical considerations with respect to dosing basal, basal-bolus, and premixed insulin. The third article examines advances in insulin, with a focus on the investigational agent, ultra–long-acting insulin degludec. Allen King, MD, provides a solid foundation of the clinical pharmacology of insulin degludec and the clinical experience to date regarding the use of insulin degludec in patients with type 1 DM or T2DM.

It is hoped that the information in this supplement will prove helpful for the practicing family physician in managing patients with this increasingly common disease and its associated clinical dilemmas.

The clinical milieu of type 2 diabetes mellitus (T2DM) is undoubtedly one of the most challenging faced by family physicians. The association of T2DM with other chronic diseases, such as hypertension, dyslipidemia, cardiovascular disease, and obesity, speaks to the complex issues that must be addressed. Considering the complexity of these issues, it is important to recognize that, as a chronic disease, T2DM is largely self-managed and patients mostly control their own DM-related health outcomes. To assist patients with T2DM to successfully take on this responsibility, family physicians should raise and discuss the treatment options available to achieve agreed upon goals, and, in consultation with the patient, recommend treatment options that best address the patient’s clinical issues and meet the patient’s needs. These steps are important to help motivate the patient and promote long-term treatment adherence. Among the treatment options available for T2DM, the challenges of self-management are perhaps greatest with insulin.

Insulin is the most physiologic and effective glucose-lowering agent available, and is recommended as glucose-lowering therapy over the spectrum of T2DM.^1,2 Yet studies show that the initiation of insulin treatment is often delayed, sometimes for years, following loss of glycemic control with oral glucose-lowering agents.^3,4 Once initiated, adherence to insulin tends to be moderate at best.^5,6 It is crucial that family physicians address the issues that contribute to low levels of acceptance and adherence to insulin treatment. In addition, physicians need a firm understanding of how to initiate, modify, and intensify insulin therapy. The primary goal of this supplement is to provide the family physician with a detailed understanding of the current recommendations for, and advances in, insulin treatment.

This supplement includes three articles; the first of which is a historical review of the discovery of insulin. Also included in that article, by Michael Heile, MD, and Doron Schneider, MD, FACP, is a review of the evolution of insulin, including a comparison of the clinical pharmacology of human and analog insulins. The second article begins with a discussion of the conceptual strategies to address patient barriers that have a dramatic impact on the acceptance of, and self-management with, insulin. Building on that foundation, Luigi Meneghini, MD, MBA, and Timothy Reid, MD, present 4 case studies that detail how to assist patients in the implementation of these strategies when initiating or intensifying insulin therapy. The case studies also provide practical considerations with respect to dosing basal, basal-bolus, and premixed insulin. The third article examines advances in insulin, with a focus on the investigational agent, ultra–long-acting insulin degludec. Allen King, MD, provides a solid foundation of the clinical pharmacology of insulin degludec and the clinical experience to date regarding the use of insulin degludec in patients with type 1 DM or T2DM.

It is hoped that the information in this supplement will prove helpful for the practicing family physician in managing patients with this increasingly common disease and its associated clinical dilemmas.

The clinical milieu of type 2 diabetes mellitus (T2DM) is undoubtedly one of the most challenging faced by family physicians. The association of T2DM with other chronic diseases, such as hypertension, dyslipidemia, cardiovascular disease, and obesity, speaks to the complex issues that must be addressed. Considering the complexity of these issues, it is important to recognize that, as a chronic disease, T2DM is largely self-managed and patients mostly control their own DM-related health outcomes. To assist patients with T2DM to successfully take on this responsibility, family physicians should raise and discuss the treatment options available to achieve agreed upon goals, and, in consultation with the patient, recommend treatment options that best address the patient’s clinical issues and meet the patient’s needs. These steps are important to help motivate the patient and promote long-term treatment adherence. Among the treatment options available for T2DM, the challenges of self-management are perhaps greatest with insulin.

Insulin is the most physiologic and effective glucose-lowering agent available, and is recommended as glucose-lowering therapy over the spectrum of T2DM.^1,2 Yet studies show that the initiation of insulin treatment is often delayed, sometimes for years, following loss of glycemic control with oral glucose-lowering agents.^3,4 Once initiated, adherence to insulin tends to be moderate at best.^5,6 It is crucial that family physicians address the issues that contribute to low levels of acceptance and adherence to insulin treatment. In addition, physicians need a firm understanding of how to initiate, modify, and intensify insulin therapy. The primary goal of this supplement is to provide the family physician with a detailed understanding of the current recommendations for, and advances in, insulin treatment.

This supplement includes three articles; the first of which is a historical review of the discovery of insulin. Also included in that article, by Michael Heile, MD, and Doron Schneider, MD, FACP, is a review of the evolution of insulin, including a comparison of the clinical pharmacology of human and analog insulins. The second article begins with a discussion of the conceptual strategies to address patient barriers that have a dramatic impact on the acceptance of, and self-management with, insulin. Building on that foundation, Luigi Meneghini, MD, MBA, and Timothy Reid, MD, present 4 case studies that detail how to assist patients in the implementation of these strategies when initiating or intensifying insulin therapy. The case studies also provide practical considerations with respect to dosing basal, basal-bolus, and premixed insulin. The third article examines advances in insulin, with a focus on the investigational agent, ultra–long-acting insulin degludec. Allen King, MD, provides a solid foundation of the clinical pharmacology of insulin degludec and the clinical experience to date regarding the use of insulin degludec in patients with type 1 DM or T2DM.

It is hoped that the information in this supplement will prove helpful for the practicing family physician in managing patients with this increasingly common disease and its associated clinical dilemmas.

The clinical milieu of type 2 diabetes mellitus (T2DM) is undoubtedly one of the most challenging faced by family physicians. The association of T2DM with other chronic diseases, such as hypertension, dyslipidemia, cardiovascular disease, and obesity, speaks to the complex issues that must be addressed. Considering the complexity of these issues, it is important to recognize that, as a chronic disease, T2DM is largely self-managed and patients mostly control their own DM-related health outcomes. To assist patients with T2DM to successfully take on this responsibility, family physicians should raise and discuss the treatment options available to achieve agreed upon goals, and, in consultation with the patient, recommend treatment options that best address the patient’s clinical issues and meet the patient’s needs. These steps are important to help motivate the patient and promote long-term treatment adherence. Among the treatment options available for T2DM, the challenges of self-management are perhaps greatest with insulin.

Insulin is the most physiologic and effective glucose-lowering agent available, and is recommended as glucose-lowering therapy over the spectrum of T2DM.^1,2 Yet studies show that the initiation of insulin treatment is often delayed, sometimes for years, following loss of glycemic control with oral glucose-lowering agents.^3,4 Once initiated, adherence to insulin tends to be moderate at best.^5,6 It is crucial that family physicians address the issues that contribute to low levels of acceptance and adherence to insulin treatment. In addition, physicians need a firm understanding of how to initiate, modify, and intensify insulin therapy. The primary goal of this supplement is to provide the family physician with a detailed understanding of the current recommendations for, and advances in, insulin treatment.

This supplement includes three articles; the first of which is a historical review of the discovery of insulin. Also included in that article, by Michael Heile, MD, and Doron Schneider, MD, FACP, is a review of the evolution of insulin, including a comparison of the clinical pharmacology of human and analog insulins. The second article begins with a discussion of the conceptual strategies to address patient barriers that have a dramatic impact on the acceptance of, and self-management with, insulin. Building on that foundation, Luigi Meneghini, MD, MBA, and Timothy Reid, MD, present 4 case studies that detail how to assist patients in the implementation of these strategies when initiating or intensifying insulin therapy. The case studies also provide practical considerations with respect to dosing basal, basal-bolus, and premixed insulin. The third article examines advances in insulin, with a focus on the investigational agent, ultra–long-acting insulin degludec. Allen King, MD, provides a solid foundation of the clinical pharmacology of insulin degludec and the clinical experience to date regarding the use of insulin degludec in patients with type 1 DM or T2DM.

It is hoped that the information in this supplement will prove helpful for the practicing family physician in managing patients with this increasingly common disease and its associated clinical dilemmas.

The clinical milieu of type 2 diabetes mellitus (T2DM) is undoubtedly one of the most challenging faced by family physicians. The association of T2DM with other chronic diseases, such as hypertension, dyslipidemia, cardiovascular disease, and obesity, speaks to the complex issues that must be addressed. Considering the complexity of these issues, it is important to recognize that, as a chronic disease, T2DM is largely self-managed and patients mostly control their own DM-related health outcomes. To assist patients with T2DM to successfully take on this responsibility, family physicians should raise and discuss the treatment options available to achieve agreed upon goals, and, in consultation with the patient, recommend treatment options that best address the patient’s clinical issues and meet the patient’s needs. These steps are important to help motivate the patient and promote long-term treatment adherence. Among the treatment options available for T2DM, the challenges of self-management are perhaps greatest with insulin.

Insulin is the most physiologic and effective glucose-lowering agent available, and is recommended as glucose-lowering therapy over the spectrum of T2DM.^1,2 Yet studies show that the initiation of insulin treatment is often delayed, sometimes for years, following loss of glycemic control with oral glucose-lowering agents.^3,4 Once initiated, adherence to insulin tends to be moderate at best.^5,6 It is crucial that family physicians address the issues that contribute to low levels of acceptance and adherence to insulin treatment. In addition, physicians need a firm understanding of how to initiate, modify, and intensify insulin therapy. The primary goal of this supplement is to provide the family physician with a detailed understanding of the current recommendations for, and advances in, insulin treatment.

This supplement includes three articles; the first of which is a historical review of the discovery of insulin. Also included in that article, by Michael Heile, MD, and Doron Schneider, MD, FACP, is a review of the evolution of insulin, including a comparison of the clinical pharmacology of human and analog insulins. The second article begins with a discussion of the conceptual strategies to address patient barriers that have a dramatic impact on the acceptance of, and self-management with, insulin. Building on that foundation, Luigi Meneghini, MD, MBA, and Timothy Reid, MD, present 4 case studies that detail how to assist patients in the implementation of these strategies when initiating or intensifying insulin therapy. The case studies also provide practical considerations with respect to dosing basal, basal-bolus, and premixed insulin. The third article examines advances in insulin, with a focus on the investigational agent, ultra–long-acting insulin degludec. Allen King, MD, provides a solid foundation of the clinical pharmacology of insulin degludec and the clinical experience to date regarding the use of insulin degludec in patients with type 1 DM or T2DM.

It is hoped that the information in this supplement will prove helpful for the practicing family physician in managing patients with this increasingly common disease and its associated clinical dilemmas.

A report from the Institute of Medicine in 2005¹ marked a watershed in the thinking about cancer patients and their long-term needs as survivors when it argued for oncology programs in the United States to address the unmet needs of cancer survivors at the community practice level. Cancer care in the United States has tended to focus on the more immediate aspects of the active treatment, limiting our long-term concerns for the patient’s well-being. Indeed, as a community oncologist in the early part of my career,² decades ago, I considered cancer patients “finished” with their cancer and back to “normal” soon after their last acute toxicity ended.² These days, our profession as well as patients and society as a whole have come to understand that the needs of cancer patients continue into well into survivorship, which can span years or even decades. These concerns should be addressed and accommodated through comprehensive, community-based survivorship programs.

*For a PDF of the full article, click on the link to the left of this introduction.

A report from the Institute of Medicine in 2005¹ marked a watershed in the thinking about cancer patients and their long-term needs as survivors when it argued for oncology programs in the United States to address the unmet needs of cancer survivors at the community practice level. Cancer care in the United States has tended to focus on the more immediate aspects of the active treatment, limiting our long-term concerns for the patient’s well-being. Indeed, as a community oncologist in the early part of my career,² decades ago, I considered cancer patients “finished” with their cancer and back to “normal” soon after their last acute toxicity ended.² These days, our profession as well as patients and society as a whole have come to understand that the needs of cancer patients continue into well into survivorship, which can span years or even decades. These concerns should be addressed and accommodated through comprehensive, community-based survivorship programs.

*For a PDF of the full article, click on the link to the left of this introduction.

A report from the Institute of Medicine in 2005¹ marked a watershed in the thinking about cancer patients and their long-term needs as survivors when it argued for oncology programs in the United States to address the unmet needs of cancer survivors at the community practice level. Cancer care in the United States has tended to focus on the more immediate aspects of the active treatment, limiting our long-term concerns for the patient’s well-being. Indeed, as a community oncologist in the early part of my career,² decades ago, I considered cancer patients “finished” with their cancer and back to “normal” soon after their last acute toxicity ended.² These days, our profession as well as patients and society as a whole have come to understand that the needs of cancer patients continue into well into survivorship, which can span years or even decades. These concerns should be addressed and accommodated through comprehensive, community-based survivorship programs.

*For a PDF of the full article, click on the link to the left of this introduction.

With related Commentary

Erwinia chrysanthemi, an asparaginase derived from the bacterium E chrysanthemi, was recently approved by the Food and Drug Administration as a component of multiagent chemotherapy in patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to Escherichia coli (E coli)-derived asparaginase and pegaspargase.¹ Hypersensitivity to E coli-derived asparaginase may occur in up to 30% of patients² with ALL, a common childhood cancer. Leukemic cells are not able to synthesize the amino acid asparagine, which is required for protein metabolism and survival, because of a lack of asparagine synthetase activity. Erwinia-derived asparaginase reduces circulating levels of asparagine by catalyzing the deamidation of asparagine to aspartic acid and ammonia. The reduction of circulating asparagine results in cytotoxicity specific for leukemic cells by depriving them of their source of the amino acid.

*For PDFs of the full report and accompanying Commentary, click on the links to the left of this introduction.

With related Commentary

Erwinia chrysanthemi, an asparaginase derived from the bacterium E chrysanthemi, was recently approved by the Food and Drug Administration as a component of multiagent chemotherapy in patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to Escherichia coli (E coli)-derived asparaginase and pegaspargase.¹ Hypersensitivity to E coli-derived asparaginase may occur in up to 30% of patients² with ALL, a common childhood cancer. Leukemic cells are not able to synthesize the amino acid asparagine, which is required for protein metabolism and survival, because of a lack of asparagine synthetase activity. Erwinia-derived asparaginase reduces circulating levels of asparagine by catalyzing the deamidation of asparagine to aspartic acid and ammonia. The reduction of circulating asparagine results in cytotoxicity specific for leukemic cells by depriving them of their source of the amino acid.

*For PDFs of the full report and accompanying Commentary, click on the links to the left of this introduction.

With related Commentary

Erwinia chrysanthemi, an asparaginase derived from the bacterium E chrysanthemi, was recently approved by the Food and Drug Administration as a component of multiagent chemotherapy in patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to Escherichia coli (E coli)-derived asparaginase and pegaspargase.¹ Hypersensitivity to E coli-derived asparaginase may occur in up to 30% of patients² with ALL, a common childhood cancer. Leukemic cells are not able to synthesize the amino acid asparagine, which is required for protein metabolism and survival, because of a lack of asparagine synthetase activity. Erwinia-derived asparaginase reduces circulating levels of asparagine by catalyzing the deamidation of asparagine to aspartic acid and ammonia. The reduction of circulating asparagine results in cytotoxicity specific for leukemic cells by depriving them of their source of the amino acid.

*For PDFs of the full report and accompanying Commentary, click on the links to the left of this introduction.

A supplement to Clinical Endocrinology News.
This supplement was sponsored by Amylin.

• Introduction
• Should Minimal Blood Glucose Variability Become the Gold Standard of Glycemic Control?
• Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients
• Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes
• Effects of Intensive Glucose Lowering in Type 2 Diabetes
• Pramlintide as an Adjunct to Insulin in Patients With Type 2 Diabetes in a Clinical Practice Setting Reduced A1C, Postprandial Glucose Excursions, and Weight
• Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes: A 1-Year Randomized Controlled Trial
• Amylin Replacement with Primlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Type 1 Diabetes Mellitus: A 1-Year, Randomized Controlled Trial
• Important Safety Information and SYMLIN Prescribing Information

Faculty/Faculty Disclosure

Steven V. Edelman, MD
Professor of Medicine, University of California, San Diego
Veterans Affairs Medical Center, San Diego, California
Founder and Director, Taking Control of Your Diabetes, 501(3)
Del Mar, California
Associate Clinical Professor of Medicine
Dr. Edelman is a consultant to and speaker for Amylin Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, and sanofi-aventis U.S., LLC.

Copyright © 2009 Elsevier Inc.

A supplement to Clinical Endocrinology News.
This supplement was sponsored by Amylin.

• Introduction
• Should Minimal Blood Glucose Variability Become the Gold Standard of Glycemic Control?
• Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients
• Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes
• Effects of Intensive Glucose Lowering in Type 2 Diabetes
• Pramlintide as an Adjunct to Insulin in Patients With Type 2 Diabetes in a Clinical Practice Setting Reduced A1C, Postprandial Glucose Excursions, and Weight
• Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes: A 1-Year Randomized Controlled Trial
• Amylin Replacement with Primlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Type 1 Diabetes Mellitus: A 1-Year, Randomized Controlled Trial
• Important Safety Information and SYMLIN Prescribing Information

Faculty/Faculty Disclosure

Steven V. Edelman, MD
Professor of Medicine, University of California, San Diego
Veterans Affairs Medical Center, San Diego, California
Founder and Director, Taking Control of Your Diabetes, 501(3)
Del Mar, California
Associate Clinical Professor of Medicine
Dr. Edelman is a consultant to and speaker for Amylin Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, and sanofi-aventis U.S., LLC.

Copyright © 2009 Elsevier Inc.

A supplement to Clinical Endocrinology News.
This supplement was sponsored by Amylin.

• Introduction
• Should Minimal Blood Glucose Variability Become the Gold Standard of Glycemic Control?
• Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients
• Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes
• Effects of Intensive Glucose Lowering in Type 2 Diabetes
• Pramlintide as an Adjunct to Insulin in Patients With Type 2 Diabetes in a Clinical Practice Setting Reduced A1C, Postprandial Glucose Excursions, and Weight
• Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes: A 1-Year Randomized Controlled Trial
• Amylin Replacement with Primlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Type 1 Diabetes Mellitus: A 1-Year, Randomized Controlled Trial
• Important Safety Information and SYMLIN Prescribing Information

Faculty/Faculty Disclosure

Steven V. Edelman, MD
Professor of Medicine, University of California, San Diego
Veterans Affairs Medical Center, San Diego, California
Founder and Director, Taking Control of Your Diabetes, 501(3)
Del Mar, California
Associate Clinical Professor of Medicine
Dr. Edelman is a consultant to and speaker for Amylin Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, and sanofi-aventis U.S., LLC.

Copyright © 2009 Elsevier Inc.

BOSTON – Children who present to the emergency department with the classic "seat-belt sign" may have intra-abdominal injuries that warrant further investigation, even when they do not exhibit abdominal pain or tenderness, reported investigators at the annual meeting of the Pediatric Academic Societies.

The seat-belt sign – a continuous area of erythema, ecchymosis, or contusion caused by seat-belt pressure during a vehicle collision or impact – was significantly associated with risk for any intra-abdominal injury, reported Dr. Angela Ellison, an emergency physician at the Children’s Hospital of Philadelphia.

One-third of children with the seat-belt sign did not have abdominal pain or tenderness, yet 10% of those who also had an abdominal CT scan were found to have an intra-abdominal injury.

"Children with seat-belt sign are at high risk of intra-abdominal injury, primarily gastrointestinal injury, and are more likely to undergo acute intervention for intra-abdominal injury," Dr. Ellison said, speaking on behalf of colleagues in the Pediatric Emergency Care Applied Research Network.

The investigators analyzed a subset of patients from a prospective multicenter study of children presenting to 20 emergency departments with blunt torso trauma. They identified 3,740 children younger than 18 years with blunt abdominal trauma from a motor vehicle collision, excluding those with injuries older than 24 hours, those with preexisting neurologic disorders, and those transferred with prior abdominal images.

To scan or not to scan was left to the discretion of the treating physician, and clinical data, including findings of the presence or absence of a seat-belt sign, were collected. Patients were followed with a telephone call at 1 week if they were discharged after treatment or with medical records if they were admitted.

The authors found that 585 children (16%) had the seat-belt sign, and 3,155 (84%) did not. In all, 443 patients with the sign (76%) had an abdominal CT, compared with 1,415 (45%) of those lacking the sign (P less than .001). In total, 50% of the study population had an abdominal CT.

Among the patients who underwent CT, 19% of those with the seat-belt sign had some form of intra-abdominal injury, compared with 11% of those who had CT scans but no seat-belt sign (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3-2.1). Gastrointestinal injuries were the most common, occurring in 10% of the seat-belt sign patients and 1% of those with no sign (RR, 9.8; 95% CI, 5.5-17.4). There were no significant differences between the groups in rates of injury to the spleen, liver, kidney, or pancreas.

In multivariate analysis, they found that factors significantly associated with a risk for any intra-abdominal injury were the seat-belt sign (RR, 1.7; P less than .01), hypotension (RR, 2.6; P less than .01), Glasgow Coma Scale score less than 14 (RR, 2.2; P less than .01), decreased breath sounds (RR, 1.7; P = .03), abdominal tenderness (RR, 1.6; P less than .01), and evidence of thoracic trauma (RR, 1.4; P = .03).

Patients with the seat-belt sign were significantly more likely to undergo any acute intervention for intra-abdominal injury (RR, 4.5; 95% CI, 3.0-6.8), nothing-by-mouth orders and intravenous fluids for more than 2 nights (RR, 14.6; 95% CI, 7.1-29.9), laparotomy (RR, 9.5; 95% CI, 5.6-16.1), or blood transfusion (RR, 2.9; 95% CI, 1.6-5.1).

Of the 196 patients with the seat-belt sign but no abdominal pain or tenderness (34%), 103 had abdominal CT and, of this group, 11 (10.7%) had an intra-abdominal injury diagnosed. Of all 196 patients, 4 (2%) required an acute intervention for their injuries.

"Children with seat-belt sign and no abdominal pain or tenderness have a high risk of acute abdominal injury and a non-negligible risk of undergoing acute interventions for intra-abdominal injury. Therefore, we recommend that clinicians strongly consider additional evaluation in this subpopulation of patients," Dr. Ellison said.

The study was supported by the National Center for Injury Prevention and Control and the Health Resources and Services Administration. Dr. Ellison and coauthors reported having no conflicts of interest.

BOSTON – Children who present to the emergency department with the classic "seat-belt sign" may have intra-abdominal injuries that warrant further investigation, even when they do not exhibit abdominal pain or tenderness, reported investigators at the annual meeting of the Pediatric Academic Societies.

The seat-belt sign – a continuous area of erythema, ecchymosis, or contusion caused by seat-belt pressure during a vehicle collision or impact – was significantly associated with risk for any intra-abdominal injury, reported Dr. Angela Ellison, an emergency physician at the Children’s Hospital of Philadelphia.

One-third of children with the seat-belt sign did not have abdominal pain or tenderness, yet 10% of those who also had an abdominal CT scan were found to have an intra-abdominal injury.

"Children with seat-belt sign are at high risk of intra-abdominal injury, primarily gastrointestinal injury, and are more likely to undergo acute intervention for intra-abdominal injury," Dr. Ellison said, speaking on behalf of colleagues in the Pediatric Emergency Care Applied Research Network.

The investigators analyzed a subset of patients from a prospective multicenter study of children presenting to 20 emergency departments with blunt torso trauma. They identified 3,740 children younger than 18 years with blunt abdominal trauma from a motor vehicle collision, excluding those with injuries older than 24 hours, those with preexisting neurologic disorders, and those transferred with prior abdominal images.

To scan or not to scan was left to the discretion of the treating physician, and clinical data, including findings of the presence or absence of a seat-belt sign, were collected. Patients were followed with a telephone call at 1 week if they were discharged after treatment or with medical records if they were admitted.

The authors found that 585 children (16%) had the seat-belt sign, and 3,155 (84%) did not. In all, 443 patients with the sign (76%) had an abdominal CT, compared with 1,415 (45%) of those lacking the sign (P less than .001). In total, 50% of the study population had an abdominal CT.

Among the patients who underwent CT, 19% of those with the seat-belt sign had some form of intra-abdominal injury, compared with 11% of those who had CT scans but no seat-belt sign (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3-2.1). Gastrointestinal injuries were the most common, occurring in 10% of the seat-belt sign patients and 1% of those with no sign (RR, 9.8; 95% CI, 5.5-17.4). There were no significant differences between the groups in rates of injury to the spleen, liver, kidney, or pancreas.

In multivariate analysis, they found that factors significantly associated with a risk for any intra-abdominal injury were the seat-belt sign (RR, 1.7; P less than .01), hypotension (RR, 2.6; P less than .01), Glasgow Coma Scale score less than 14 (RR, 2.2; P less than .01), decreased breath sounds (RR, 1.7; P = .03), abdominal tenderness (RR, 1.6; P less than .01), and evidence of thoracic trauma (RR, 1.4; P = .03).

Patients with the seat-belt sign were significantly more likely to undergo any acute intervention for intra-abdominal injury (RR, 4.5; 95% CI, 3.0-6.8), nothing-by-mouth orders and intravenous fluids for more than 2 nights (RR, 14.6; 95% CI, 7.1-29.9), laparotomy (RR, 9.5; 95% CI, 5.6-16.1), or blood transfusion (RR, 2.9; 95% CI, 1.6-5.1).

Of the 196 patients with the seat-belt sign but no abdominal pain or tenderness (34%), 103 had abdominal CT and, of this group, 11 (10.7%) had an intra-abdominal injury diagnosed. Of all 196 patients, 4 (2%) required an acute intervention for their injuries.

"Children with seat-belt sign and no abdominal pain or tenderness have a high risk of acute abdominal injury and a non-negligible risk of undergoing acute interventions for intra-abdominal injury. Therefore, we recommend that clinicians strongly consider additional evaluation in this subpopulation of patients," Dr. Ellison said.

The study was supported by the National Center for Injury Prevention and Control and the Health Resources and Services Administration. Dr. Ellison and coauthors reported having no conflicts of interest.

BOSTON – Children who present to the emergency department with the classic "seat-belt sign" may have intra-abdominal injuries that warrant further investigation, even when they do not exhibit abdominal pain or tenderness, reported investigators at the annual meeting of the Pediatric Academic Societies.

The seat-belt sign – a continuous area of erythema, ecchymosis, or contusion caused by seat-belt pressure during a vehicle collision or impact – was significantly associated with risk for any intra-abdominal injury, reported Dr. Angela Ellison, an emergency physician at the Children’s Hospital of Philadelphia.

One-third of children with the seat-belt sign did not have abdominal pain or tenderness, yet 10% of those who also had an abdominal CT scan were found to have an intra-abdominal injury.

"Children with seat-belt sign are at high risk of intra-abdominal injury, primarily gastrointestinal injury, and are more likely to undergo acute intervention for intra-abdominal injury," Dr. Ellison said, speaking on behalf of colleagues in the Pediatric Emergency Care Applied Research Network.

The investigators analyzed a subset of patients from a prospective multicenter study of children presenting to 20 emergency departments with blunt torso trauma. They identified 3,740 children younger than 18 years with blunt abdominal trauma from a motor vehicle collision, excluding those with injuries older than 24 hours, those with preexisting neurologic disorders, and those transferred with prior abdominal images.

To scan or not to scan was left to the discretion of the treating physician, and clinical data, including findings of the presence or absence of a seat-belt sign, were collected. Patients were followed with a telephone call at 1 week if they were discharged after treatment or with medical records if they were admitted.

The authors found that 585 children (16%) had the seat-belt sign, and 3,155 (84%) did not. In all, 443 patients with the sign (76%) had an abdominal CT, compared with 1,415 (45%) of those lacking the sign (P less than .001). In total, 50% of the study population had an abdominal CT.

Among the patients who underwent CT, 19% of those with the seat-belt sign had some form of intra-abdominal injury, compared with 11% of those who had CT scans but no seat-belt sign (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3-2.1). Gastrointestinal injuries were the most common, occurring in 10% of the seat-belt sign patients and 1% of those with no sign (RR, 9.8; 95% CI, 5.5-17.4). There were no significant differences between the groups in rates of injury to the spleen, liver, kidney, or pancreas.

In multivariate analysis, they found that factors significantly associated with a risk for any intra-abdominal injury were the seat-belt sign (RR, 1.7; P less than .01), hypotension (RR, 2.6; P less than .01), Glasgow Coma Scale score less than 14 (RR, 2.2; P less than .01), decreased breath sounds (RR, 1.7; P = .03), abdominal tenderness (RR, 1.6; P less than .01), and evidence of thoracic trauma (RR, 1.4; P = .03).

Patients with the seat-belt sign were significantly more likely to undergo any acute intervention for intra-abdominal injury (RR, 4.5; 95% CI, 3.0-6.8), nothing-by-mouth orders and intravenous fluids for more than 2 nights (RR, 14.6; 95% CI, 7.1-29.9), laparotomy (RR, 9.5; 95% CI, 5.6-16.1), or blood transfusion (RR, 2.9; 95% CI, 1.6-5.1).

Of the 196 patients with the seat-belt sign but no abdominal pain or tenderness (34%), 103 had abdominal CT and, of this group, 11 (10.7%) had an intra-abdominal injury diagnosed. Of all 196 patients, 4 (2%) required an acute intervention for their injuries.

"Children with seat-belt sign and no abdominal pain or tenderness have a high risk of acute abdominal injury and a non-negligible risk of undergoing acute interventions for intra-abdominal injury. Therefore, we recommend that clinicians strongly consider additional evaluation in this subpopulation of patients," Dr. Ellison said.

The study was supported by the National Center for Injury Prevention and Control and the Health Resources and Services Administration. Dr. Ellison and coauthors reported having no conflicts of interest.

A Case Studies Compendium supplement to Clinical Endocrinology News. This supplement was sponsored by Daiichi Sankyo, Inc.

• Background
• Current Visit
• Laboratory Results
• Clinical Discussion
• Endocrinologist Consultation
• New Treatment Regimen With Add-On Therapy
• Conclusions

Case 2 Topics

• Background
• Current Visit: Exam Findings
• Current Treatment Regimen
• Health History
• Laboratory Results
• Clinical Discussion
• Cardiologist Visit
• Three Months After Visiting the Cardiologist
• Add-On Therapy With Welchol for Patients With T2DM and CHD
• Treatment Goals for Alice
• Conclusions

Faculty/Faculty Disclosures

Yehuda Handelsman, MD, FACP, FACE
Medical Director
Metabolic Institute of America
Chair and Program Director
7th World Congress on InsulinResistance
Chair, International Committeefor Insulin Resistance
18372 Clark Street, Suite 212
Tarzana, CA 91356
E-mail:yhandelsman@pacbell.net
Web Site:www.TheMetabolicCenter.com
Dr Handelsman is a consultant for Bristol-Myers Squibb

Company, Daiichi Sankyo, Inc., GlaxoSmithKline, Medtronic, Merck, Tethys,

and Xoma; he has received clinical research grant funding from Daiichi Sankyo, Inc., GlaxoSmithKline, Novo Nordisk, and Takeda; and he ison the speakers bureau for AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Inc., GlaxoSmithKline, Merck, and Novartis. He also serves on the advisory board for CLINICAL ENDOCRINOLOGY NEWS.

Peter H. Jones, MD, FACP
Co-Director, Lipid Metabolism
and Atherosclerosis Clinic
Medical Director, Weight
Management Center
The Methodist Hospital
Associate Professor of Medicine
Section of Atherosclerosis andLipid Research
Baylor College of Medicine
Houston, TX 77030
E-mail: jones@bcm.tmc.edu
Dr Jones has disclosed that he has received support in the form of consulting agreements from Abbott Laboratories, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo, Inc., and Merck.

Copyright © 2010 Elsevier Inc.

To view the supplement, click the image above.

A Case Studies Compendium supplement to Clinical Endocrinology News. This supplement was sponsored by Daiichi Sankyo, Inc.

• Background
• Current Visit
• Laboratory Results
• Clinical Discussion
• Endocrinologist Consultation
• New Treatment Regimen With Add-On Therapy
• Conclusions

Case 2 Topics

• Background
• Current Visit: Exam Findings
• Current Treatment Regimen
• Health History
• Laboratory Results
• Clinical Discussion
• Cardiologist Visit
• Three Months After Visiting the Cardiologist
• Add-On Therapy With Welchol for Patients With T2DM and CHD
• Treatment Goals for Alice
• Conclusions

Faculty/Faculty Disclosures

Yehuda Handelsman, MD, FACP, FACE
Medical Director
Metabolic Institute of America
Chair and Program Director
7th World Congress on InsulinResistance
Chair, International Committeefor Insulin Resistance
18372 Clark Street, Suite 212
Tarzana, CA 91356
E-mail:yhandelsman@pacbell.net
Web Site:www.TheMetabolicCenter.com
Dr Handelsman is a consultant for Bristol-Myers Squibb

Company, Daiichi Sankyo, Inc., GlaxoSmithKline, Medtronic, Merck, Tethys,

and Xoma; he has received clinical research grant funding from Daiichi Sankyo, Inc., GlaxoSmithKline, Novo Nordisk, and Takeda; and he ison the speakers bureau for AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Inc., GlaxoSmithKline, Merck, and Novartis. He also serves on the advisory board for CLINICAL ENDOCRINOLOGY NEWS.

Peter H. Jones, MD, FACP
Co-Director, Lipid Metabolism
and Atherosclerosis Clinic
Medical Director, Weight
Management Center
The Methodist Hospital
Associate Professor of Medicine
Section of Atherosclerosis andLipid Research
Baylor College of Medicine
Houston, TX 77030
E-mail: jones@bcm.tmc.edu
Dr Jones has disclosed that he has received support in the form of consulting agreements from Abbott Laboratories, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo, Inc., and Merck.

Copyright © 2010 Elsevier Inc.

To view the supplement, click the image above.

A Case Studies Compendium supplement to Clinical Endocrinology News. This supplement was sponsored by Daiichi Sankyo, Inc.

• Background
• Current Visit
• Laboratory Results
• Clinical Discussion
• Endocrinologist Consultation
• New Treatment Regimen With Add-On Therapy
• Conclusions

Case 2 Topics

• Background
• Current Visit: Exam Findings
• Current Treatment Regimen
• Health History
• Laboratory Results
• Clinical Discussion
• Cardiologist Visit
• Three Months After Visiting the Cardiologist
• Add-On Therapy With Welchol for Patients With T2DM and CHD
• Treatment Goals for Alice
• Conclusions

Faculty/Faculty Disclosures

Yehuda Handelsman, MD, FACP, FACE
Medical Director
Metabolic Institute of America
Chair and Program Director
7th World Congress on InsulinResistance
Chair, International Committeefor Insulin Resistance
18372 Clark Street, Suite 212
Tarzana, CA 91356
E-mail:yhandelsman@pacbell.net
Web Site:www.TheMetabolicCenter.com
Dr Handelsman is a consultant for Bristol-Myers Squibb

Company, Daiichi Sankyo, Inc., GlaxoSmithKline, Medtronic, Merck, Tethys,

and Xoma; he has received clinical research grant funding from Daiichi Sankyo, Inc., GlaxoSmithKline, Novo Nordisk, and Takeda; and he ison the speakers bureau for AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Inc., GlaxoSmithKline, Merck, and Novartis. He also serves on the advisory board for CLINICAL ENDOCRINOLOGY NEWS.

Peter H. Jones, MD, FACP
Co-Director, Lipid Metabolism
and Atherosclerosis Clinic
Medical Director, Weight
Management Center
The Methodist Hospital
Associate Professor of Medicine
Section of Atherosclerosis andLipid Research
Baylor College of Medicine
Houston, TX 77030
E-mail: jones@bcm.tmc.edu
Dr Jones has disclosed that he has received support in the form of consulting agreements from Abbott Laboratories, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo, Inc., and Merck.

Copyright © 2010 Elsevier Inc.

To view the supplement, click the image above.