Current Psychiatry

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

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.

Dr. Scott Freeman’s useful discussion of targeting acute risk factors in suicidal patients (“Suicide assessment: Targeting acute risk factors,” Current Psychiatry, January 2012, p. 52-57) ends by resolving the clinical vignette with a summary of hospital treatment. Apart from failing to indicate any psychotherapeutic inroads, Dr. Freeman seems to support prescribing clonazepam, 0.5 mg twice daily and 1 mg at bedtime. Clonazepam apparently “worked” by alleviating the patient’s anxiety and insomnia, but defied any pharmacologic rationale insofar as clonazepam has a slow onset and long half-life, making 3 doses per day irrational. This treatment strategy also risks problems of cumulative excess in the long run after discharge.

Aggressive pharmacotherapy may be the hallmark of modern acute hospital treatment, but surely it should incorporate careful understanding of specific medications’ pharmacodynamics, especially when relying on benzodiazepines. Needless to say, beginning a psychological process in the hospital also appears to have been shortchanged.

Sara Hartley, MD
Lecturer, Clinical Skills Program
University of California,
Berkeley-University of California,
San Francisco Joint Medical Program
Berkeley, CA

Dr. Freeman responds

I appreciate Dr. Hartley’s interest in my article. Although I agree with her that psychotherapy is an integral part of any treatment plan, the clinical vignette was used only to emphasize the need to aggressively and quickly start antidepressant and, more importantly, anxiolytic pharmacologic treatment in acutely suicidal patients with severe anxiety and depression.

With regard to clonazepam’s pharmacokinetics, although it does have a long half-life, it is only weakly lipophilic compared with other long-acting benzodiazepines such as diazepam. In fact, clonazepam has been shown to be less lipophilic than lorazepam,¹ meaning it has a much smaller volume of distribution and less accumulation in peripheral adipose tissue. Therefore, one would not be concerned about significant drug accumulation leading to unexpected toxicity with a less lipophilic agent such as clonazepam.

I do not agree that dosing clonazepam 3 times a day, especially in an acute crisis, is “irrational,” as Dr. Hartley suggests. According to the package insert, although clonazepam is recommended to be administered twice daily for panic disorder, it can be given 3 times a day for seizure disorders.²

Scott A. Freeman, MD
Medical Director
Schizophrenia and Bipolar Disorder Inpatient Unit
McLean Hospital
Belmont, MA

Dr. Scott Freeman’s useful discussion of targeting acute risk factors in suicidal patients (“Suicide assessment: Targeting acute risk factors,” Current Psychiatry, January 2012, p. 52-57) ends by resolving the clinical vignette with a summary of hospital treatment. Apart from failing to indicate any psychotherapeutic inroads, Dr. Freeman seems to support prescribing clonazepam, 0.5 mg twice daily and 1 mg at bedtime. Clonazepam apparently “worked” by alleviating the patient’s anxiety and insomnia, but defied any pharmacologic rationale insofar as clonazepam has a slow onset and long half-life, making 3 doses per day irrational. This treatment strategy also risks problems of cumulative excess in the long run after discharge.

Aggressive pharmacotherapy may be the hallmark of modern acute hospital treatment, but surely it should incorporate careful understanding of specific medications’ pharmacodynamics, especially when relying on benzodiazepines. Needless to say, beginning a psychological process in the hospital also appears to have been shortchanged.

Sara Hartley, MD
Lecturer, Clinical Skills Program
University of California,
Berkeley-University of California,
San Francisco Joint Medical Program
Berkeley, CA

Dr. Freeman responds

I appreciate Dr. Hartley’s interest in my article. Although I agree with her that psychotherapy is an integral part of any treatment plan, the clinical vignette was used only to emphasize the need to aggressively and quickly start antidepressant and, more importantly, anxiolytic pharmacologic treatment in acutely suicidal patients with severe anxiety and depression.

With regard to clonazepam’s pharmacokinetics, although it does have a long half-life, it is only weakly lipophilic compared with other long-acting benzodiazepines such as diazepam. In fact, clonazepam has been shown to be less lipophilic than lorazepam,¹ meaning it has a much smaller volume of distribution and less accumulation in peripheral adipose tissue. Therefore, one would not be concerned about significant drug accumulation leading to unexpected toxicity with a less lipophilic agent such as clonazepam.

I do not agree that dosing clonazepam 3 times a day, especially in an acute crisis, is “irrational,” as Dr. Hartley suggests. According to the package insert, although clonazepam is recommended to be administered twice daily for panic disorder, it can be given 3 times a day for seizure disorders.²

Scott A. Freeman, MD
Medical Director
Schizophrenia and Bipolar Disorder Inpatient Unit
McLean Hospital
Belmont, MA

Dr. Scott Freeman’s useful discussion of targeting acute risk factors in suicidal patients (“Suicide assessment: Targeting acute risk factors,” Current Psychiatry, January 2012, p. 52-57) ends by resolving the clinical vignette with a summary of hospital treatment. Apart from failing to indicate any psychotherapeutic inroads, Dr. Freeman seems to support prescribing clonazepam, 0.5 mg twice daily and 1 mg at bedtime. Clonazepam apparently “worked” by alleviating the patient’s anxiety and insomnia, but defied any pharmacologic rationale insofar as clonazepam has a slow onset and long half-life, making 3 doses per day irrational. This treatment strategy also risks problems of cumulative excess in the long run after discharge.

Aggressive pharmacotherapy may be the hallmark of modern acute hospital treatment, but surely it should incorporate careful understanding of specific medications’ pharmacodynamics, especially when relying on benzodiazepines. Needless to say, beginning a psychological process in the hospital also appears to have been shortchanged.

Sara Hartley, MD
Lecturer, Clinical Skills Program
University of California,
Berkeley-University of California,
San Francisco Joint Medical Program
Berkeley, CA

Dr. Freeman responds

I appreciate Dr. Hartley’s interest in my article. Although I agree with her that psychotherapy is an integral part of any treatment plan, the clinical vignette was used only to emphasize the need to aggressively and quickly start antidepressant and, more importantly, anxiolytic pharmacologic treatment in acutely suicidal patients with severe anxiety and depression.

With regard to clonazepam’s pharmacokinetics, although it does have a long half-life, it is only weakly lipophilic compared with other long-acting benzodiazepines such as diazepam. In fact, clonazepam has been shown to be less lipophilic than lorazepam,¹ meaning it has a much smaller volume of distribution and less accumulation in peripheral adipose tissue. Therefore, one would not be concerned about significant drug accumulation leading to unexpected toxicity with a less lipophilic agent such as clonazepam.

I do not agree that dosing clonazepam 3 times a day, especially in an acute crisis, is “irrational,” as Dr. Hartley suggests. According to the package insert, although clonazepam is recommended to be administered twice daily for panic disorder, it can be given 3 times a day for seizure disorders.²

Scott A. Freeman, MD
Medical Director
Schizophrenia and Bipolar Disorder Inpatient Unit
McLean Hospital
Belmont, MA