Mr. M, a world-class athlete, collapsed suddenly in an alley. He was rushed to a hospital emergency room, where he nearly died of internal bleeding from a grapefruit-sized abdominal lymphoma. He was hospitalized and placed on chemotherapy.

Increasing doses of opiates hardly reduced his pain, and he became extremely anxious. Staff described him as “climbing the walls.” He lay in bed writhing, and his parents feared he was becoming a “drug addict.”

Anxiety about his life-threatening illness was clearly compounding his pain, so his attending physician ordered a psychiatric evaluation. When I interviewed the patient, I felt that hypnosis could help.

Hypnosis—as a state of highly focused attention—can help us treat patients’ anxiety, phobias, pain, posttraumatic stress disorder (PTSD), and dissociative disorders. With training, an experienced psychiatrist can quickly start using hypnosis as an adjunct to other therapies.

This article describes how hypnosis helped Mr. M and a young woman traumatized by a criminal assault. Based on my experience and the literature, I discuss what hypnosis is, what training is required, how to measure hypnotizability, and the value of hypnosis in helping patients control their anxiety, posttraumatic, and dissociative states.

Case continued: ‘Surfing’ in Hawaii

When I met Mr. M in the hospital, I acknowledged his distress and the reasons for it, saying “You don’t really want to be here, do you?”

“How many years of medical training did it take you to figure that out?” he replied.

“Well then,” I said, “let’s go somewhere else. Where would you like to be right now?”

He responded, “I’ve never surfed.”

“Good,” I replied, “let’s go to Hawaii.” In hypnosis, I had him picture himself surfing. He continued to groan, but the pattern changed. “What happened?” I asked. “I fell off the surfboard,” he replied. “OK, get back on, and do it right,” I told him.

He learned to practice self-hypnosis, which markedly reduced his anxiety and pain. Two days later he was off pain medications and joking with the nurses in the hall. The attending physician noted in the patient’s record: “Patient off pain meds. Tumor must be regressing.”

What is hypnosis?

Mr. M’s response, though unusually strong, underscores the fact that hypnosis can rapidly produce analgesia and anxiolysis in the medical setting. Hypnosis—often called “believed-in imagination”—is characterized by an ability to sustain a state of attentive, receptive, intense focal concentration with diminished peripheral awareness. The hypnotized person is awake and alert, not asleep. Hypnosis’ three main components are absorption, dissociation, and suggestibility.

Biological basis. The hypnotic state has no brain “signature” per se, but brain imaging portrays hypnosis as a state of alertness with altered anterior cingulate gyrus activation, which helps to focus attention.^1-3 Hypnotized persons can demonstrably alter blood flow in brain regions involved in perceptual processing in response to suggestions of altered perception, whether somatosensory, visual, or olfactory.^4,5 Thus, patients report not only reduced pain but changes in how they experience pain with hypnotic analgesia.

The brain’s dopamine neurotransmitter system—especially in the frontal lobes—also may be involved in hypnosis, as highly hypnotizable persons have elevated levels of dopamine metabolites in their cerebrospinal fluid.⁶

Hypnotic trance. The trance experience is often best explained to patients as similar to being absorbed in a good novel. One loses awareness of one’s surroundings and enters the imagined world. When the novel is finished, the reader requires a moment of reorientation to the surrounding world.

A trance is a state of sustained, attentive-receptive concentration in response to a signal from within or from someone else. The signal activates this shift of awareness and permits more-intensive concentration in a designated direction.

All hypnosis is self-hypnosis. Much of its clinical value is that it can be self-induced throughout the day and whenever symptoms emerge. During the first weeks, patients can be encouraged to practice every 1 or 2 hours.

Applying hypnosis to practice. A well-trained clinician can learn to use hypnosis in classes offered by the two professional hypnosis societies or the American Psychiatric Association (Box 1) Because hypnosis is not something “done to” a patient but rather a capacity to be measured, tapped, and utilized, psychiatrists can integrate hypnosis into clinical practice after some initial training, with ongoing learning and supervision.

Who can be hypnotized?

Not everyone is equally hypnotizable, and hypnotizability is a stable and measurable trait. Approximately one-quarter of adults cannot respond to hypnotic instructions, whereas 10% are extremely hypnotizable.⁷

Brief, clinically useful tests of hypnotic responsiveness have been developed, such as the Hypnotic Induction Profile (HIP).⁸ The clinician usually can induce the trance experience and systematically measure the patient’s response within 5 minutes. A HIP score of 5 indicates usable hypnotizability.

The HIP test includes instructions to produce a sense of lightness in the left arm and hand, with tests of response to this instruction. Response is characterized by dissociation, hand elevation after it is lowered, involuntariness, response to the cutoff signal, and altered sensation.

Turning hypnotic induction into a test of hypnotic capacity transforms the initial encounter by:

• removing pressure on the clinician to successfully hypnotize the subject
• reducing patients’ experiences of complying with the clinician’s wishes, rather than exploring and discovering their own hypnotic capacity.

Placing the hypnotic experience in the context of a test also makes it consonant with other medical examinations and procedures.⁸

Once a patient’s hypnotizability is determined, structured measurement is no longer necessary. The test-retest correlation for hypnotizability scores is 0.7 over 25 years, which is more consistent than IQ testing.⁷ Subsequent inductions usually can be generated by the patient or signaled by the clinician, and only seconds are required for the shift into trance.

Box 1

Reducing anxiety

Anxiety can be understood as a vaguely defined but immobilizing sense of distress. Lack of clarity about the discomfort’s source enhances the patient’s sense of helplessness and avoidance. One therapeutic challenge is to convert anxiety into fear—to give it a focus so that something can be done about it.

Box 2

Anxiety sets up a negative feedback cycle between psychological preoccupation and somatic discomfort, a “snowball effect” in which subjective anxiety and somatic tension reinforce each other. Hypnosis can help reduce anxiety and induce relaxation,⁹ and its dissociative component can help separate anxiety’s psychological and somatic components.

Hypnosis is as effective at reducing anxiety as 1 mg of alprazolam, at least in a study of college students.¹⁰ Student volunteers with high and low hypnotizability were given alprazolam, 1 mg, and a hypnotic suggestion based on their reactions to the drug. Four days later, when students received hypnosis only and hypnosis plus alprazolam:

• combination therapy reduced anxiety more effectively than did hypnosis or alprazolam alone, as measured by the Profile of Mood States tension-anxiety scale
• improvement was comparable with hypnosis or alprazolam alone
• highly hypnotizable students showed significantly greater relaxation than did those with low hypnotizability in all three treatment groups
• EEG data showed similar frontal and occipital changes in the alprazolam and hypnotic suggestion groups.

In randomized trials, simple self-hypnosis training has reduced pain and anxiety during medical procedures, reducing procedure time by an average 17 minutes and resulting in fewer complications.¹¹

A typical hypnotic instruction for managing anxiety is provided in Box 2. This approach teaches patients how to deal with stressors that complicate their anxiety and to control their somatic response. Hypnosis expands patients’ repertoire of responses and enables them to feel less helpless.

Confronting phobias

Phobic symptoms of fear and avoidance or exposure with distress respond especially well to brief hypnosis interventions. Although behavior modification and antidepressants also can treat phobias successfully, one or two hypnosis sessions often can reduce or cure phobic symptoms.

For example, one can help patients with airplane phobia prepare for flight by going into a hypnotic state and learning three concepts:

• Think of the airplane as an extension of the body, such as a bicycle.
• Float with the plane.
• Think about the difference between probability and possibility.

The hypnotic state—with its focused attention and physical relaxation—can amplify this cognitive restructuring technique. Phobic patients can feel more in control of their somatic reactions and, by extrapolation, the flying experience itself. In one study, 52% of patients taught this self-hypnosis exercise remained improved or cured at least 7 years later.¹²

Treating traumatic reactions

Evidence is growing that trauma elicits dissociation. Thus, hypnosis could help us understand and treat traumatic reactions, including patients with acute and posttraumatic stress disorder (PTSD) and dissociative disorders.

The hypnotic state’s controlled dissociation can be used to model the uncontrolled dissociation represented by posttraumatic phenomena such as flashbacks, numbing, and amnesia.¹³ This view is supported by evidence that PTSD is associated with high hypnotizability.^14,15

Acute stress disorder—as introduced in DSM-IV¹⁶—is characterized by prominent dissociative symptoms, with intrusion, avoidance, and hyperarousal. These diagnostic criteria recognize that acute dissociation is a common and predictable reaction to trauma.

Hypnosis involving grief work, exploration of trauma-related transference issues, and emotional expression are effective psychotherapies for persons exposed to trauma. Becoming familiar with hypnotic states can teach patients to recognize, understand, and control their dissociative states.

Evidence suggests that hypnosis’ intense concentration may reverse the dissociative mind fragmentation caused by trauma.¹⁷ Traumatic memories may seem less overwhelming and intrusive once patients discover they can:

• exert greater control over memory access and retrieval
• work through and assimilate disturbing thoughts.

The controlled experience of hypnotic abreaction (reliving traumatic and other memories with strong emotion) provides boundaries for psychotherapeutic grief work.^18,19 Instead of telling patients not to ruminate over a traumatic event, the clinician instructs the patient how to think about the experience.

The inferred message is that the patient can work on other things—such as relationships and daily living problems—after this therapeutic work is done.

Patients are slowly separated from the victim role. The goal is to help them restructure their memories, both cognitively and emotionally. They bear the memories’ impact, yet come to see the information differently.⁷ Traumatic input becomes more bearable when linked to a cognitively restructured recognition of an adaptive response.^,20 For example, patients may acknowledge what they did during a traumatic event that was self-protective or helped others.

PTSD. Hypnosis shares common elements with other cognitive and behavioral treatments for PTSD, including exposure to traumatic memories for cognitive and emotional processing. Few studies have examined using hypnosis to treat PTSD, but evidence suggests it is at least as effective as other cognitive-behavioral treatments.^20,21

Patients can be taught to view PTSD’s intrusive memories and bodily symptoms as re-experiencing painful memories. The memories often intrude less frequently after patients find a controlled method—such as self-hypnosis—to access and work them through.²²

Box 3

Self-blame. Many trauma victims would rather feel guilty than helpless. They blame themselves inappropriately for events over which they had no control, rather than accept their helplessness. They misuse hindsight about the trauma to assume the events were predictable and therefore avoidable. They imagine they can replay the events and change the outcome.

Such an approach to trauma can be profoundly demoralizing, leaving victims burdened by needless guilt and shame. Helping them face and bear the feelings associated with traumatic events can free them from efforts to “undo” or take responsibility for the trauma and accept what happened.

Split-screen technique. Using hypnosis with a “split-screen” technique can help patients restructure the memory of trauma. The left screen symbolizes the trauma in condensed form. The right screen helps patients focus on how they tried to master the situation. This grief work allows patients to acknowledge, bear, and put into perspective the humiliation of the experience and their loss of invulnerability, health, or loved ones (Box 3).¹⁸

Dissociation. Dissociating during a threatening situation may enable a person to put aside some awareness of the danger and take self-protective action. Persistent dissociation, however, may make it too easy to avoid working through the traumatic experiences later on.^22-24

Dissociation makes subsequent exposure to reminders of the trauma more similar to a reexperiencing rather than a controlled remembering of it. This can trigger physiologic stress reactions and lead to or worsen PTSD.^25-27

Dissociative disorders can be understood as chronic and severe PTSDs.²⁸ Many individuals with dissociative disorders have histories of sexual and physical abuse.^29-31 Clearly, traumatic experiences sensitize survivors to subsequent trauma through conditioned activation of fear circuitry involving the amygdala, hippocampus, and frontal lobes.³²

Hypnosis can be especially helpful—both for diagnosis and therapy.³³ It can assist the controlled recovery of memories, while allowing some images to remain dissociated from cognition until the patient is ready to deal with them. The patient can turn memories on and off by entering and exiting the hypnotic state and thereby recover and reprocess memories at a tolerable pace.

Related resources

• Society for Clinical and Experimental Hypnosis. http://ijceh.educ.wsu.edu
• American Society of Clinical Hypnosis. www.asch.net
• American Psychological Association, Division 30. Society of Psychological Hypnosis. http://www.apa.org/about/division/div30.html

Mr. M, a world-class athlete, collapsed suddenly in an alley. He was rushed to a hospital emergency room, where he nearly died of internal bleeding from a grapefruit-sized abdominal lymphoma. He was hospitalized and placed on chemotherapy.

Increasing doses of opiates hardly reduced his pain, and he became extremely anxious. Staff described him as “climbing the walls.” He lay in bed writhing, and his parents feared he was becoming a “drug addict.”

Anxiety about his life-threatening illness was clearly compounding his pain, so his attending physician ordered a psychiatric evaluation. When I interviewed the patient, I felt that hypnosis could help.

Hypnosis—as a state of highly focused attention—can help us treat patients’ anxiety, phobias, pain, posttraumatic stress disorder (PTSD), and dissociative disorders. With training, an experienced psychiatrist can quickly start using hypnosis as an adjunct to other therapies.

This article describes how hypnosis helped Mr. M and a young woman traumatized by a criminal assault. Based on my experience and the literature, I discuss what hypnosis is, what training is required, how to measure hypnotizability, and the value of hypnosis in helping patients control their anxiety, posttraumatic, and dissociative states.

Case continued: ‘Surfing’ in Hawaii

When I met Mr. M in the hospital, I acknowledged his distress and the reasons for it, saying “You don’t really want to be here, do you?”

“How many years of medical training did it take you to figure that out?” he replied.

“Well then,” I said, “let’s go somewhere else. Where would you like to be right now?”

He responded, “I’ve never surfed.”

“Good,” I replied, “let’s go to Hawaii.” In hypnosis, I had him picture himself surfing. He continued to groan, but the pattern changed. “What happened?” I asked. “I fell off the surfboard,” he replied. “OK, get back on, and do it right,” I told him.

He learned to practice self-hypnosis, which markedly reduced his anxiety and pain. Two days later he was off pain medications and joking with the nurses in the hall. The attending physician noted in the patient’s record: “Patient off pain meds. Tumor must be regressing.”

What is hypnosis?

Mr. M’s response, though unusually strong, underscores the fact that hypnosis can rapidly produce analgesia and anxiolysis in the medical setting. Hypnosis—often called “believed-in imagination”—is characterized by an ability to sustain a state of attentive, receptive, intense focal concentration with diminished peripheral awareness. The hypnotized person is awake and alert, not asleep. Hypnosis’ three main components are absorption, dissociation, and suggestibility.

Biological basis. The hypnotic state has no brain “signature” per se, but brain imaging portrays hypnosis as a state of alertness with altered anterior cingulate gyrus activation, which helps to focus attention.^1-3 Hypnotized persons can demonstrably alter blood flow in brain regions involved in perceptual processing in response to suggestions of altered perception, whether somatosensory, visual, or olfactory.^4,5 Thus, patients report not only reduced pain but changes in how they experience pain with hypnotic analgesia.

The brain’s dopamine neurotransmitter system—especially in the frontal lobes—also may be involved in hypnosis, as highly hypnotizable persons have elevated levels of dopamine metabolites in their cerebrospinal fluid.⁶

Hypnotic trance. The trance experience is often best explained to patients as similar to being absorbed in a good novel. One loses awareness of one’s surroundings and enters the imagined world. When the novel is finished, the reader requires a moment of reorientation to the surrounding world.

A trance is a state of sustained, attentive-receptive concentration in response to a signal from within or from someone else. The signal activates this shift of awareness and permits more-intensive concentration in a designated direction.

All hypnosis is self-hypnosis. Much of its clinical value is that it can be self-induced throughout the day and whenever symptoms emerge. During the first weeks, patients can be encouraged to practice every 1 or 2 hours.

Applying hypnosis to practice. A well-trained clinician can learn to use hypnosis in classes offered by the two professional hypnosis societies or the American Psychiatric Association (Box 1) Because hypnosis is not something “done to” a patient but rather a capacity to be measured, tapped, and utilized, psychiatrists can integrate hypnosis into clinical practice after some initial training, with ongoing learning and supervision.

Who can be hypnotized?

Not everyone is equally hypnotizable, and hypnotizability is a stable and measurable trait. Approximately one-quarter of adults cannot respond to hypnotic instructions, whereas 10% are extremely hypnotizable.⁷

Brief, clinically useful tests of hypnotic responsiveness have been developed, such as the Hypnotic Induction Profile (HIP).⁸ The clinician usually can induce the trance experience and systematically measure the patient’s response within 5 minutes. A HIP score of 5 indicates usable hypnotizability.

The HIP test includes instructions to produce a sense of lightness in the left arm and hand, with tests of response to this instruction. Response is characterized by dissociation, hand elevation after it is lowered, involuntariness, response to the cutoff signal, and altered sensation.

Turning hypnotic induction into a test of hypnotic capacity transforms the initial encounter by:

• removing pressure on the clinician to successfully hypnotize the subject
• reducing patients’ experiences of complying with the clinician’s wishes, rather than exploring and discovering their own hypnotic capacity.

Placing the hypnotic experience in the context of a test also makes it consonant with other medical examinations and procedures.⁸

Once a patient’s hypnotizability is determined, structured measurement is no longer necessary. The test-retest correlation for hypnotizability scores is 0.7 over 25 years, which is more consistent than IQ testing.⁷ Subsequent inductions usually can be generated by the patient or signaled by the clinician, and only seconds are required for the shift into trance.

Box 1

Reducing anxiety

Anxiety can be understood as a vaguely defined but immobilizing sense of distress. Lack of clarity about the discomfort’s source enhances the patient’s sense of helplessness and avoidance. One therapeutic challenge is to convert anxiety into fear—to give it a focus so that something can be done about it.

Box 2

Anxiety sets up a negative feedback cycle between psychological preoccupation and somatic discomfort, a “snowball effect” in which subjective anxiety and somatic tension reinforce each other. Hypnosis can help reduce anxiety and induce relaxation,⁹ and its dissociative component can help separate anxiety’s psychological and somatic components.

Hypnosis is as effective at reducing anxiety as 1 mg of alprazolam, at least in a study of college students.¹⁰ Student volunteers with high and low hypnotizability were given alprazolam, 1 mg, and a hypnotic suggestion based on their reactions to the drug. Four days later, when students received hypnosis only and hypnosis plus alprazolam:

• combination therapy reduced anxiety more effectively than did hypnosis or alprazolam alone, as measured by the Profile of Mood States tension-anxiety scale
• improvement was comparable with hypnosis or alprazolam alone
• highly hypnotizable students showed significantly greater relaxation than did those with low hypnotizability in all three treatment groups
• EEG data showed similar frontal and occipital changes in the alprazolam and hypnotic suggestion groups.

In randomized trials, simple self-hypnosis training has reduced pain and anxiety during medical procedures, reducing procedure time by an average 17 minutes and resulting in fewer complications.¹¹

A typical hypnotic instruction for managing anxiety is provided in Box 2. This approach teaches patients how to deal with stressors that complicate their anxiety and to control their somatic response. Hypnosis expands patients’ repertoire of responses and enables them to feel less helpless.

Confronting phobias

Phobic symptoms of fear and avoidance or exposure with distress respond especially well to brief hypnosis interventions. Although behavior modification and antidepressants also can treat phobias successfully, one or two hypnosis sessions often can reduce or cure phobic symptoms.

For example, one can help patients with airplane phobia prepare for flight by going into a hypnotic state and learning three concepts:

• Think of the airplane as an extension of the body, such as a bicycle.
• Float with the plane.
• Think about the difference between probability and possibility.

The hypnotic state—with its focused attention and physical relaxation—can amplify this cognitive restructuring technique. Phobic patients can feel more in control of their somatic reactions and, by extrapolation, the flying experience itself. In one study, 52% of patients taught this self-hypnosis exercise remained improved or cured at least 7 years later.¹²

Treating traumatic reactions

Evidence is growing that trauma elicits dissociation. Thus, hypnosis could help us understand and treat traumatic reactions, including patients with acute and posttraumatic stress disorder (PTSD) and dissociative disorders.

The hypnotic state’s controlled dissociation can be used to model the uncontrolled dissociation represented by posttraumatic phenomena such as flashbacks, numbing, and amnesia.¹³ This view is supported by evidence that PTSD is associated with high hypnotizability.^14,15

Acute stress disorder—as introduced in DSM-IV¹⁶—is characterized by prominent dissociative symptoms, with intrusion, avoidance, and hyperarousal. These diagnostic criteria recognize that acute dissociation is a common and predictable reaction to trauma.

Hypnosis involving grief work, exploration of trauma-related transference issues, and emotional expression are effective psychotherapies for persons exposed to trauma. Becoming familiar with hypnotic states can teach patients to recognize, understand, and control their dissociative states.

Evidence suggests that hypnosis’ intense concentration may reverse the dissociative mind fragmentation caused by trauma.¹⁷ Traumatic memories may seem less overwhelming and intrusive once patients discover they can:

• exert greater control over memory access and retrieval
• work through and assimilate disturbing thoughts.

The controlled experience of hypnotic abreaction (reliving traumatic and other memories with strong emotion) provides boundaries for psychotherapeutic grief work.^18,19 Instead of telling patients not to ruminate over a traumatic event, the clinician instructs the patient how to think about the experience.

The inferred message is that the patient can work on other things—such as relationships and daily living problems—after this therapeutic work is done.

Patients are slowly separated from the victim role. The goal is to help them restructure their memories, both cognitively and emotionally. They bear the memories’ impact, yet come to see the information differently.⁷ Traumatic input becomes more bearable when linked to a cognitively restructured recognition of an adaptive response.^,20 For example, patients may acknowledge what they did during a traumatic event that was self-protective or helped others.

PTSD. Hypnosis shares common elements with other cognitive and behavioral treatments for PTSD, including exposure to traumatic memories for cognitive and emotional processing. Few studies have examined using hypnosis to treat PTSD, but evidence suggests it is at least as effective as other cognitive-behavioral treatments.^20,21

Patients can be taught to view PTSD’s intrusive memories and bodily symptoms as re-experiencing painful memories. The memories often intrude less frequently after patients find a controlled method—such as self-hypnosis—to access and work them through.²²

Box 3

Self-blame. Many trauma victims would rather feel guilty than helpless. They blame themselves inappropriately for events over which they had no control, rather than accept their helplessness. They misuse hindsight about the trauma to assume the events were predictable and therefore avoidable. They imagine they can replay the events and change the outcome.

Such an approach to trauma can be profoundly demoralizing, leaving victims burdened by needless guilt and shame. Helping them face and bear the feelings associated with traumatic events can free them from efforts to “undo” or take responsibility for the trauma and accept what happened.

Split-screen technique. Using hypnosis with a “split-screen” technique can help patients restructure the memory of trauma. The left screen symbolizes the trauma in condensed form. The right screen helps patients focus on how they tried to master the situation. This grief work allows patients to acknowledge, bear, and put into perspective the humiliation of the experience and their loss of invulnerability, health, or loved ones (Box 3).¹⁸

Dissociation. Dissociating during a threatening situation may enable a person to put aside some awareness of the danger and take self-protective action. Persistent dissociation, however, may make it too easy to avoid working through the traumatic experiences later on.^22-24

Dissociation makes subsequent exposure to reminders of the trauma more similar to a reexperiencing rather than a controlled remembering of it. This can trigger physiologic stress reactions and lead to or worsen PTSD.^25-27

Dissociative disorders can be understood as chronic and severe PTSDs.²⁸ Many individuals with dissociative disorders have histories of sexual and physical abuse.^29-31 Clearly, traumatic experiences sensitize survivors to subsequent trauma through conditioned activation of fear circuitry involving the amygdala, hippocampus, and frontal lobes.³²

Hypnosis can be especially helpful—both for diagnosis and therapy.³³ It can assist the controlled recovery of memories, while allowing some images to remain dissociated from cognition until the patient is ready to deal with them. The patient can turn memories on and off by entering and exiting the hypnotic state and thereby recover and reprocess memories at a tolerable pace.

Related resources

• Society for Clinical and Experimental Hypnosis. http://ijceh.educ.wsu.edu
• American Society of Clinical Hypnosis. www.asch.net
• American Psychological Association, Division 30. Society of Psychological Hypnosis. http://www.apa.org/about/division/div30.html

Mr. M, a world-class athlete, collapsed suddenly in an alley. He was rushed to a hospital emergency room, where he nearly died of internal bleeding from a grapefruit-sized abdominal lymphoma. He was hospitalized and placed on chemotherapy.

Increasing doses of opiates hardly reduced his pain, and he became extremely anxious. Staff described him as “climbing the walls.” He lay in bed writhing, and his parents feared he was becoming a “drug addict.”

Anxiety about his life-threatening illness was clearly compounding his pain, so his attending physician ordered a psychiatric evaluation. When I interviewed the patient, I felt that hypnosis could help.

Hypnosis—as a state of highly focused attention—can help us treat patients’ anxiety, phobias, pain, posttraumatic stress disorder (PTSD), and dissociative disorders. With training, an experienced psychiatrist can quickly start using hypnosis as an adjunct to other therapies.

This article describes how hypnosis helped Mr. M and a young woman traumatized by a criminal assault. Based on my experience and the literature, I discuss what hypnosis is, what training is required, how to measure hypnotizability, and the value of hypnosis in helping patients control their anxiety, posttraumatic, and dissociative states.

Case continued: ‘Surfing’ in Hawaii

When I met Mr. M in the hospital, I acknowledged his distress and the reasons for it, saying “You don’t really want to be here, do you?”

“How many years of medical training did it take you to figure that out?” he replied.

“Well then,” I said, “let’s go somewhere else. Where would you like to be right now?”

He responded, “I’ve never surfed.”

“Good,” I replied, “let’s go to Hawaii.” In hypnosis, I had him picture himself surfing. He continued to groan, but the pattern changed. “What happened?” I asked. “I fell off the surfboard,” he replied. “OK, get back on, and do it right,” I told him.

He learned to practice self-hypnosis, which markedly reduced his anxiety and pain. Two days later he was off pain medications and joking with the nurses in the hall. The attending physician noted in the patient’s record: “Patient off pain meds. Tumor must be regressing.”

What is hypnosis?

Mr. M’s response, though unusually strong, underscores the fact that hypnosis can rapidly produce analgesia and anxiolysis in the medical setting. Hypnosis—often called “believed-in imagination”—is characterized by an ability to sustain a state of attentive, receptive, intense focal concentration with diminished peripheral awareness. The hypnotized person is awake and alert, not asleep. Hypnosis’ three main components are absorption, dissociation, and suggestibility.

Biological basis. The hypnotic state has no brain “signature” per se, but brain imaging portrays hypnosis as a state of alertness with altered anterior cingulate gyrus activation, which helps to focus attention.^1-3 Hypnotized persons can demonstrably alter blood flow in brain regions involved in perceptual processing in response to suggestions of altered perception, whether somatosensory, visual, or olfactory.^4,5 Thus, patients report not only reduced pain but changes in how they experience pain with hypnotic analgesia.

The brain’s dopamine neurotransmitter system—especially in the frontal lobes—also may be involved in hypnosis, as highly hypnotizable persons have elevated levels of dopamine metabolites in their cerebrospinal fluid.⁶

Hypnotic trance. The trance experience is often best explained to patients as similar to being absorbed in a good novel. One loses awareness of one’s surroundings and enters the imagined world. When the novel is finished, the reader requires a moment of reorientation to the surrounding world.

A trance is a state of sustained, attentive-receptive concentration in response to a signal from within or from someone else. The signal activates this shift of awareness and permits more-intensive concentration in a designated direction.

All hypnosis is self-hypnosis. Much of its clinical value is that it can be self-induced throughout the day and whenever symptoms emerge. During the first weeks, patients can be encouraged to practice every 1 or 2 hours.

Applying hypnosis to practice. A well-trained clinician can learn to use hypnosis in classes offered by the two professional hypnosis societies or the American Psychiatric Association (Box 1) Because hypnosis is not something “done to” a patient but rather a capacity to be measured, tapped, and utilized, psychiatrists can integrate hypnosis into clinical practice after some initial training, with ongoing learning and supervision.

Who can be hypnotized?

Not everyone is equally hypnotizable, and hypnotizability is a stable and measurable trait. Approximately one-quarter of adults cannot respond to hypnotic instructions, whereas 10% are extremely hypnotizable.⁷

Brief, clinically useful tests of hypnotic responsiveness have been developed, such as the Hypnotic Induction Profile (HIP).⁸ The clinician usually can induce the trance experience and systematically measure the patient’s response within 5 minutes. A HIP score of 5 indicates usable hypnotizability.

The HIP test includes instructions to produce a sense of lightness in the left arm and hand, with tests of response to this instruction. Response is characterized by dissociation, hand elevation after it is lowered, involuntariness, response to the cutoff signal, and altered sensation.

Turning hypnotic induction into a test of hypnotic capacity transforms the initial encounter by:

• removing pressure on the clinician to successfully hypnotize the subject
• reducing patients’ experiences of complying with the clinician’s wishes, rather than exploring and discovering their own hypnotic capacity.

Placing the hypnotic experience in the context of a test also makes it consonant with other medical examinations and procedures.⁸

Once a patient’s hypnotizability is determined, structured measurement is no longer necessary. The test-retest correlation for hypnotizability scores is 0.7 over 25 years, which is more consistent than IQ testing.⁷ Subsequent inductions usually can be generated by the patient or signaled by the clinician, and only seconds are required for the shift into trance.

Box 1

Reducing anxiety

Anxiety can be understood as a vaguely defined but immobilizing sense of distress. Lack of clarity about the discomfort’s source enhances the patient’s sense of helplessness and avoidance. One therapeutic challenge is to convert anxiety into fear—to give it a focus so that something can be done about it.

Box 2

Anxiety sets up a negative feedback cycle between psychological preoccupation and somatic discomfort, a “snowball effect” in which subjective anxiety and somatic tension reinforce each other. Hypnosis can help reduce anxiety and induce relaxation,⁹ and its dissociative component can help separate anxiety’s psychological and somatic components.

Hypnosis is as effective at reducing anxiety as 1 mg of alprazolam, at least in a study of college students.¹⁰ Student volunteers with high and low hypnotizability were given alprazolam, 1 mg, and a hypnotic suggestion based on their reactions to the drug. Four days later, when students received hypnosis only and hypnosis plus alprazolam:

• combination therapy reduced anxiety more effectively than did hypnosis or alprazolam alone, as measured by the Profile of Mood States tension-anxiety scale
• improvement was comparable with hypnosis or alprazolam alone
• highly hypnotizable students showed significantly greater relaxation than did those with low hypnotizability in all three treatment groups
• EEG data showed similar frontal and occipital changes in the alprazolam and hypnotic suggestion groups.

In randomized trials, simple self-hypnosis training has reduced pain and anxiety during medical procedures, reducing procedure time by an average 17 minutes and resulting in fewer complications.¹¹

A typical hypnotic instruction for managing anxiety is provided in Box 2. This approach teaches patients how to deal with stressors that complicate their anxiety and to control their somatic response. Hypnosis expands patients’ repertoire of responses and enables them to feel less helpless.

Confronting phobias

Phobic symptoms of fear and avoidance or exposure with distress respond especially well to brief hypnosis interventions. Although behavior modification and antidepressants also can treat phobias successfully, one or two hypnosis sessions often can reduce or cure phobic symptoms.

For example, one can help patients with airplane phobia prepare for flight by going into a hypnotic state and learning three concepts:

• Think of the airplane as an extension of the body, such as a bicycle.
• Float with the plane.
• Think about the difference between probability and possibility.

The hypnotic state—with its focused attention and physical relaxation—can amplify this cognitive restructuring technique. Phobic patients can feel more in control of their somatic reactions and, by extrapolation, the flying experience itself. In one study, 52% of patients taught this self-hypnosis exercise remained improved or cured at least 7 years later.¹²

Treating traumatic reactions

Evidence is growing that trauma elicits dissociation. Thus, hypnosis could help us understand and treat traumatic reactions, including patients with acute and posttraumatic stress disorder (PTSD) and dissociative disorders.

The hypnotic state’s controlled dissociation can be used to model the uncontrolled dissociation represented by posttraumatic phenomena such as flashbacks, numbing, and amnesia.¹³ This view is supported by evidence that PTSD is associated with high hypnotizability.^14,15

Acute stress disorder—as introduced in DSM-IV¹⁶—is characterized by prominent dissociative symptoms, with intrusion, avoidance, and hyperarousal. These diagnostic criteria recognize that acute dissociation is a common and predictable reaction to trauma.

Hypnosis involving grief work, exploration of trauma-related transference issues, and emotional expression are effective psychotherapies for persons exposed to trauma. Becoming familiar with hypnotic states can teach patients to recognize, understand, and control their dissociative states.

Evidence suggests that hypnosis’ intense concentration may reverse the dissociative mind fragmentation caused by trauma.¹⁷ Traumatic memories may seem less overwhelming and intrusive once patients discover they can:

• exert greater control over memory access and retrieval
• work through and assimilate disturbing thoughts.

The controlled experience of hypnotic abreaction (reliving traumatic and other memories with strong emotion) provides boundaries for psychotherapeutic grief work.^18,19 Instead of telling patients not to ruminate over a traumatic event, the clinician instructs the patient how to think about the experience.

The inferred message is that the patient can work on other things—such as relationships and daily living problems—after this therapeutic work is done.

Patients are slowly separated from the victim role. The goal is to help them restructure their memories, both cognitively and emotionally. They bear the memories’ impact, yet come to see the information differently.⁷ Traumatic input becomes more bearable when linked to a cognitively restructured recognition of an adaptive response.^,20 For example, patients may acknowledge what they did during a traumatic event that was self-protective or helped others.

PTSD. Hypnosis shares common elements with other cognitive and behavioral treatments for PTSD, including exposure to traumatic memories for cognitive and emotional processing. Few studies have examined using hypnosis to treat PTSD, but evidence suggests it is at least as effective as other cognitive-behavioral treatments.^20,21

Patients can be taught to view PTSD’s intrusive memories and bodily symptoms as re-experiencing painful memories. The memories often intrude less frequently after patients find a controlled method—such as self-hypnosis—to access and work them through.²²

Box 3

Self-blame. Many trauma victims would rather feel guilty than helpless. They blame themselves inappropriately for events over which they had no control, rather than accept their helplessness. They misuse hindsight about the trauma to assume the events were predictable and therefore avoidable. They imagine they can replay the events and change the outcome.

Such an approach to trauma can be profoundly demoralizing, leaving victims burdened by needless guilt and shame. Helping them face and bear the feelings associated with traumatic events can free them from efforts to “undo” or take responsibility for the trauma and accept what happened.

Split-screen technique. Using hypnosis with a “split-screen” technique can help patients restructure the memory of trauma. The left screen symbolizes the trauma in condensed form. The right screen helps patients focus on how they tried to master the situation. This grief work allows patients to acknowledge, bear, and put into perspective the humiliation of the experience and their loss of invulnerability, health, or loved ones (Box 3).¹⁸

Dissociation. Dissociating during a threatening situation may enable a person to put aside some awareness of the danger and take self-protective action. Persistent dissociation, however, may make it too easy to avoid working through the traumatic experiences later on.^22-24

Dissociation makes subsequent exposure to reminders of the trauma more similar to a reexperiencing rather than a controlled remembering of it. This can trigger physiologic stress reactions and lead to or worsen PTSD.^25-27

Dissociative disorders can be understood as chronic and severe PTSDs.²⁸ Many individuals with dissociative disorders have histories of sexual and physical abuse.^29-31 Clearly, traumatic experiences sensitize survivors to subsequent trauma through conditioned activation of fear circuitry involving the amygdala, hippocampus, and frontal lobes.³²

Hypnosis can be especially helpful—both for diagnosis and therapy.³³ It can assist the controlled recovery of memories, while allowing some images to remain dissociated from cognition until the patient is ready to deal with them. The patient can turn memories on and off by entering and exiting the hypnotic state and thereby recover and reprocess memories at a tolerable pace.

Related resources

• Society for Clinical and Experimental Hypnosis. http://ijceh.educ.wsu.edu
• American Society of Clinical Hypnosis. www.asch.net
• American Psychological Association, Division 30. Society of Psychological Hypnosis. http://www.apa.org/about/division/div30.html

Families and schools often pressure clinicians to “do something” when children or adolescents persistently bully, threaten, or injure others. This demand poses a treatment dilemma when psychosocial and educational interventions have failed to manage pediatric aggression.

Aggression is the main reason for drug therapy in youths with conduct disorder, but very little safety and efficacy data exist to help us choose medications. This places young patients at risk for polypharmacy, unmanaged symptoms, short-term side effects, and unknown long-term consequences of exposure to psychotropics.

Table 1

4 precautions when prescribing for pediatric aggression

This article reviews the limited data on using medications to reduce aggression in children and adolescents, focusing on double-blind, placebo-controlled trials in conduct disorder. Based on this evidence and our clinical experience, we offer a sample case and treatment recommendations.

Prescribing principles

Precautions. When prescribing drugs to treat aggressive youth, remember the American Academy of Child and Adolescent Psychiatry’s precautions (Table 1)¹ Recently published recommendations prepared by expert consensus are also valuable treatment guides.²

Linking treatment to diagnosis. Should we attempt to manage aggression as a manifestation of an underlying psychiatric disorder? Or should we treat it the same across all disorders? The latter approach is akin to the “fever model.”

Fever—regardless of cause—may be treated with a nonsteroidal anti-inflammatory drug. However, evidence from drug studies suggests that underlying psychiatric disorders should help determine the choice of aggression treatment. For example, a recent study in adults found that divalproex was effective for aggressive patients only within a specific diagnostic subgroup (in this case, cluster B personality disorders).³

Clinical experience also links aggression treatment with underlying diagnoses. For example, aggression secondary to agitated depression is treated with an antidepressant, whereas aggression secondary to command hallucinations in schizophrenia is treated with antipsychotics.

In treating aggression in conduct disorder (Table 2), first treat comorbid disorders—such as attention deficit/hyperactivity disorder (ADHD) or bipolar disorder—and address the child’s psychosocial and educational needs. Then if medication is appropriate, consider drugs with evidence of safety and efficacy, such as antipsychotics, lithium, and stimulants.

Antipsychotics

Three conventional antipsychotics—chlorpromazine, haloperidol, and thioridazine—are FDA-approved for controlling disruptive behaviors in children.⁴ No atypical antipsychotics are so indicated, but atypicals are preferred in children and adolescents because of lower risks for tardive dyskinesia, neuroleptic malignant syndrome, and extrapyramidal symptoms.²

Risperidone is the most-studied atypical antipsychotic for treating pediatric aggression, particularly in patients with low intellectual functioning or mental retardation. In a 6-week, double-blind, placebo-controlled trial, 118 children ages 5 to 12 with severely disruptive behavior and IQs of 36 to 84 were given low-dose risperidone (mean 1.16 mg/d). Risperidone reduced conduct problems significantly more than placebo, although aggression was not measured directly.⁵ Adverse events included somnolence, headache, vomiting, weight gain, and elevated serum prolactin. Similar results have been reported in other studies.⁶

Table 2

Diagnostic criteria for conduct disorder

Box 1

Risperidone also reduced aggression in children with normal intelligence in one small study.⁷ As a cautionary note, however, long-term risperidone treatment has been associated with withdrawal dyskinesias.⁸

Olanzapine, quetiapine, ziprasidone, and aripiprazole are less well-studied for treating pediatric aggression but are preferable to conventional agents when antipsychotics are considered.

Recommendation. Expert consensus opinion² recommends using atypicals when psychosocial treatments and first-line medications for primary conditions have failed. Start with low dosages, and titrate up slowly while monitoring symptoms and side effects. Because no studies have compared any atypical’s efficacy over others for aggressive behavior, base your choices on:

• discussions with the patient and family (Box 1)
• medical comorbidities
• how the patient responded to antipsychotics in the past
• side-effect profile
• long-term treatment planning.²

If the patient cannot tolerate the medication or does not respond after 4 to 6 weeks, try switching atypicals. To improve partial response, consider adding a mood stabilizer such as lithium or divalproex. If aggressive symptoms remit for 6 months or longer, attempt to taper or discontinue the antipsychotic.²

Lithium

In placebo-controlled trials, lithium reduced aggression in:

• male prisoners ages 16 to 24.⁹
• children ages 7 and 12 with conduct disorder¹⁰
• children and adolescents ages 10 to 17 with conduct disorder.¹¹

Among these studies, only ours¹¹ specifically measured aggression. We randomly assigned 40 children to receive 4 weeks of lithium, 900 to 2,100 mg/d (mean 1,425 ± 321 mg/d), or placebo. Serum lithium levels were 0.78 to 1.55 mEq/L (mean 1.07 ± 0.19 mEq/L). We used the Overt Aggression Scale (OAS)^12,13 (see Related resources) to track frequency and severity of verbal aggression, aggression against objects, aggression against others, and self-aggression.

Lithium reduced aggression more than did placebo, as measured by the clinician-rated Clinical Global Impressions (CGI) scale and staff-rated Global Clinical Judgments (Consensus) Scale (GCJCS). The CGI showed a 70% response rate with lithium and 20% with placebo. Similarly, the GCJCS scale showed 80% response with lithium and 30% with placebo.

The aggression reduction with lithium was statistically significant and clinically evident. Most subjects (37 of 40) experienced at least one adverse event, however, whether receiving lithium or placebo. Nausea, vomiting, and urinary frequency were significantly more common in the lithium-treated group than with placebo. Fewer adverse events were reported in a similar outpatient study,¹⁴ probably because of less-frequent monitoring.

Lithium did not reduce aggression in adolescent girls treated for 2 weeks¹⁵ or in an outpatient study of children with ADHD.¹⁶

Recommendation. Lithium has shown efficacy for reducing severe aggression in hospitalized children with conduct disorder but not in similar outpatients. Consider this drug to reduce severe aggression in children with conduct disorder, especially if they have failed other treatments.

Anticonvulsants

Anticonvulsants have been used to decrease aggression for more than 50 years, and epidemiologic data show their use is increasing markedly.¹⁷ Few controlled studies support this prescribing trend, however.¹⁸

Initial reports suggested that anticonvulsants reduce disruptive behaviors, but more-critically designed studies have not supported this finding. For example, phenytoin sodium (diphenylhydantoin) demonstrated efficacy in open trials, but controlled trials found this anticonvulsant no more effective than placebo. In fact, placebo may have reduced aggression more than the active drug. Likewise, earlier controlled trials of carbamazepine indicated efficacy, but more-carefully designed trials using specific measures of aggression did not.

Divalproex is the anticonvulsant most commonly used for aggression in children and adolescents. Only one small, placebo-controlled study has found it effective in reducing aggression in children.¹⁹

Twenty children ages 10 to 18 with conduct disorder or oppositional defiant disorder were randomized to divalproex, 750 to 1,500 mg/d, or placebo. Eighteen completed the first phase, and 15 crossed over to the other treatment. Concomitant drug treatment, including stimulants, was allowed. The authors reported that 12 of 15 subjects showed some response to divalproex.

A 7-week study compared divalproex in high dosages (up to 1,500 mg/d) versus low dosages (up to 250 mg/d). This study was not placebo-controlled, but aggression was reduced more in the high-dosage than in the low-dosage group.²⁰

Recommendation. If you use an anticonvulsant, first obtain informed consent from the patient and parent. Divalproex causes weight gain and has been associated with increased risk of polycystic ovary syndrome with masculinizing effects.²¹

Double-blind, placebo-controlled studies of divalproex and other anticonvulsants in treating aggression are needed, particularly as prescriptions for these agents are rising.

Stimulants

Some small controlled studies suggest that stimulants can reduce aggression in children with ADHD, but their effects on aggression in conduct disorder have not been well studied. Aggression was not measured directly in the National Institute of Mental Health Multimodal Treatment Study of Children with ADHD.²¹ Most other studies have been small and included children with ADHD but not necessarily conduct disorder.

Recommendation. Stimulants may help reduce aggression in children with ADHD, but studies gauging their effects in conduct disorder are needed.

Alpha agonists

Alpha agonists such as clonidine and guanfacine are increasingly being used to treat children with disruptive disorders, despite limited evidence. The small controlled studies that examined alpha agonists as monotherapy or add-ons in this population did not directly measure aggression.^22,23

Recommendation. Little data support alpha agonists for reducing aggression. They should probably be considered second-line treatment.

SSRIs

No double-blind, placebo-controlled studies have tested any selective serotonin reuptake inhibitor (SSRIs) for reducing aggression in conduct disorder. In a 6-week open study, citalopram (mean 27 mg/d) reduced impulsive aggression in 12 children with mixed diagnoses, as measured by the modified OAS,¹³ Child Behavior Checklist, and CGI.²⁴

Recommendation. Use caution when prescribing SSRIs to aggressive youth, as these drugs may contribute to aggression in some mood-disordered children. More evidence of SSRIs’ safety and efficacy in this population is needed.

Related resources

• Overt Aggression Scale. In: Coccaro EF, Harvey PD, Kupsaw-Lawrence E, et al. Development of neuropharmacologically-based behavioral assessments of impulsiveaggressive behavior. J Neuropsychiatry 1991;3(2):S44-S51.

Drug brand names

• Aripiprazole • Abilify
• Carbamazepine • Tegretol
• Citalopram • Celexa
• Chlorpromazine • Thorazine
• Clonidine • Catapres
• Phenytoin sodium • Dilantin
• Divalproex • Depakote
• Guanfacine • Tenex
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Thioridazine • Mellaril
• Ziprasidone • Geodon

Disclosure

Dr. Malone receives research support from Pfizer Inc. and Eli Lilly and Co. and is a consultant to Janssen Pharmaceutica.

Dr. Delaney is a consultant to Shire Pharmaceuticals.

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

Families and schools often pressure clinicians to “do something” when children or adolescents persistently bully, threaten, or injure others. This demand poses a treatment dilemma when psychosocial and educational interventions have failed to manage pediatric aggression.

Aggression is the main reason for drug therapy in youths with conduct disorder, but very little safety and efficacy data exist to help us choose medications. This places young patients at risk for polypharmacy, unmanaged symptoms, short-term side effects, and unknown long-term consequences of exposure to psychotropics.

Table 1

4 precautions when prescribing for pediatric aggression

This article reviews the limited data on using medications to reduce aggression in children and adolescents, focusing on double-blind, placebo-controlled trials in conduct disorder. Based on this evidence and our clinical experience, we offer a sample case and treatment recommendations.

Prescribing principles

Precautions. When prescribing drugs to treat aggressive youth, remember the American Academy of Child and Adolescent Psychiatry’s precautions (Table 1)¹ Recently published recommendations prepared by expert consensus are also valuable treatment guides.²

Linking treatment to diagnosis. Should we attempt to manage aggression as a manifestation of an underlying psychiatric disorder? Or should we treat it the same across all disorders? The latter approach is akin to the “fever model.”

Fever—regardless of cause—may be treated with a nonsteroidal anti-inflammatory drug. However, evidence from drug studies suggests that underlying psychiatric disorders should help determine the choice of aggression treatment. For example, a recent study in adults found that divalproex was effective for aggressive patients only within a specific diagnostic subgroup (in this case, cluster B personality disorders).³

Clinical experience also links aggression treatment with underlying diagnoses. For example, aggression secondary to agitated depression is treated with an antidepressant, whereas aggression secondary to command hallucinations in schizophrenia is treated with antipsychotics.

In treating aggression in conduct disorder (Table 2), first treat comorbid disorders—such as attention deficit/hyperactivity disorder (ADHD) or bipolar disorder—and address the child’s psychosocial and educational needs. Then if medication is appropriate, consider drugs with evidence of safety and efficacy, such as antipsychotics, lithium, and stimulants.

Antipsychotics

Three conventional antipsychotics—chlorpromazine, haloperidol, and thioridazine—are FDA-approved for controlling disruptive behaviors in children.⁴ No atypical antipsychotics are so indicated, but atypicals are preferred in children and adolescents because of lower risks for tardive dyskinesia, neuroleptic malignant syndrome, and extrapyramidal symptoms.²

Risperidone is the most-studied atypical antipsychotic for treating pediatric aggression, particularly in patients with low intellectual functioning or mental retardation. In a 6-week, double-blind, placebo-controlled trial, 118 children ages 5 to 12 with severely disruptive behavior and IQs of 36 to 84 were given low-dose risperidone (mean 1.16 mg/d). Risperidone reduced conduct problems significantly more than placebo, although aggression was not measured directly.⁵ Adverse events included somnolence, headache, vomiting, weight gain, and elevated serum prolactin. Similar results have been reported in other studies.⁶

Table 2

Diagnostic criteria for conduct disorder

Box 1

Risperidone also reduced aggression in children with normal intelligence in one small study.⁷ As a cautionary note, however, long-term risperidone treatment has been associated with withdrawal dyskinesias.⁸

Olanzapine, quetiapine, ziprasidone, and aripiprazole are less well-studied for treating pediatric aggression but are preferable to conventional agents when antipsychotics are considered.

Recommendation. Expert consensus opinion² recommends using atypicals when psychosocial treatments and first-line medications for primary conditions have failed. Start with low dosages, and titrate up slowly while monitoring symptoms and side effects. Because no studies have compared any atypical’s efficacy over others for aggressive behavior, base your choices on:

• discussions with the patient and family (Box 1)
• medical comorbidities
• how the patient responded to antipsychotics in the past
• side-effect profile
• long-term treatment planning.²

If the patient cannot tolerate the medication or does not respond after 4 to 6 weeks, try switching atypicals. To improve partial response, consider adding a mood stabilizer such as lithium or divalproex. If aggressive symptoms remit for 6 months or longer, attempt to taper or discontinue the antipsychotic.²

Lithium

In placebo-controlled trials, lithium reduced aggression in:

• male prisoners ages 16 to 24.⁹
• children ages 7 and 12 with conduct disorder¹⁰
• children and adolescents ages 10 to 17 with conduct disorder.¹¹

Among these studies, only ours¹¹ specifically measured aggression. We randomly assigned 40 children to receive 4 weeks of lithium, 900 to 2,100 mg/d (mean 1,425 ± 321 mg/d), or placebo. Serum lithium levels were 0.78 to 1.55 mEq/L (mean 1.07 ± 0.19 mEq/L). We used the Overt Aggression Scale (OAS)^12,13 (see Related resources) to track frequency and severity of verbal aggression, aggression against objects, aggression against others, and self-aggression.

Lithium reduced aggression more than did placebo, as measured by the clinician-rated Clinical Global Impressions (CGI) scale and staff-rated Global Clinical Judgments (Consensus) Scale (GCJCS). The CGI showed a 70% response rate with lithium and 20% with placebo. Similarly, the GCJCS scale showed 80% response with lithium and 30% with placebo.

The aggression reduction with lithium was statistically significant and clinically evident. Most subjects (37 of 40) experienced at least one adverse event, however, whether receiving lithium or placebo. Nausea, vomiting, and urinary frequency were significantly more common in the lithium-treated group than with placebo. Fewer adverse events were reported in a similar outpatient study,¹⁴ probably because of less-frequent monitoring.

Lithium did not reduce aggression in adolescent girls treated for 2 weeks¹⁵ or in an outpatient study of children with ADHD.¹⁶

Recommendation. Lithium has shown efficacy for reducing severe aggression in hospitalized children with conduct disorder but not in similar outpatients. Consider this drug to reduce severe aggression in children with conduct disorder, especially if they have failed other treatments.

Anticonvulsants

Anticonvulsants have been used to decrease aggression for more than 50 years, and epidemiologic data show their use is increasing markedly.¹⁷ Few controlled studies support this prescribing trend, however.¹⁸

Initial reports suggested that anticonvulsants reduce disruptive behaviors, but more-critically designed studies have not supported this finding. For example, phenytoin sodium (diphenylhydantoin) demonstrated efficacy in open trials, but controlled trials found this anticonvulsant no more effective than placebo. In fact, placebo may have reduced aggression more than the active drug. Likewise, earlier controlled trials of carbamazepine indicated efficacy, but more-carefully designed trials using specific measures of aggression did not.

Divalproex is the anticonvulsant most commonly used for aggression in children and adolescents. Only one small, placebo-controlled study has found it effective in reducing aggression in children.¹⁹

Twenty children ages 10 to 18 with conduct disorder or oppositional defiant disorder were randomized to divalproex, 750 to 1,500 mg/d, or placebo. Eighteen completed the first phase, and 15 crossed over to the other treatment. Concomitant drug treatment, including stimulants, was allowed. The authors reported that 12 of 15 subjects showed some response to divalproex.

A 7-week study compared divalproex in high dosages (up to 1,500 mg/d) versus low dosages (up to 250 mg/d). This study was not placebo-controlled, but aggression was reduced more in the high-dosage than in the low-dosage group.²⁰

Recommendation. If you use an anticonvulsant, first obtain informed consent from the patient and parent. Divalproex causes weight gain and has been associated with increased risk of polycystic ovary syndrome with masculinizing effects.²¹

Double-blind, placebo-controlled studies of divalproex and other anticonvulsants in treating aggression are needed, particularly as prescriptions for these agents are rising.

Stimulants

Some small controlled studies suggest that stimulants can reduce aggression in children with ADHD, but their effects on aggression in conduct disorder have not been well studied. Aggression was not measured directly in the National Institute of Mental Health Multimodal Treatment Study of Children with ADHD.²¹ Most other studies have been small and included children with ADHD but not necessarily conduct disorder.

Recommendation. Stimulants may help reduce aggression in children with ADHD, but studies gauging their effects in conduct disorder are needed.

Alpha agonists

Alpha agonists such as clonidine and guanfacine are increasingly being used to treat children with disruptive disorders, despite limited evidence. The small controlled studies that examined alpha agonists as monotherapy or add-ons in this population did not directly measure aggression.^22,23

Recommendation. Little data support alpha agonists for reducing aggression. They should probably be considered second-line treatment.

SSRIs

No double-blind, placebo-controlled studies have tested any selective serotonin reuptake inhibitor (SSRIs) for reducing aggression in conduct disorder. In a 6-week open study, citalopram (mean 27 mg/d) reduced impulsive aggression in 12 children with mixed diagnoses, as measured by the modified OAS,¹³ Child Behavior Checklist, and CGI.²⁴

Recommendation. Use caution when prescribing SSRIs to aggressive youth, as these drugs may contribute to aggression in some mood-disordered children. More evidence of SSRIs’ safety and efficacy in this population is needed.

Related resources

• Overt Aggression Scale. In: Coccaro EF, Harvey PD, Kupsaw-Lawrence E, et al. Development of neuropharmacologically-based behavioral assessments of impulsiveaggressive behavior. J Neuropsychiatry 1991;3(2):S44-S51.

Drug brand names

• Aripiprazole • Abilify
• Carbamazepine • Tegretol
• Citalopram • Celexa
• Chlorpromazine • Thorazine
• Clonidine • Catapres
• Phenytoin sodium • Dilantin
• Divalproex • Depakote
• Guanfacine • Tenex
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Thioridazine • Mellaril
• Ziprasidone • Geodon

Disclosure

Dr. Malone receives research support from Pfizer Inc. and Eli Lilly and Co. and is a consultant to Janssen Pharmaceutica.

Dr. Delaney is a consultant to Shire Pharmaceuticals.

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

Families and schools often pressure clinicians to “do something” when children or adolescents persistently bully, threaten, or injure others. This demand poses a treatment dilemma when psychosocial and educational interventions have failed to manage pediatric aggression.

Aggression is the main reason for drug therapy in youths with conduct disorder, but very little safety and efficacy data exist to help us choose medications. This places young patients at risk for polypharmacy, unmanaged symptoms, short-term side effects, and unknown long-term consequences of exposure to psychotropics.

Table 1

4 precautions when prescribing for pediatric aggression

This article reviews the limited data on using medications to reduce aggression in children and adolescents, focusing on double-blind, placebo-controlled trials in conduct disorder. Based on this evidence and our clinical experience, we offer a sample case and treatment recommendations.

Prescribing principles

Precautions. When prescribing drugs to treat aggressive youth, remember the American Academy of Child and Adolescent Psychiatry’s precautions (Table 1)¹ Recently published recommendations prepared by expert consensus are also valuable treatment guides.²

Linking treatment to diagnosis. Should we attempt to manage aggression as a manifestation of an underlying psychiatric disorder? Or should we treat it the same across all disorders? The latter approach is akin to the “fever model.”

Fever—regardless of cause—may be treated with a nonsteroidal anti-inflammatory drug. However, evidence from drug studies suggests that underlying psychiatric disorders should help determine the choice of aggression treatment. For example, a recent study in adults found that divalproex was effective for aggressive patients only within a specific diagnostic subgroup (in this case, cluster B personality disorders).³

Clinical experience also links aggression treatment with underlying diagnoses. For example, aggression secondary to agitated depression is treated with an antidepressant, whereas aggression secondary to command hallucinations in schizophrenia is treated with antipsychotics.

In treating aggression in conduct disorder (Table 2), first treat comorbid disorders—such as attention deficit/hyperactivity disorder (ADHD) or bipolar disorder—and address the child’s psychosocial and educational needs. Then if medication is appropriate, consider drugs with evidence of safety and efficacy, such as antipsychotics, lithium, and stimulants.

Antipsychotics

Three conventional antipsychotics—chlorpromazine, haloperidol, and thioridazine—are FDA-approved for controlling disruptive behaviors in children.⁴ No atypical antipsychotics are so indicated, but atypicals are preferred in children and adolescents because of lower risks for tardive dyskinesia, neuroleptic malignant syndrome, and extrapyramidal symptoms.²

Risperidone is the most-studied atypical antipsychotic for treating pediatric aggression, particularly in patients with low intellectual functioning or mental retardation. In a 6-week, double-blind, placebo-controlled trial, 118 children ages 5 to 12 with severely disruptive behavior and IQs of 36 to 84 were given low-dose risperidone (mean 1.16 mg/d). Risperidone reduced conduct problems significantly more than placebo, although aggression was not measured directly.⁵ Adverse events included somnolence, headache, vomiting, weight gain, and elevated serum prolactin. Similar results have been reported in other studies.⁶

Table 2

Diagnostic criteria for conduct disorder

Box 1

Risperidone also reduced aggression in children with normal intelligence in one small study.⁷ As a cautionary note, however, long-term risperidone treatment has been associated with withdrawal dyskinesias.⁸

Olanzapine, quetiapine, ziprasidone, and aripiprazole are less well-studied for treating pediatric aggression but are preferable to conventional agents when antipsychotics are considered.

Recommendation. Expert consensus opinion² recommends using atypicals when psychosocial treatments and first-line medications for primary conditions have failed. Start with low dosages, and titrate up slowly while monitoring symptoms and side effects. Because no studies have compared any atypical’s efficacy over others for aggressive behavior, base your choices on:

• discussions with the patient and family (Box 1)
• medical comorbidities
• how the patient responded to antipsychotics in the past
• side-effect profile
• long-term treatment planning.²

If the patient cannot tolerate the medication or does not respond after 4 to 6 weeks, try switching atypicals. To improve partial response, consider adding a mood stabilizer such as lithium or divalproex. If aggressive symptoms remit for 6 months or longer, attempt to taper or discontinue the antipsychotic.²

Lithium

In placebo-controlled trials, lithium reduced aggression in:

• male prisoners ages 16 to 24.⁹
• children ages 7 and 12 with conduct disorder¹⁰
• children and adolescents ages 10 to 17 with conduct disorder.¹¹

Among these studies, only ours¹¹ specifically measured aggression. We randomly assigned 40 children to receive 4 weeks of lithium, 900 to 2,100 mg/d (mean 1,425 ± 321 mg/d), or placebo. Serum lithium levels were 0.78 to 1.55 mEq/L (mean 1.07 ± 0.19 mEq/L). We used the Overt Aggression Scale (OAS)^12,13 (see Related resources) to track frequency and severity of verbal aggression, aggression against objects, aggression against others, and self-aggression.

Lithium reduced aggression more than did placebo, as measured by the clinician-rated Clinical Global Impressions (CGI) scale and staff-rated Global Clinical Judgments (Consensus) Scale (GCJCS). The CGI showed a 70% response rate with lithium and 20% with placebo. Similarly, the GCJCS scale showed 80% response with lithium and 30% with placebo.

The aggression reduction with lithium was statistically significant and clinically evident. Most subjects (37 of 40) experienced at least one adverse event, however, whether receiving lithium or placebo. Nausea, vomiting, and urinary frequency were significantly more common in the lithium-treated group than with placebo. Fewer adverse events were reported in a similar outpatient study,¹⁴ probably because of less-frequent monitoring.

Lithium did not reduce aggression in adolescent girls treated for 2 weeks¹⁵ or in an outpatient study of children with ADHD.¹⁶

Recommendation. Lithium has shown efficacy for reducing severe aggression in hospitalized children with conduct disorder but not in similar outpatients. Consider this drug to reduce severe aggression in children with conduct disorder, especially if they have failed other treatments.

Anticonvulsants

Anticonvulsants have been used to decrease aggression for more than 50 years, and epidemiologic data show their use is increasing markedly.¹⁷ Few controlled studies support this prescribing trend, however.¹⁸

Initial reports suggested that anticonvulsants reduce disruptive behaviors, but more-critically designed studies have not supported this finding. For example, phenytoin sodium (diphenylhydantoin) demonstrated efficacy in open trials, but controlled trials found this anticonvulsant no more effective than placebo. In fact, placebo may have reduced aggression more than the active drug. Likewise, earlier controlled trials of carbamazepine indicated efficacy, but more-carefully designed trials using specific measures of aggression did not.

Divalproex is the anticonvulsant most commonly used for aggression in children and adolescents. Only one small, placebo-controlled study has found it effective in reducing aggression in children.¹⁹

Twenty children ages 10 to 18 with conduct disorder or oppositional defiant disorder were randomized to divalproex, 750 to 1,500 mg/d, or placebo. Eighteen completed the first phase, and 15 crossed over to the other treatment. Concomitant drug treatment, including stimulants, was allowed. The authors reported that 12 of 15 subjects showed some response to divalproex.

A 7-week study compared divalproex in high dosages (up to 1,500 mg/d) versus low dosages (up to 250 mg/d). This study was not placebo-controlled, but aggression was reduced more in the high-dosage than in the low-dosage group.²⁰

Recommendation. If you use an anticonvulsant, first obtain informed consent from the patient and parent. Divalproex causes weight gain and has been associated with increased risk of polycystic ovary syndrome with masculinizing effects.²¹

Double-blind, placebo-controlled studies of divalproex and other anticonvulsants in treating aggression are needed, particularly as prescriptions for these agents are rising.

Stimulants

Some small controlled studies suggest that stimulants can reduce aggression in children with ADHD, but their effects on aggression in conduct disorder have not been well studied. Aggression was not measured directly in the National Institute of Mental Health Multimodal Treatment Study of Children with ADHD.²¹ Most other studies have been small and included children with ADHD but not necessarily conduct disorder.

Recommendation. Stimulants may help reduce aggression in children with ADHD, but studies gauging their effects in conduct disorder are needed.

Alpha agonists

Alpha agonists such as clonidine and guanfacine are increasingly being used to treat children with disruptive disorders, despite limited evidence. The small controlled studies that examined alpha agonists as monotherapy or add-ons in this population did not directly measure aggression.^22,23

Recommendation. Little data support alpha agonists for reducing aggression. They should probably be considered second-line treatment.

SSRIs

No double-blind, placebo-controlled studies have tested any selective serotonin reuptake inhibitor (SSRIs) for reducing aggression in conduct disorder. In a 6-week open study, citalopram (mean 27 mg/d) reduced impulsive aggression in 12 children with mixed diagnoses, as measured by the modified OAS,¹³ Child Behavior Checklist, and CGI.²⁴

Recommendation. Use caution when prescribing SSRIs to aggressive youth, as these drugs may contribute to aggression in some mood-disordered children. More evidence of SSRIs’ safety and efficacy in this population is needed.

Related resources

• Overt Aggression Scale. In: Coccaro EF, Harvey PD, Kupsaw-Lawrence E, et al. Development of neuropharmacologically-based behavioral assessments of impulsiveaggressive behavior. J Neuropsychiatry 1991;3(2):S44-S51.

Drug brand names

• Aripiprazole • Abilify
• Carbamazepine • Tegretol
• Citalopram • Celexa
• Chlorpromazine • Thorazine
• Clonidine • Catapres
• Phenytoin sodium • Dilantin
• Divalproex • Depakote
• Guanfacine • Tenex
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Thioridazine • Mellaril
• Ziprasidone • Geodon

Disclosure

Dr. Malone receives research support from Pfizer Inc. and Eli Lilly and Co. and is a consultant to Janssen Pharmaceutica.

Dr. Delaney is a consultant to Shire Pharmaceuticals.

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

Because no one treatment fits all patients with binge eating disorder, their management usually requires an individualized program of:

• behavioral weight control
• psychotherapy
• and sometimes medications.

In our weight management clinic, we consider medication options based on patient preference and whether BED is uncomplicated (Figure 1) or coexists with a mood disorder (Figure 2).

This article presents the evidence on which we base our comprehensive approach. General psychiatrists with knowledge of BED can treat patients with this eating disorder, although complicated cases may require referral for specialized treatment.

Figure 1 Medication options for uncomplicated BED

Clinical characteristics

Psychiatric comorbidity. BED often occurs in patients with mood, anxiety, substance-abuse, impulsecontrol, and personality disorders.^4,6,10-12 Mood disorder—particularly depression—appears to be the most common comorbidity. BED can occur with bipolar disorder¹²—a comorbidity that in our experience is underrecognized both clinically and in the literature.

Patients with BED and bipolar disorder show increased impulsivity and mood lability. As bipolar II disorder and other “soft-spectrum” forms are more common than bipolar I disorder, BED is also more likely to occur with hypomania than mania.

Overweight. Not surprisingly, BED is associated with overweight and obesity.^5,8,9,11 Not all patients with BED are overweight or obese, but most who participate in clinical trials of BED treatments are at least overweight. BED has been reported in up to:

• 30% of participants in weight-loss programs⁷
• 70% of participants in groups such as Overeaters Anonymous
• 50% of patients who seek bariatric surgery.⁵

In our experience, patients are often more distressed by their weight than by their binge eating, depression, or anxiety. Indeed, overweight and obesity are the usual reasons patients with BED present for treatment at our center.

Diagnosis. BED’s validity as a clinical diagnosis has been controversial since the disorder was first included in DSM-IV (Table 1).³ Debate continues about some definitions in the DSM criteria, including what amount of food is “definitely larger” than most people would eat and what is “loss of control over eating.”

Nevertheless, screening for BED is relatively easy. Clinicians may use the eating disorder section of the Structured Clinical Interview for DSM-IV or the Eating Disorders Examination. Alternatively, simply ask patients if they have episodes of uncontrollable overeating, during which they eat unusually large amounts of food and their eating feels out of control.

Course. BED begins in adolescence or adulthood. Disease course is variable, with periods of remission, recurrence, and chronicity.^6,7,10 Interestingly, one prospective study showed that even if the binge eating resolves, persons may still develop obesity.¹³

Prevalence. BED affects 1.5% to 3% of the U.S. population. It is more common in women than men, equally prevalent in whites and blacks, and more prevalent than anorexia nervosa and bulimia nervosa combined.^11,14 Subthreshold BED—such as obesity with infrequent or nondistressing binge eating—appears to be much more common,¹⁰ although no data are available.

Theories of binge eating

BED’s cause is unknown, but biological, familial, and psychosocial factors have been implicated.

Biological factors. The neurotransmitters serotonin (5-HT) and dopamine—as well as various peptides—have been shown to help regulate feeding behavior.¹⁰

Table 1

Diagnostic criteria for binge-eating disorder*

Serotonin. Reduced 5-HT transporter binding has been shown in obese women with BED.¹⁵ Their 5-HT binding improved and binge eating subsided with group psychotherapy and fluoxetine, although the women continued to gain weight.

Figure 2 Medication options for BED with obesity and a mood disorder*

Genetic factors. In severely obese patients (body mass index 44±2), those with a DSM-IV diagnosis of BED exhibited mutations of the melanocortin 4 receptor gene, which affects the anorectic properties of alpha melanocyte-stimulating hormone.¹⁷

Familial factors associated with BED include parental depression and obesity.¹⁸

Psychosocial correlates include physical and sexual abuse, bullying by peers, and discrimination because of being overweight.¹⁹

Treatment recommendations

Few systematic studies have examined BED treatment. Emerging research suggests that behavioral weight-loss treatment, specialized psychotherapies, and medications may be effective in some patients with BED.^4,6,8

Behavioral weight-loss treatment’s main goal is to manage the patient’s weight with a lower-calorie, healthy diet and to increase exercise.^20,21

Over the short term (<1 year), behavioral weight-loss treatment produces similar weight loss in obese patients with or without BED; long-term results in both groups, however, have not been satisfactory.^20,21 No studies have examined the efficacy of specialized diets (such as low-carbohydrate regimens) in patients with BED.

Specialized psychotherapy’s goal is to modify bingeeating behavior with behavioral self-management strategies, reducing interpersonal dysfunction and stress, and/or managing affective dysregulation.

Cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT) have been effective in reducing binge eating, both acutely and for up to 12 months^4,20-24 but less effective in achieving and maintaining weight loss. Patients who achieve remission in binge eating after undergoing CBT or IPI often experience modest but stable weight loss.^20-22 For example, in a comparison study of CBT and IPT:

• After 20 weekly sessions, patients whose binge eating was in remission lost weight (mean body mass index [BMI] −0.5 ± 1.5 kg/m²), whereas those who continued to binge gained weight (mean BMI +0.4 ±2.0 kg/m²).
• At 12 months’ follow-up, patients still in remission continued to lose weight (mean BMI −1.0 ± 3.0 kg/m²), whereas those no longer in remission gained weight (mean BMI +0.7 ±2.9 kg/m²[P = 0.01]).²²

Self-help and dialectical behavioral therapy (DBT) may also help reduce binge eating in BED. As with CBT and IPT, they are less effective in weight loss. In the only controlled study of DBT,²⁴ patients achieved an average 2.5-lb weight loss after 20 weeks of DBT, compared with an average 0.6-lb weight gain in the control group. This difference was not significant, and the report did not include data on weight loss maintenance.

In summary, CBT may be more effective than behavioral weight loss treatment for reducing binge eating, but behavioral weight loss is more effective for weight loss.

Medications for BED

Medications that have been tried for BED include antidepressants, appetite suppressants, and anticonvulsants.^25,26 Antidepressants are used to treat BED because:

• BED is often associated with depressive symptoms and disorders.
• BED is related to bulimia nervosa, and placebo-controlled trials have shown that the binge eating of bulimia nervosa responds to several classes of antidepressants. The selective serotonin reuptake inhibitor (SSRI) fluoxetine is the only medication indicated for treating any eating disorder (bulimia nervosa).
• Bupropion and venlafaxine—a serotonin-norepinephrine reuptake inhibitor (SNRI)—have weight-loss properties.

SSRIs are the most extensively studied antidepressants for treating BED. SSRIs have weightloss properties, but only short term.^25-26 Citalopram, fluoxetine, fluvoxamine, and sertraline have reduced binge eating and body weight more effectively than placebo during 6 to 9 weeks of treatment (Table 2).^25-26 However, one controlled study²³ showed that fluoxetine was not significantly more effective than placebo in reducing binge frequency or body weight after 16 weeks.

TCAs. Studies of tricyclic antidepressants (TCAs) for BED are sparse, and results have been mixed. In one trial, imipramine was similar to placebo in reducing binge frequency and body weight. In a placebo-controlled study of patients with nonpurging bulimia nervosa, desipramine reduced binge eating but had no effect on body weight.^25,26

Table 2

Drug therapies shown to be effective for BED*

Venlafaxine. In a retrospective review of 35 consecutive obese women with BED, venlafaxine, mean 222 mg/d for 28 to 300 days (median 120 days), reduced binge eating, body weight, and depressive symptoms.²⁷

Bupropion has been more effective than placebo for treating:

• uncomplicated obesity (short- and long-term)
• obesity associated with depressive symptoms
• bulimia nervosa (although bupropion is contraindicated in these patients because of seizure risk).^26,28,29

No controlled trials have studied bupropion for BED. When using dosages effective in depressive disorders, we find bupropion helpful in reducing binge eating, body weight, and depressive symptoms in BED patients.

Appetite suppressants decrease appetite and weight, may increase satiety, and may reduce depressive symptoms.

Sibutramine—a serotonin, norepinephrine, and dopamine reuptake inhibitor indicated for managing obesity—has been reported effective in BED in a 12-week, randomized, double-blind, placebo-controlled trial. A 15-mg/d dosage reduced binge frequency, body weight, and depressive symptoms more effectively than placebo in 60 obese patients with BED.³⁰ Most-frequent adverse effects (dry mouth and constipation) were mild and benign, and no significant complications were observed.

Sibutramine’s mechanism of action in BED is unknown. However, it suppressed food intake during binge-eating episodes in patients with BED in a randomized, controlled, cross-over laboratory study.³¹

Orlistat. We know of no published controlled studies of the lipase inhibitor orlistat in treating BED. In our experience, some patients do well with this agent, though we have observed infrequent purging episodes with it in patients with BED.

With orlistat, 120 mg tid, our BED patients have experienced weight loss comparable to that seen in uncomplicated obesity at similar dosages. Orlistat seems most effective for:

• patients whose binge eating is in remission
• those who responded to behavioral weightloss treatment, a psychological treatment, or another medication.

Anticonvulsants such as topiramate and zonisamide have been shown effective in treating obesity^32,33 and are sometimes used to treat BED. Obese BED patients with mood disorders often do best with psychotherapy plus medication

Topiramate at dosages of 50 to 600 mg/d (median 212 mg/d) reduced binge-eating frequency, obsessive-compulsive features of binge eating, and body weight more effectively than placebo in a 14-week study of 61 obese patients with BED. These effects were maintained across 48 weeks in an open-label extension trial.³⁴

Zonisamide, mean 513 mg/d, produced similar results during a prospective, open-label, 12-week trial in 15 patients with BED.³⁵ A controlled trial to replicate these findings is ongoing.

BED may respond to anticonvulsant therapy for several reasons:

• Some anticonvulsants are effective in treating bipolar disorder, which may occur with BED.¹²
• Some anticonvulsants have shown benefit in conditions associated with pathologic impulsivity, such as substance abuse, impulse-control, and cluster B disorders.¹⁰

Growing evidence shows that bulimia nervosa and BED may be associated with pathologic impulsivity.

Combination therapies are generally more effective than monotherapies in patients with mood disorders, uncomplicated obesity, and possibly bulimia nervosa. Even so, few trials have systematically studied combination therapy in managing patients with BED.

Two studies compared psychotherapy and antidepressants alone and in combination in treating BED.^21,23 Both showed that CBT alone was more effective in decreasing binge frequency than desipramine alone,²¹ fluoxetine alone,²³ and the combination of CBT and medication. On the other hand, patients who took desipramine either alone or in combination experienced a greater degree of weight loss than those who did not take desipramine.²¹

In another combination therapy, exercise has been shown to be an effective adjunct to CBT in maintenance treatment of obese women with BED.³⁶

No studies have compared behavioral weight management or a specialized psychotherapy in combination with an antiobesity drug or a weight-loss anticonvulsant in treating BED.

Treatment recommendations

In our experience, BED patients—particularly those with obesity and psychopathology—often do best with some combination of psychological treatment and medication:

• The psychological component may be behavioral weight-loss treatment, a specialized psychotherapy such as CBT or IPT, or some combination of behavioral weight-loss treatment and specialized psychotherapy.
• The medication component may consist of an antidepressant, anticonvulsant, antiobesity drug, or multiple drugs (such as an SSRI or sibutramine with topiramate for BED with major depression, or topiramate with lithium for BED with bipolar disorder).

Although combination therapies may be optimal for some patients, this approach remains unproven in controlled trials.

Patient preference. In addition to comorbidities, patient preference is an important consideration when choosing BED treatments. We determine our patients’ preferences by educating them as much as possible about their options. We explain the benefits and weaknesses of all treatments and encourage them to participate in forming their individualized treatment plans.

Patients sometimes have strong treatment preferences. Some prefer psychological treatments, whereas others prefer medications. Working with patient preferences enhances treatment adherence. For example, patients who fail a preferred treatment are often more willing to adhere to another treatment modality about which they initially were skeptical.

Related resources

• Bray GA, Bouchard C (eds). Handbook of obesity: clinical applications (2nd ed). New York, NY: Marcel Dekker, 2004.
• Cooper Z, Zairburn CG, Hawker DM. Cognitive behavioral treatment of obesity. A clinician’s guide. New York: Guilford Press, 2003.
• Carter WP, Hudson JI, Lalonde JK, et al. Pharmacologic treatment of binge eating disorder. Int J Eat Disord 2003;34(suppl):S74-88.

Drug brand names

• Bupropion • Wellbutrin
• Citalopram • Celexa
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Orlistat • Xenical
• Sertraline • Zoloft
• Sibutramine • Meridia
• Topiramate • Topamax
• Venlafaxine • Effexor
• Zonisamide • Zonegran

Disclosure

Dr. Kotwal receives grant support from Elan Corporation and is a speaker for Ortho-McNeil Pharmaceutical and Pfizer Inc.

Dr. Kaneria and Ms. Guerdjikova report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. McElroy is a consultant to Abbott Laboratories, Bristol-Myers Squibb Co., Elan Corporation, GlaxoSmithKline, Janssen Pharmaceutica, Eli Lilly and Co., and Ortho-McNeil Pharmaceutical. She receives grant/research support from Elan Pharmaceuticals, Forest Pharmaceuticals, Merck & Co., Ortho-McNeil Pharmaceutical, and Sanofi-Synthelabo and is a speaker for Eli Lilly and Co. and Ortho-McNeil Pharmaceutical.

Because no one treatment fits all patients with binge eating disorder, their management usually requires an individualized program of:

• behavioral weight control
• psychotherapy
• and sometimes medications.

In our weight management clinic, we consider medication options based on patient preference and whether BED is uncomplicated (Figure 1) or coexists with a mood disorder (Figure 2).

This article presents the evidence on which we base our comprehensive approach. General psychiatrists with knowledge of BED can treat patients with this eating disorder, although complicated cases may require referral for specialized treatment.

Figure 1 Medication options for uncomplicated BED

Clinical characteristics

Psychiatric comorbidity. BED often occurs in patients with mood, anxiety, substance-abuse, impulsecontrol, and personality disorders.^4,6,10-12 Mood disorder—particularly depression—appears to be the most common comorbidity. BED can occur with bipolar disorder¹²—a comorbidity that in our experience is underrecognized both clinically and in the literature.

Patients with BED and bipolar disorder show increased impulsivity and mood lability. As bipolar II disorder and other “soft-spectrum” forms are more common than bipolar I disorder, BED is also more likely to occur with hypomania than mania.

Overweight. Not surprisingly, BED is associated with overweight and obesity.^5,8,9,11 Not all patients with BED are overweight or obese, but most who participate in clinical trials of BED treatments are at least overweight. BED has been reported in up to:

• 30% of participants in weight-loss programs⁷
• 70% of participants in groups such as Overeaters Anonymous
• 50% of patients who seek bariatric surgery.⁵

In our experience, patients are often more distressed by their weight than by their binge eating, depression, or anxiety. Indeed, overweight and obesity are the usual reasons patients with BED present for treatment at our center.

Diagnosis. BED’s validity as a clinical diagnosis has been controversial since the disorder was first included in DSM-IV (Table 1).³ Debate continues about some definitions in the DSM criteria, including what amount of food is “definitely larger” than most people would eat and what is “loss of control over eating.”

Nevertheless, screening for BED is relatively easy. Clinicians may use the eating disorder section of the Structured Clinical Interview for DSM-IV or the Eating Disorders Examination. Alternatively, simply ask patients if they have episodes of uncontrollable overeating, during which they eat unusually large amounts of food and their eating feels out of control.

Course. BED begins in adolescence or adulthood. Disease course is variable, with periods of remission, recurrence, and chronicity.^6,7,10 Interestingly, one prospective study showed that even if the binge eating resolves, persons may still develop obesity.¹³

Prevalence. BED affects 1.5% to 3% of the U.S. population. It is more common in women than men, equally prevalent in whites and blacks, and more prevalent than anorexia nervosa and bulimia nervosa combined.^11,14 Subthreshold BED—such as obesity with infrequent or nondistressing binge eating—appears to be much more common,¹⁰ although no data are available.

Theories of binge eating

BED’s cause is unknown, but biological, familial, and psychosocial factors have been implicated.

Biological factors. The neurotransmitters serotonin (5-HT) and dopamine—as well as various peptides—have been shown to help regulate feeding behavior.¹⁰

Table 1

Diagnostic criteria for binge-eating disorder*

Serotonin. Reduced 5-HT transporter binding has been shown in obese women with BED.¹⁵ Their 5-HT binding improved and binge eating subsided with group psychotherapy and fluoxetine, although the women continued to gain weight.

Figure 2 Medication options for BED with obesity and a mood disorder*

Genetic factors. In severely obese patients (body mass index 44±2), those with a DSM-IV diagnosis of BED exhibited mutations of the melanocortin 4 receptor gene, which affects the anorectic properties of alpha melanocyte-stimulating hormone.¹⁷

Familial factors associated with BED include parental depression and obesity.¹⁸

Psychosocial correlates include physical and sexual abuse, bullying by peers, and discrimination because of being overweight.¹⁹

Treatment recommendations

Few systematic studies have examined BED treatment. Emerging research suggests that behavioral weight-loss treatment, specialized psychotherapies, and medications may be effective in some patients with BED.^4,6,8

Behavioral weight-loss treatment’s main goal is to manage the patient’s weight with a lower-calorie, healthy diet and to increase exercise.^20,21

Over the short term (<1 year), behavioral weight-loss treatment produces similar weight loss in obese patients with or without BED; long-term results in both groups, however, have not been satisfactory.^20,21 No studies have examined the efficacy of specialized diets (such as low-carbohydrate regimens) in patients with BED.

Specialized psychotherapy’s goal is to modify bingeeating behavior with behavioral self-management strategies, reducing interpersonal dysfunction and stress, and/or managing affective dysregulation.

Cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT) have been effective in reducing binge eating, both acutely and for up to 12 months^4,20-24 but less effective in achieving and maintaining weight loss. Patients who achieve remission in binge eating after undergoing CBT or IPI often experience modest but stable weight loss.^20-22 For example, in a comparison study of CBT and IPT:

• After 20 weekly sessions, patients whose binge eating was in remission lost weight (mean body mass index [BMI] −0.5 ± 1.5 kg/m²), whereas those who continued to binge gained weight (mean BMI +0.4 ±2.0 kg/m²).
• At 12 months’ follow-up, patients still in remission continued to lose weight (mean BMI −1.0 ± 3.0 kg/m²), whereas those no longer in remission gained weight (mean BMI +0.7 ±2.9 kg/m²[P = 0.01]).²²

Self-help and dialectical behavioral therapy (DBT) may also help reduce binge eating in BED. As with CBT and IPT, they are less effective in weight loss. In the only controlled study of DBT,²⁴ patients achieved an average 2.5-lb weight loss after 20 weeks of DBT, compared with an average 0.6-lb weight gain in the control group. This difference was not significant, and the report did not include data on weight loss maintenance.

In summary, CBT may be more effective than behavioral weight loss treatment for reducing binge eating, but behavioral weight loss is more effective for weight loss.

Medications for BED

Medications that have been tried for BED include antidepressants, appetite suppressants, and anticonvulsants.^25,26 Antidepressants are used to treat BED because:

• BED is often associated with depressive symptoms and disorders.
• BED is related to bulimia nervosa, and placebo-controlled trials have shown that the binge eating of bulimia nervosa responds to several classes of antidepressants. The selective serotonin reuptake inhibitor (SSRI) fluoxetine is the only medication indicated for treating any eating disorder (bulimia nervosa).
• Bupropion and venlafaxine—a serotonin-norepinephrine reuptake inhibitor (SNRI)—have weight-loss properties.

SSRIs are the most extensively studied antidepressants for treating BED. SSRIs have weightloss properties, but only short term.^25-26 Citalopram, fluoxetine, fluvoxamine, and sertraline have reduced binge eating and body weight more effectively than placebo during 6 to 9 weeks of treatment (Table 2).^25-26 However, one controlled study²³ showed that fluoxetine was not significantly more effective than placebo in reducing binge frequency or body weight after 16 weeks.

TCAs. Studies of tricyclic antidepressants (TCAs) for BED are sparse, and results have been mixed. In one trial, imipramine was similar to placebo in reducing binge frequency and body weight. In a placebo-controlled study of patients with nonpurging bulimia nervosa, desipramine reduced binge eating but had no effect on body weight.^25,26

Table 2

Drug therapies shown to be effective for BED*

Venlafaxine. In a retrospective review of 35 consecutive obese women with BED, venlafaxine, mean 222 mg/d for 28 to 300 days (median 120 days), reduced binge eating, body weight, and depressive symptoms.²⁷

Bupropion has been more effective than placebo for treating:

• uncomplicated obesity (short- and long-term)
• obesity associated with depressive symptoms
• bulimia nervosa (although bupropion is contraindicated in these patients because of seizure risk).^26,28,29

No controlled trials have studied bupropion for BED. When using dosages effective in depressive disorders, we find bupropion helpful in reducing binge eating, body weight, and depressive symptoms in BED patients.

Appetite suppressants decrease appetite and weight, may increase satiety, and may reduce depressive symptoms.

Sibutramine—a serotonin, norepinephrine, and dopamine reuptake inhibitor indicated for managing obesity—has been reported effective in BED in a 12-week, randomized, double-blind, placebo-controlled trial. A 15-mg/d dosage reduced binge frequency, body weight, and depressive symptoms more effectively than placebo in 60 obese patients with BED.³⁰ Most-frequent adverse effects (dry mouth and constipation) were mild and benign, and no significant complications were observed.

Sibutramine’s mechanism of action in BED is unknown. However, it suppressed food intake during binge-eating episodes in patients with BED in a randomized, controlled, cross-over laboratory study.³¹

Orlistat. We know of no published controlled studies of the lipase inhibitor orlistat in treating BED. In our experience, some patients do well with this agent, though we have observed infrequent purging episodes with it in patients with BED.

With orlistat, 120 mg tid, our BED patients have experienced weight loss comparable to that seen in uncomplicated obesity at similar dosages. Orlistat seems most effective for:

• patients whose binge eating is in remission
• those who responded to behavioral weightloss treatment, a psychological treatment, or another medication.

Anticonvulsants such as topiramate and zonisamide have been shown effective in treating obesity^32,33 and are sometimes used to treat BED. Obese BED patients with mood disorders often do best with psychotherapy plus medication

Topiramate at dosages of 50 to 600 mg/d (median 212 mg/d) reduced binge-eating frequency, obsessive-compulsive features of binge eating, and body weight more effectively than placebo in a 14-week study of 61 obese patients with BED. These effects were maintained across 48 weeks in an open-label extension trial.³⁴

Zonisamide, mean 513 mg/d, produced similar results during a prospective, open-label, 12-week trial in 15 patients with BED.³⁵ A controlled trial to replicate these findings is ongoing.

BED may respond to anticonvulsant therapy for several reasons:

• Some anticonvulsants are effective in treating bipolar disorder, which may occur with BED.¹²
• Some anticonvulsants have shown benefit in conditions associated with pathologic impulsivity, such as substance abuse, impulse-control, and cluster B disorders.¹⁰

Growing evidence shows that bulimia nervosa and BED may be associated with pathologic impulsivity.

Combination therapies are generally more effective than monotherapies in patients with mood disorders, uncomplicated obesity, and possibly bulimia nervosa. Even so, few trials have systematically studied combination therapy in managing patients with BED.

Two studies compared psychotherapy and antidepressants alone and in combination in treating BED.^21,23 Both showed that CBT alone was more effective in decreasing binge frequency than desipramine alone,²¹ fluoxetine alone,²³ and the combination of CBT and medication. On the other hand, patients who took desipramine either alone or in combination experienced a greater degree of weight loss than those who did not take desipramine.²¹

In another combination therapy, exercise has been shown to be an effective adjunct to CBT in maintenance treatment of obese women with BED.³⁶

No studies have compared behavioral weight management or a specialized psychotherapy in combination with an antiobesity drug or a weight-loss anticonvulsant in treating BED.

Treatment recommendations

In our experience, BED patients—particularly those with obesity and psychopathology—often do best with some combination of psychological treatment and medication:

• The psychological component may be behavioral weight-loss treatment, a specialized psychotherapy such as CBT or IPT, or some combination of behavioral weight-loss treatment and specialized psychotherapy.
• The medication component may consist of an antidepressant, anticonvulsant, antiobesity drug, or multiple drugs (such as an SSRI or sibutramine with topiramate for BED with major depression, or topiramate with lithium for BED with bipolar disorder).

Although combination therapies may be optimal for some patients, this approach remains unproven in controlled trials.

Patient preference. In addition to comorbidities, patient preference is an important consideration when choosing BED treatments. We determine our patients’ preferences by educating them as much as possible about their options. We explain the benefits and weaknesses of all treatments and encourage them to participate in forming their individualized treatment plans.

Patients sometimes have strong treatment preferences. Some prefer psychological treatments, whereas others prefer medications. Working with patient preferences enhances treatment adherence. For example, patients who fail a preferred treatment are often more willing to adhere to another treatment modality about which they initially were skeptical.

Related resources

• Bray GA, Bouchard C (eds). Handbook of obesity: clinical applications (2nd ed). New York, NY: Marcel Dekker, 2004.
• Cooper Z, Zairburn CG, Hawker DM. Cognitive behavioral treatment of obesity. A clinician’s guide. New York: Guilford Press, 2003.
• Carter WP, Hudson JI, Lalonde JK, et al. Pharmacologic treatment of binge eating disorder. Int J Eat Disord 2003;34(suppl):S74-88.

Drug brand names

• Bupropion • Wellbutrin
• Citalopram • Celexa
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Orlistat • Xenical
• Sertraline • Zoloft
• Sibutramine • Meridia
• Topiramate • Topamax
• Venlafaxine • Effexor
• Zonisamide • Zonegran

Disclosure

Dr. Kotwal receives grant support from Elan Corporation and is a speaker for Ortho-McNeil Pharmaceutical and Pfizer Inc.

Dr. Kaneria and Ms. Guerdjikova report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. McElroy is a consultant to Abbott Laboratories, Bristol-Myers Squibb Co., Elan Corporation, GlaxoSmithKline, Janssen Pharmaceutica, Eli Lilly and Co., and Ortho-McNeil Pharmaceutical. She receives grant/research support from Elan Pharmaceuticals, Forest Pharmaceuticals, Merck & Co., Ortho-McNeil Pharmaceutical, and Sanofi-Synthelabo and is a speaker for Eli Lilly and Co. and Ortho-McNeil Pharmaceutical.

Because no one treatment fits all patients with binge eating disorder, their management usually requires an individualized program of:

• behavioral weight control
• psychotherapy
• and sometimes medications.

In our weight management clinic, we consider medication options based on patient preference and whether BED is uncomplicated (Figure 1) or coexists with a mood disorder (Figure 2).

This article presents the evidence on which we base our comprehensive approach. General psychiatrists with knowledge of BED can treat patients with this eating disorder, although complicated cases may require referral for specialized treatment.

Figure 1 Medication options for uncomplicated BED

Clinical characteristics

Psychiatric comorbidity. BED often occurs in patients with mood, anxiety, substance-abuse, impulsecontrol, and personality disorders.^4,6,10-12 Mood disorder—particularly depression—appears to be the most common comorbidity. BED can occur with bipolar disorder¹²—a comorbidity that in our experience is underrecognized both clinically and in the literature.

Patients with BED and bipolar disorder show increased impulsivity and mood lability. As bipolar II disorder and other “soft-spectrum” forms are more common than bipolar I disorder, BED is also more likely to occur with hypomania than mania.

Overweight. Not surprisingly, BED is associated with overweight and obesity.^5,8,9,11 Not all patients with BED are overweight or obese, but most who participate in clinical trials of BED treatments are at least overweight. BED has been reported in up to:

• 30% of participants in weight-loss programs⁷
• 70% of participants in groups such as Overeaters Anonymous
• 50% of patients who seek bariatric surgery.⁵

In our experience, patients are often more distressed by their weight than by their binge eating, depression, or anxiety. Indeed, overweight and obesity are the usual reasons patients with BED present for treatment at our center.

Diagnosis. BED’s validity as a clinical diagnosis has been controversial since the disorder was first included in DSM-IV (Table 1).³ Debate continues about some definitions in the DSM criteria, including what amount of food is “definitely larger” than most people would eat and what is “loss of control over eating.”

Nevertheless, screening for BED is relatively easy. Clinicians may use the eating disorder section of the Structured Clinical Interview for DSM-IV or the Eating Disorders Examination. Alternatively, simply ask patients if they have episodes of uncontrollable overeating, during which they eat unusually large amounts of food and their eating feels out of control.

Course. BED begins in adolescence or adulthood. Disease course is variable, with periods of remission, recurrence, and chronicity.^6,7,10 Interestingly, one prospective study showed that even if the binge eating resolves, persons may still develop obesity.¹³

Prevalence. BED affects 1.5% to 3% of the U.S. population. It is more common in women than men, equally prevalent in whites and blacks, and more prevalent than anorexia nervosa and bulimia nervosa combined.^11,14 Subthreshold BED—such as obesity with infrequent or nondistressing binge eating—appears to be much more common,¹⁰ although no data are available.

Theories of binge eating

BED’s cause is unknown, but biological, familial, and psychosocial factors have been implicated.

Biological factors. The neurotransmitters serotonin (5-HT) and dopamine—as well as various peptides—have been shown to help regulate feeding behavior.¹⁰

Table 1

Diagnostic criteria for binge-eating disorder*

Serotonin. Reduced 5-HT transporter binding has been shown in obese women with BED.¹⁵ Their 5-HT binding improved and binge eating subsided with group psychotherapy and fluoxetine, although the women continued to gain weight.

Figure 2 Medication options for BED with obesity and a mood disorder*

Genetic factors. In severely obese patients (body mass index 44±2), those with a DSM-IV diagnosis of BED exhibited mutations of the melanocortin 4 receptor gene, which affects the anorectic properties of alpha melanocyte-stimulating hormone.¹⁷

Familial factors associated with BED include parental depression and obesity.¹⁸

Psychosocial correlates include physical and sexual abuse, bullying by peers, and discrimination because of being overweight.¹⁹

Treatment recommendations

Few systematic studies have examined BED treatment. Emerging research suggests that behavioral weight-loss treatment, specialized psychotherapies, and medications may be effective in some patients with BED.^4,6,8

Behavioral weight-loss treatment’s main goal is to manage the patient’s weight with a lower-calorie, healthy diet and to increase exercise.^20,21

Over the short term (<1 year), behavioral weight-loss treatment produces similar weight loss in obese patients with or without BED; long-term results in both groups, however, have not been satisfactory.^20,21 No studies have examined the efficacy of specialized diets (such as low-carbohydrate regimens) in patients with BED.

Specialized psychotherapy’s goal is to modify bingeeating behavior with behavioral self-management strategies, reducing interpersonal dysfunction and stress, and/or managing affective dysregulation.

Cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT) have been effective in reducing binge eating, both acutely and for up to 12 months^4,20-24 but less effective in achieving and maintaining weight loss. Patients who achieve remission in binge eating after undergoing CBT or IPI often experience modest but stable weight loss.^20-22 For example, in a comparison study of CBT and IPT:

• After 20 weekly sessions, patients whose binge eating was in remission lost weight (mean body mass index [BMI] −0.5 ± 1.5 kg/m²), whereas those who continued to binge gained weight (mean BMI +0.4 ±2.0 kg/m²).
• At 12 months’ follow-up, patients still in remission continued to lose weight (mean BMI −1.0 ± 3.0 kg/m²), whereas those no longer in remission gained weight (mean BMI +0.7 ±2.9 kg/m²[P = 0.01]).²²

Self-help and dialectical behavioral therapy (DBT) may also help reduce binge eating in BED. As with CBT and IPT, they are less effective in weight loss. In the only controlled study of DBT,²⁴ patients achieved an average 2.5-lb weight loss after 20 weeks of DBT, compared with an average 0.6-lb weight gain in the control group. This difference was not significant, and the report did not include data on weight loss maintenance.

In summary, CBT may be more effective than behavioral weight loss treatment for reducing binge eating, but behavioral weight loss is more effective for weight loss.

Medications for BED

Medications that have been tried for BED include antidepressants, appetite suppressants, and anticonvulsants.^25,26 Antidepressants are used to treat BED because:

• BED is often associated with depressive symptoms and disorders.
• BED is related to bulimia nervosa, and placebo-controlled trials have shown that the binge eating of bulimia nervosa responds to several classes of antidepressants. The selective serotonin reuptake inhibitor (SSRI) fluoxetine is the only medication indicated for treating any eating disorder (bulimia nervosa).
• Bupropion and venlafaxine—a serotonin-norepinephrine reuptake inhibitor (SNRI)—have weight-loss properties.

SSRIs are the most extensively studied antidepressants for treating BED. SSRIs have weightloss properties, but only short term.^25-26 Citalopram, fluoxetine, fluvoxamine, and sertraline have reduced binge eating and body weight more effectively than placebo during 6 to 9 weeks of treatment (Table 2).^25-26 However, one controlled study²³ showed that fluoxetine was not significantly more effective than placebo in reducing binge frequency or body weight after 16 weeks.

TCAs. Studies of tricyclic antidepressants (TCAs) for BED are sparse, and results have been mixed. In one trial, imipramine was similar to placebo in reducing binge frequency and body weight. In a placebo-controlled study of patients with nonpurging bulimia nervosa, desipramine reduced binge eating but had no effect on body weight.^25,26

Table 2

Drug therapies shown to be effective for BED*

Venlafaxine. In a retrospective review of 35 consecutive obese women with BED, venlafaxine, mean 222 mg/d for 28 to 300 days (median 120 days), reduced binge eating, body weight, and depressive symptoms.²⁷

Bupropion has been more effective than placebo for treating:

• uncomplicated obesity (short- and long-term)
• obesity associated with depressive symptoms
• bulimia nervosa (although bupropion is contraindicated in these patients because of seizure risk).^26,28,29

No controlled trials have studied bupropion for BED. When using dosages effective in depressive disorders, we find bupropion helpful in reducing binge eating, body weight, and depressive symptoms in BED patients.

Appetite suppressants decrease appetite and weight, may increase satiety, and may reduce depressive symptoms.

Sibutramine—a serotonin, norepinephrine, and dopamine reuptake inhibitor indicated for managing obesity—has been reported effective in BED in a 12-week, randomized, double-blind, placebo-controlled trial. A 15-mg/d dosage reduced binge frequency, body weight, and depressive symptoms more effectively than placebo in 60 obese patients with BED.³⁰ Most-frequent adverse effects (dry mouth and constipation) were mild and benign, and no significant complications were observed.

Sibutramine’s mechanism of action in BED is unknown. However, it suppressed food intake during binge-eating episodes in patients with BED in a randomized, controlled, cross-over laboratory study.³¹

Orlistat. We know of no published controlled studies of the lipase inhibitor orlistat in treating BED. In our experience, some patients do well with this agent, though we have observed infrequent purging episodes with it in patients with BED.

With orlistat, 120 mg tid, our BED patients have experienced weight loss comparable to that seen in uncomplicated obesity at similar dosages. Orlistat seems most effective for:

• patients whose binge eating is in remission
• those who responded to behavioral weightloss treatment, a psychological treatment, or another medication.

Anticonvulsants such as topiramate and zonisamide have been shown effective in treating obesity^32,33 and are sometimes used to treat BED. Obese BED patients with mood disorders often do best with psychotherapy plus medication

Topiramate at dosages of 50 to 600 mg/d (median 212 mg/d) reduced binge-eating frequency, obsessive-compulsive features of binge eating, and body weight more effectively than placebo in a 14-week study of 61 obese patients with BED. These effects were maintained across 48 weeks in an open-label extension trial.³⁴

Zonisamide, mean 513 mg/d, produced similar results during a prospective, open-label, 12-week trial in 15 patients with BED.³⁵ A controlled trial to replicate these findings is ongoing.

BED may respond to anticonvulsant therapy for several reasons:

• Some anticonvulsants are effective in treating bipolar disorder, which may occur with BED.¹²
• Some anticonvulsants have shown benefit in conditions associated with pathologic impulsivity, such as substance abuse, impulse-control, and cluster B disorders.¹⁰

Growing evidence shows that bulimia nervosa and BED may be associated with pathologic impulsivity.

Combination therapies are generally more effective than monotherapies in patients with mood disorders, uncomplicated obesity, and possibly bulimia nervosa. Even so, few trials have systematically studied combination therapy in managing patients with BED.

Two studies compared psychotherapy and antidepressants alone and in combination in treating BED.^21,23 Both showed that CBT alone was more effective in decreasing binge frequency than desipramine alone,²¹ fluoxetine alone,²³ and the combination of CBT and medication. On the other hand, patients who took desipramine either alone or in combination experienced a greater degree of weight loss than those who did not take desipramine.²¹

In another combination therapy, exercise has been shown to be an effective adjunct to CBT in maintenance treatment of obese women with BED.³⁶

No studies have compared behavioral weight management or a specialized psychotherapy in combination with an antiobesity drug or a weight-loss anticonvulsant in treating BED.

Treatment recommendations

In our experience, BED patients—particularly those with obesity and psychopathology—often do best with some combination of psychological treatment and medication:

• The psychological component may be behavioral weight-loss treatment, a specialized psychotherapy such as CBT or IPT, or some combination of behavioral weight-loss treatment and specialized psychotherapy.
• The medication component may consist of an antidepressant, anticonvulsant, antiobesity drug, or multiple drugs (such as an SSRI or sibutramine with topiramate for BED with major depression, or topiramate with lithium for BED with bipolar disorder).

Although combination therapies may be optimal for some patients, this approach remains unproven in controlled trials.

Patient preference. In addition to comorbidities, patient preference is an important consideration when choosing BED treatments. We determine our patients’ preferences by educating them as much as possible about their options. We explain the benefits and weaknesses of all treatments and encourage them to participate in forming their individualized treatment plans.

Patients sometimes have strong treatment preferences. Some prefer psychological treatments, whereas others prefer medications. Working with patient preferences enhances treatment adherence. For example, patients who fail a preferred treatment are often more willing to adhere to another treatment modality about which they initially were skeptical.

Related resources

• Bray GA, Bouchard C (eds). Handbook of obesity: clinical applications (2nd ed). New York, NY: Marcel Dekker, 2004.
• Cooper Z, Zairburn CG, Hawker DM. Cognitive behavioral treatment of obesity. A clinician’s guide. New York: Guilford Press, 2003.
• Carter WP, Hudson JI, Lalonde JK, et al. Pharmacologic treatment of binge eating disorder. Int J Eat Disord 2003;34(suppl):S74-88.

Drug brand names

• Bupropion • Wellbutrin
• Citalopram • Celexa
• Desipramine • Norpramin
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Orlistat • Xenical
• Sertraline • Zoloft
• Sibutramine • Meridia
• Topiramate • Topamax
• Venlafaxine • Effexor
• Zonisamide • Zonegran

Disclosure

Dr. Kotwal receives grant support from Elan Corporation and is a speaker for Ortho-McNeil Pharmaceutical and Pfizer Inc.

Dr. Kaneria and Ms. Guerdjikova report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. McElroy is a consultant to Abbott Laboratories, Bristol-Myers Squibb Co., Elan Corporation, GlaxoSmithKline, Janssen Pharmaceutica, Eli Lilly and Co., and Ortho-McNeil Pharmaceutical. She receives grant/research support from Elan Pharmaceuticals, Forest Pharmaceuticals, Merck & Co., Ortho-McNeil Pharmaceutical, and Sanofi-Synthelabo and is a speaker for Eli Lilly and Co. and Ortho-McNeil Pharmaceutical.

Evidence summary

Asthma is characterized by inflammation of the bronchial airways. Leukotrienes are potent mediators of inflammation and are believed to contribute significantly to the inflammatory pathophysiology of asthma. Leukotriene inhibitors interfere with leukotriene production or leukotriene receptors and thus inhibit inflammation.¹

Leukotriene inhibitors are administered orally, a significant advantage over inhalation in the pediatric population. For children, the theoretical corticosteroid-sparing effect of leukotriene inhibitors is appealing but has not been demonstrated.

In January 2002, Cochrane reviewers identified 3 studies of leukotriene inhibitor use in children that met their quality criteria for meta-analysis. Unfortunately, recent changes in asthma classification terminology make it difficult to precisely translate past studies into current practice. Based on these studies, the Cochrane reviewers concluded there is insufficient evidence to support the use of leukotriene inhibitors in children as monotherapy or as an addition to corticosteroids.^1,2

One randomized, double-blind crossover study of 279 children with corticosteroid-dependent (persistent) asthma compared montelukast 5 mg (Singulair) once a day plus inhaled budesonide 200 μg (Pulmicort) twice a day with placebo plus budesonide (Rhinocort). Each study period lasted only 4 weeks, starting after a 4-week run-in period. Montelukast modestly improved asthma control over placebo. Compared with the placebo period, montelukast decreased the average use of beta-agonists by 1 puff per day. Asthma exacerbation days decreased by about 1 per month during montelukast treatment. The effects of montelukast and placebo on forced expiratory volume in 1 second (FEV₁), quality of life, and adverse events did not differ significantly.³

One randomized, open-label crossover study of 124 children with “mild” asthma found that montelukast provided equivalent control and superior patient and parent satisfaction when compared with inhaled corticosteroids. Outcomes assessed were FEV₁, school and work loss, medical resource utilization, safety, and patient and parent satisfaction. Children entering this study were self-selected to extend participation from a previous larger study that did not meet Cochrane quality criteria for inclusion in meta-analysis. The authors acknowledge the potential for selection bias.⁴

A randomized, double-blind, placebo-controlled study of 338 patients aged 12 years to adult compared zafirlukast (Accolate) with fluticasone propionate (Flovent) for control of persistent asthma. This study concluded that fluticasone was superior for all clinical outcomes measured including symptom scores, albuterol use, nighttime awakenings pulmonary function, and number of exacerbations requiring oral corticosteroids. Pooling of adult and adolescent cases in this study limits generalized application of these results to pediatric practice.⁵

Recommendations from others

The National Asthma Education and Prevention Program⁶ and the Global Initiative for Asthma⁷ guidelines conclude that inhaled corticosteroid, at the lowest effective dose, is the preferred therapy for children of all ages with persistent asthma whether mild, moderate, or severe.

Both guidelines list leukotriene inhibitors as a potential adjunct to corticosteroids for moderate persistent asthma, as an alternative to corticosteroids plus long-acting beta₂-agonist. The guidelines also list leukotriene inhibitors as an alternative treatment to inhaled corticosteroids for mild persistent asthma in patients aged >5 years. Montelukast (Singulair) is approved for use in children aged ≥12 months, zafirlukast (Accolate) is approved for children aged≥5 years, and zileuton (Zyflo) is approved only for children aged >12 years.

Evidence summary

Asthma is characterized by inflammation of the bronchial airways. Leukotrienes are potent mediators of inflammation and are believed to contribute significantly to the inflammatory pathophysiology of asthma. Leukotriene inhibitors interfere with leukotriene production or leukotriene receptors and thus inhibit inflammation.¹

Leukotriene inhibitors are administered orally, a significant advantage over inhalation in the pediatric population. For children, the theoretical corticosteroid-sparing effect of leukotriene inhibitors is appealing but has not been demonstrated.

In January 2002, Cochrane reviewers identified 3 studies of leukotriene inhibitor use in children that met their quality criteria for meta-analysis. Unfortunately, recent changes in asthma classification terminology make it difficult to precisely translate past studies into current practice. Based on these studies, the Cochrane reviewers concluded there is insufficient evidence to support the use of leukotriene inhibitors in children as monotherapy or as an addition to corticosteroids.^1,2

One randomized, double-blind crossover study of 279 children with corticosteroid-dependent (persistent) asthma compared montelukast 5 mg (Singulair) once a day plus inhaled budesonide 200 μg (Pulmicort) twice a day with placebo plus budesonide (Rhinocort). Each study period lasted only 4 weeks, starting after a 4-week run-in period. Montelukast modestly improved asthma control over placebo. Compared with the placebo period, montelukast decreased the average use of beta-agonists by 1 puff per day. Asthma exacerbation days decreased by about 1 per month during montelukast treatment. The effects of montelukast and placebo on forced expiratory volume in 1 second (FEV₁), quality of life, and adverse events did not differ significantly.³

One randomized, open-label crossover study of 124 children with “mild” asthma found that montelukast provided equivalent control and superior patient and parent satisfaction when compared with inhaled corticosteroids. Outcomes assessed were FEV₁, school and work loss, medical resource utilization, safety, and patient and parent satisfaction. Children entering this study were self-selected to extend participation from a previous larger study that did not meet Cochrane quality criteria for inclusion in meta-analysis. The authors acknowledge the potential for selection bias.⁴

A randomized, double-blind, placebo-controlled study of 338 patients aged 12 years to adult compared zafirlukast (Accolate) with fluticasone propionate (Flovent) for control of persistent asthma. This study concluded that fluticasone was superior for all clinical outcomes measured including symptom scores, albuterol use, nighttime awakenings pulmonary function, and number of exacerbations requiring oral corticosteroids. Pooling of adult and adolescent cases in this study limits generalized application of these results to pediatric practice.⁵

Recommendations from others

The National Asthma Education and Prevention Program⁶ and the Global Initiative for Asthma⁷ guidelines conclude that inhaled corticosteroid, at the lowest effective dose, is the preferred therapy for children of all ages with persistent asthma whether mild, moderate, or severe.

Both guidelines list leukotriene inhibitors as a potential adjunct to corticosteroids for moderate persistent asthma, as an alternative to corticosteroids plus long-acting beta₂-agonist. The guidelines also list leukotriene inhibitors as an alternative treatment to inhaled corticosteroids for mild persistent asthma in patients aged >5 years. Montelukast (Singulair) is approved for use in children aged ≥12 months, zafirlukast (Accolate) is approved for children aged≥5 years, and zileuton (Zyflo) is approved only for children aged >12 years.

Evidence summary

Asthma is characterized by inflammation of the bronchial airways. Leukotrienes are potent mediators of inflammation and are believed to contribute significantly to the inflammatory pathophysiology of asthma. Leukotriene inhibitors interfere with leukotriene production or leukotriene receptors and thus inhibit inflammation.¹

Leukotriene inhibitors are administered orally, a significant advantage over inhalation in the pediatric population. For children, the theoretical corticosteroid-sparing effect of leukotriene inhibitors is appealing but has not been demonstrated.

In January 2002, Cochrane reviewers identified 3 studies of leukotriene inhibitor use in children that met their quality criteria for meta-analysis. Unfortunately, recent changes in asthma classification terminology make it difficult to precisely translate past studies into current practice. Based on these studies, the Cochrane reviewers concluded there is insufficient evidence to support the use of leukotriene inhibitors in children as monotherapy or as an addition to corticosteroids.^1,2

One randomized, double-blind crossover study of 279 children with corticosteroid-dependent (persistent) asthma compared montelukast 5 mg (Singulair) once a day plus inhaled budesonide 200 μg (Pulmicort) twice a day with placebo plus budesonide (Rhinocort). Each study period lasted only 4 weeks, starting after a 4-week run-in period. Montelukast modestly improved asthma control over placebo. Compared with the placebo period, montelukast decreased the average use of beta-agonists by 1 puff per day. Asthma exacerbation days decreased by about 1 per month during montelukast treatment. The effects of montelukast and placebo on forced expiratory volume in 1 second (FEV₁), quality of life, and adverse events did not differ significantly.³

One randomized, open-label crossover study of 124 children with “mild” asthma found that montelukast provided equivalent control and superior patient and parent satisfaction when compared with inhaled corticosteroids. Outcomes assessed were FEV₁, school and work loss, medical resource utilization, safety, and patient and parent satisfaction. Children entering this study were self-selected to extend participation from a previous larger study that did not meet Cochrane quality criteria for inclusion in meta-analysis. The authors acknowledge the potential for selection bias.⁴

A randomized, double-blind, placebo-controlled study of 338 patients aged 12 years to adult compared zafirlukast (Accolate) with fluticasone propionate (Flovent) for control of persistent asthma. This study concluded that fluticasone was superior for all clinical outcomes measured including symptom scores, albuterol use, nighttime awakenings pulmonary function, and number of exacerbations requiring oral corticosteroids. Pooling of adult and adolescent cases in this study limits generalized application of these results to pediatric practice.⁵

Recommendations from others

The National Asthma Education and Prevention Program⁶ and the Global Initiative for Asthma⁷ guidelines conclude that inhaled corticosteroid, at the lowest effective dose, is the preferred therapy for children of all ages with persistent asthma whether mild, moderate, or severe.

Both guidelines list leukotriene inhibitors as a potential adjunct to corticosteroids for moderate persistent asthma, as an alternative to corticosteroids plus long-acting beta₂-agonist. The guidelines also list leukotriene inhibitors as an alternative treatment to inhaled corticosteroids for mild persistent asthma in patients aged >5 years. Montelukast (Singulair) is approved for use in children aged ≥12 months, zafirlukast (Accolate) is approved for children aged≥5 years, and zileuton (Zyflo) is approved only for children aged >12 years.

Shift work sleep disorder is common among persons whose working hours fall between 6 PM and 7 AM. Some night or overnight shift workers cannot stay alert at work or sleep well when off duty, endangering others on the job or while driving.

When shift work sleep disorder is suspected, find out:

• Is the patient getting enough sleep? The average rotating shift worker sleeps 6 hours nightly¹ while working the night shift.
• Is another sleep disorder present? Obstructive sleep apnea, restless legs syndrome, or other common comorbidities may also be disrupting sleep.
• Is an unrecognized comorbid psychiatric disorder present? Not surprisingly, major depression, chemical dependency, and other untreated psychiatric disorders impede adherence to a sleep schedule.
• Is caffeine being used appropriately? Shift workers can effectively use caffeine as an alerting agent but should only use it within 4 to 6 hours after arising. Advise patients against consuming beverages or foods containing caffeine within 8 to 10 hours of bedtime.

Promoting sleep

To help the patient get ample sleep, encourage him or her to:

• find time for uninterrupted sleep. Family time, social events, and errands must be scheduled so that they do not interfere.
• maintain a consistent sleep schedule when possible. Workers with long night shifts should try to stay awake all night and sleep during the day, even on days off.
• use bright lights during waking hours to promote alertness and prevent sleep disruption. Bright light has been shown to influence the human circadian clock.²

Some workplaces are installing artificial lights to increase light exposure during night work. Night shift workers traveling home in the morning should wear sunglasses to limit light exposure.

Also consider prescribing:

• a short-acting hypnotic. Although not specifically FDA-approved for shift work sleep disorder, medications such as zaleplon or zolpidem can reduce time to falling asleep and increase sleep without producing a hangover effect.
• a wakefulness-promoting agent. The FDA recently approved modafinil for reducing excessive daytime sleepiness in shift work sleep disorder. Patients take modafinil, 200 mg/d, shortly after arising to increase alertness at work. Be sure to advise patients that the medication is not a substitute for getting adequate sleep.

Shift work sleep disorder is common among persons whose working hours fall between 6 PM and 7 AM. Some night or overnight shift workers cannot stay alert at work or sleep well when off duty, endangering others on the job or while driving.

When shift work sleep disorder is suspected, find out:

• Is the patient getting enough sleep? The average rotating shift worker sleeps 6 hours nightly¹ while working the night shift.
• Is another sleep disorder present? Obstructive sleep apnea, restless legs syndrome, or other common comorbidities may also be disrupting sleep.
• Is an unrecognized comorbid psychiatric disorder present? Not surprisingly, major depression, chemical dependency, and other untreated psychiatric disorders impede adherence to a sleep schedule.
• Is caffeine being used appropriately? Shift workers can effectively use caffeine as an alerting agent but should only use it within 4 to 6 hours after arising. Advise patients against consuming beverages or foods containing caffeine within 8 to 10 hours of bedtime.

Promoting sleep

To help the patient get ample sleep, encourage him or her to:

• find time for uninterrupted sleep. Family time, social events, and errands must be scheduled so that they do not interfere.
• maintain a consistent sleep schedule when possible. Workers with long night shifts should try to stay awake all night and sleep during the day, even on days off.
• use bright lights during waking hours to promote alertness and prevent sleep disruption. Bright light has been shown to influence the human circadian clock.²

Some workplaces are installing artificial lights to increase light exposure during night work. Night shift workers traveling home in the morning should wear sunglasses to limit light exposure.

Also consider prescribing:

• a short-acting hypnotic. Although not specifically FDA-approved for shift work sleep disorder, medications such as zaleplon or zolpidem can reduce time to falling asleep and increase sleep without producing a hangover effect.
• a wakefulness-promoting agent. The FDA recently approved modafinil for reducing excessive daytime sleepiness in shift work sleep disorder. Patients take modafinil, 200 mg/d, shortly after arising to increase alertness at work. Be sure to advise patients that the medication is not a substitute for getting adequate sleep.

Shift work sleep disorder is common among persons whose working hours fall between 6 PM and 7 AM. Some night or overnight shift workers cannot stay alert at work or sleep well when off duty, endangering others on the job or while driving.

When shift work sleep disorder is suspected, find out:

• Is the patient getting enough sleep? The average rotating shift worker sleeps 6 hours nightly¹ while working the night shift.
• Is another sleep disorder present? Obstructive sleep apnea, restless legs syndrome, or other common comorbidities may also be disrupting sleep.
• Is an unrecognized comorbid psychiatric disorder present? Not surprisingly, major depression, chemical dependency, and other untreated psychiatric disorders impede adherence to a sleep schedule.
• Is caffeine being used appropriately? Shift workers can effectively use caffeine as an alerting agent but should only use it within 4 to 6 hours after arising. Advise patients against consuming beverages or foods containing caffeine within 8 to 10 hours of bedtime.

Promoting sleep

To help the patient get ample sleep, encourage him or her to:

• find time for uninterrupted sleep. Family time, social events, and errands must be scheduled so that they do not interfere.
• maintain a consistent sleep schedule when possible. Workers with long night shifts should try to stay awake all night and sleep during the day, even on days off.
• use bright lights during waking hours to promote alertness and prevent sleep disruption. Bright light has been shown to influence the human circadian clock.²

Some workplaces are installing artificial lights to increase light exposure during night work. Night shift workers traveling home in the morning should wear sunglasses to limit light exposure.

Also consider prescribing:

• a short-acting hypnotic. Although not specifically FDA-approved for shift work sleep disorder, medications such as zaleplon or zolpidem can reduce time to falling asleep and increase sleep without producing a hangover effect.
• a wakefulness-promoting agent. The FDA recently approved modafinil for reducing excessive daytime sleepiness in shift work sleep disorder. Patients take modafinil, 200 mg/d, shortly after arising to increase alertness at work. Be sure to advise patients that the medication is not a substitute for getting adequate sleep.